Search tips
Search criteria

Results 1-8 (8)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
1.  Systemic inflammation and decline in lung function in a general population: a prospective study 
Thorax  2007;62(6):515-520.
An increase in levels of C‐reactive protein (CRP), a marker of systemic inflammation, is associated with reduced forced expiratory volume in 1 s (FEV1), supporting the hypothesis that the pathophysiology of chronic obstructive pulmonary disease has a systemic inflammatory component. However, few large studies have assessed the relationship between systemic inflammation as measured by CRP and decline in lung function prospectively in a randomly selected population.
In 1991, data were collected on FEV1 and forced vital capacity (FVC) and a blood sample was taken from 2442 randomly selected adults in a community‐based cohort. In 2000 these measures were repeated in 1301 individuals. The level of serum CRP was analysed in these samples from 1991 and 2000.
In cross‐sectional analyses of data from 1991 and 2000, serum CRP levels were inversely related to FEV1 and FVC. After adjustment for smoking and other confounders, the difference in FEV1 was reduced by −9 ml (95% CI –13 to –5) and –7 ml (95% CI –13 to –2) for each mg/l increment in serum CRP in 1991 and 2000, respectively. There was no significant association between baseline serum CRP levels and decline in FEV1 and FVC over 9 years.
Although serum CRP levels are inversely associated with lung function in cross‐sectional studies, there was no effect of a marker of systemic inflammation on decline in lung function over 9 years.
PMCID: PMC2117221  PMID: 17251312
2.  Cardiovascular and inflammatory effects of simvastatin therapy in patients with COPD: a randomized controlled trial 
There is excess cardiovascular mortality in patients with chronic obstructive pulmonary disease. Aortic stiffness, an independent predictor of cardiovascular risk, and systemic and airway inflammation are increased in patients with the disease. Statins modulate aortic stiffness and have anti-inflammatory properties. A proof-of-principle, double-blind, randomized trial determined if 6 weeks of simvastatin 20 mg once daily reduced aortic stiffness and systemic and airway inflammation in patients with chronic obstructive pulmonary disease.
Stable patients (n=70) were randomized to simvastatin (active) or placebo. Pre-treatment and post-treatment aortic stiffness, blood pressure, spirometry, and circulating and airway inflammatory mediators and lipids were measured. A predefined subgroup analysis was performed where baseline aortic pulse wave velocity (PWV) was >10 m/sec.
Total cholesterol dropped in the active group. There was no significant change in aortic PWV between the active group and the placebo group (−0.7 m/sec, P=0.24). In those with aortic stiffness >10 m/sec (n=22), aortic PWV improved in the active group compared with the placebo group (−2.8 m/sec, P=0.03). Neither systemic nor airway inflammatory markers changed.
There was a nonsignificant improvement in aortic PWV in those taking simvastatin 20 mg compared with placebo, but in those with higher baseline aortic stiffness (a higher risk group) a significant and clinically relevant reduction in PWV was shown.
PMCID: PMC4321645
chronic obstructive pulmonary disease; arterial stiffness; statins
3.  Rate of improvement of CF life expectancy exceeds that of general population—Observational death registration study☆☆☆ 
Journal of Cystic Fibrosis  2014;13(4):410-415.
It is unclear why cystic fibrosis (CF) survival has improved. We wished to quantify increases in CF median age of death in the context of general population survival improvement.
Death registration data analysis (US, England & Wales (E&W)—1972–2009).
CF median age of death is higher in US than E&W and greater for males, opposite to that of death from all causes. CF median age of death has increased by 0.543 life years per year (E&W, US combined (95% confidence interval 0.506, 0.582)). The difference in median age at death between those dying from all causes and CF decreased in both territories. CF median age of death for males is greater than for females in both territories. This gap has not narrowed.
The median age of death of people with CF is improving more rapidly than that of the general population in US and E&W.
PMCID: PMC4074348  PMID: 24418187
Cystic fibrosis; Survival; Mortality; Healthcare
4.  Effect of Five Genetic Variants Associated with Lung Function on the Risk of Chronic Obstructive Lung Disease, and Their Joint Effects on Lung Function 
Rationale: Genomic loci are associated with FEV1 or the ratio of FEV1 to FVC in population samples, but their association with chronic obstructive pulmonary disease (COPD) has not yet been proven, nor have their combined effects on lung function and COPD been studied.
Objectives: To test association with COPD of variants at five loci (TNS1, GSTCD, HTR4, AGER, and THSD4) and to evaluate joint effects on lung function and COPD of these single-nucleotide polymorphisms (SNPs), and variants at the previously reported locus near HHIP.
Methods: By sampling from 12 population-based studies (n = 31,422), we obtained genotype data on 3,284 COPD case subjects and 17,538 control subjects for sentinel SNPs in TNS1, GSTCD, HTR4, AGER, and THSD4. In 24,648 individuals (including 2,890 COPD case subjects and 13,862 control subjects), we additionally obtained genotypes for rs12504628 near HHIP. Each allele associated with lung function decline at these six SNPs contributed to a risk score. We studied the association of the risk score to lung function and COPD.
Measurements and Main Results: Association with COPD was significant for three loci (TNS1, GSTCD, and HTR4) and the previously reported HHIP locus, and suggestive and directionally consistent for AGER and TSHD4. Compared with the baseline group (7 risk alleles), carrying 10–12 risk alleles was associated with a reduction in FEV1 (β = –72.21 ml, P = 3.90 × 10−4) and FEV1/FVC (β = –1.53%, P = 6.35 × 10−6), and with COPD (odds ratio = 1.63, P = 1.46 × 10−5).
Conclusions: Variants in TNS1, GSTCD, and HTR4 are associated with COPD. Our highest risk score category was associated with a 1.6-fold higher COPD risk than the population average score.
PMCID: PMC3398416  PMID: 21965014
FEV1; FVC; genome-wide association study; modeling risk
5.  The Association Between Blood Coagulation Activity and Lung Function: A Population-Based Study 
PLoS ONE  2010;5(11):e15014.
Increased in susceptibility to thrombotic disease may be associated with lower lung function. If causal, this association may suggest an area for development of new interventions for lung disease. The aim of this study was to investigate the association between blood coagulation activation as measured by plasma d-dimers and lung function.
Methodology/Principal Findings
We conducted a cross-sectional study on 2463 randomly selected adults in 1991 and followed up 1252 of these individuals in 2000. Plasma D-dimer levels, a marker of activity of blood coagulation pathways, were analysed in the baseline 1991 samples. There was an inverse cross-sectional association between plasma D-dimer and Forced Expiratory Volume in one second, with a decrease of 71 ml per µg FEU/ml increment in plasma D-dimer (95% confidence intervals CI: −135 to −6), and a decrease in Forced Vital Capacity (97 ml per µg FEU/ml increase in D-dimer, 95%CI: −170 to −24). These associations were attenuated after adjustment for serum highly sensitive CRP. No association was observed between plasma D-dimer and the decline in lung function between 1991 and 2000.
The cross-sectional findings are consistent with the hypothesis that activation of blood coagulation pathways is associated with decreased lung function, and that systemic inflammation may contribute to this relation. However, the lack of an association with decline in lung function suggests that clotting pathways that involve d-dimers may not be a promising therapeutic target for new interventions for respiratory disease.
PMCID: PMC2982817  PMID: 21103357
6.  Genome-wide association study identifies five loci associated with lung function 
Repapi, Emmanouela | Sayers, Ian | Wain, Louise V | Burton, Paul R | Johnson, Toby | Obeidat, Ma’en | Zhao, Jing Hua | Ramasamy, Adaikalavan | Zhai, Guangju | Vitart, Veronique | Huffman, Jennifer E | Igl, Wilmar | Albrecht, Eva | Deloukas, Panos | Henderson, John | Granell, Raquel | McArdle, Wendy L | Rudnicka, Alicja R | Barroso, Inês | Loos, Ruth J F | Wareham, Nicholas J | Mustelin, Linda | Rantanen, Taina | Surakka, Ida | Imboden, Medea | Wichmann, H Erich | Grkovic, Ivica | Jankovic, Stipan | Zgaga, Lina | Hartikainen, Anna-Liisa | Peltonen, Leena | Gyllensten, Ulf | Johansson, Åsa | Zaboli, Ghazal | Campbell, Harry | Wild, Sarah H | Wilson, James F | Gläser, Sven | Homuth, Georg | Völzke, Henry | Mangino, Massimo | Soranzo, Nicole | Spector, Tim D | Polašek, Ozren | Rudan, Igor | Wright, Alan F | Heliövaara, Markku | Ripatti, Samuli | Pouta, Anneli | Naluai, Åsa Torinsson | Olin, Anna-Carin | Torén, Kjell | Cooper, Matthew N | James, Alan L | Palmer, Lyle J | Hingorani, Aroon D | Wannamethee, S Goya | Whincup, Peter H | Smith, George Davey | Ebrahim, Shah | McKeever, Tricia M | Pavord, Ian D | MacLeod, Andrew K | Morris, Andrew D | Porteous, David J | Cooper, Cyrus | Dennison, Elaine | Shaheen, Seif | Karrasch, Stefan | Schnabel, Eva | Schulz, Holger | Grallert, Harald | Bouatia-Naji, Nabila | Delplanque, Jérôme | Froguel, Philippe | Blakey, John D | Britton, John R | Morris, Richard W | Holloway, John W | Lawlor, Debbie A | Hui, Jennie | Nyberg, Fredrik | Jarvelin, Marjo-Riitta | Jackson, Cathy | Kähönen, Mika | Kaprio, Jaakko | Probst-Hensch, Nicole M | Koch, Beate | Hayward, Caroline | Evans, David M | Elliott, Paul | Strachan, David P | Hall, Ian P | Tobin, Martin D
Nature genetics  2009;42(1):36-44.
Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n ≤ 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n ≤ 883). We confirmed the reported locus at 4q31 and identified associations with FEV1 or FEV1/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 × 10−12), 4q24 in GSTCD (2.18 × 10−23), 5q33 in HTR4 (P = 4.29 × 10−9), 6p21 in AGER (P = 3.07 × 10−15) and 15q23 in THSD4 (P = 7.24 × 10−15). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.
PMCID: PMC2862965  PMID: 20010834
7.  A multivariate analysis of serum nutrient levels and lung function 
Respiratory Research  2008;9(1):67.
There is mounting evidence that estimates of intakes of a range of dietary nutrients are related to both lung function level and rate of decline, but far less evidence on the relation between lung function and objective measures of serum levels of individual nutrients. The aim of this study was to conduct a comprehensive examination of the independent associations of a wide range of serum markers of nutritional status with lung function, measured as the one-second forced expiratory volume (FEV1).
Using data from the Third National Health and Nutrition Examination Survey, a US population-based cross-sectional study, we investigated the relation between 21 serum markers of potentially relevant nutrients and FEV1, with adjustment for potential confounding factors. Systematic approaches were used to guide the analysis.
In a mutually adjusted model, higher serum levels of antioxidant vitamins (vitamin A, beta-cryptoxanthin, vitamin C, vitamin E), selenium, normalized calcium, chloride, and iron were independently associated with higher levels of FEV1. Higher concentrations of potassium and sodium were associated with lower FEV1.
Maintaining higher serum concentrations of dietary antioxidant vitamins and selenium is potentially beneficial to lung health. In addition other novel associations found in this study merit further investigation.
PMCID: PMC2565672  PMID: 18823528
8.  What characteristics of primary care and patients are associated with early death in patients with lung cancer in the UK? 
Thorax  2014;70(2):161-168.
The UK has poor lung cancer survival rates and high early mortality, compared to other countries. We aimed to identify factors associated with early death, and features of primary care that might contribute to late diagnosis.
All cases of lung cancer diagnosed between 2000 and 2013 were extracted from The Health Improvement Network database. Patients who died within 90 days of diagnosis were compared with those who survived longer. Standardised chest X-ray (CXR) and lung cancer rates were calculated for each practice.
Of 20 142 people with lung cancer, those who died early consulted with primary care more frequently prediagnosis. Individual factors associated with early death were male sex (OR 1.17; 95% CI 1.10 to 1.24), current smoking (OR 1.43; 95% CI 1.28 to 1.61), increasing age (OR 1.80; 95% CI 1.62 to 1.99 for age ≥80 years compared to 65–69 years), social deprivation (OR 1.16; 95% CI 1.04 to 1.30 for Townsend quintile 5 vs 1) and rural versus urban residence (OR 1.22; 95% CI 1.06 to 1.41). CXR rates varied widely, and the odds of early death were highest in the practices which requested more CXRs. Lung cancer incidence at practice level did not affect early deaths.
Patients who die early from lung cancer are interacting with primary care prediagnosis, suggesting potentially missed opportunities to identify them earlier. A general increase in CXR requests may not improve survival; rather, a more timely and appropriate targeting of this investigation using risk assessment tools needs further assessment.
PMCID: PMC4316923  PMID: 25311471
Lung Cancer; Clinical Epidemiology

Results 1-8 (8)