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1.  Systemic inflammation and lung function in young adults 
Thorax  2007;62(12):1064-1068.
Background
Impaired lung function is associated with systemic inflammation and is a risk factor for cardiovascular disease in older adults. It is unknown when these associations emerge and to what extent they are mediated by smoking, chronic airways disease, and/or established atherosclerosis. We explored the association between the forced expiratory volume in one second (FEV1) and the systemic inflammatory marker C‐reactive protein (CRP) in young adults.
Methods
Associations between spirometric lung function and blood CRP were assessed in a population based birth cohort of approximately 1000 New Zealanders at ages 26 and 32 years. Analyses adjusted for height and sex to account for differences in predicted lung function and excluded pregnant women.
Results
There were significant inverse associations between FEV1 and CRP at both ages. Similar results were found for the forced vital capacity. These associations were similar in men and women and were independent of smoking, asthma, and body mass index.
Conclusions
Reduced lung function is associated with systemic inflammation in young adults. This association is not related to smoking, asthma, or obesity. The reasons for the association are unexplained, but the findings indicate that the association between lower lung function and increased inflammation predates the development of either chronic lung disease or clinically significant atherosclerosis. The association between poor lung function and cardiovascular disease may be mediated by an inflammatory mechanism.
doi:10.1136/thx.2006.076877
PMCID: PMC2094275  PMID: 17604302
inflammation; C‐reactive protein; spirometry; cohort studies
2.  Accelerated decline in lung function in cigarette smokers is associated with TP53/HDM2 polymorphisms 
Human genetics  2009;126(4):559-565.
In vitro studies have shown that p53 mediates a protective response against DNA damage by causing either cell-cycle arrest and DNA repair, or apoptosis. These responses have not yet been demonstrated in humans. A common source of DNA damage in humans is cigarette smoke, which should activate p53 repair mechanisms. The level of p53 is regulated by HDM2, which targets p53 for degradation. The G-allele of a polymorphism in intron 1 of HDM2 (rs2279744:G/T) results in higher HDM2 levels, and should be associated with a reduced p53 response and hence more DNA damage and corresponding tissue destruction. Similarly, the alleles of a polymorphism (rs1042522) in TP53 that encode arginine (G-allele) or proline (C-allele) at codon 72 cause increased pro-apoptotic (G-allele) or cell-cycle arrest activities (C-allele), respectively, and may moderate p53's ability to prevent DNA damage. To test these hypotheses we examined lung function in relation to cumulative history of smoking in a population-based cohort. The G-alleles in HDM2 and TP53 were found to be associated with accelerated smoking-related decline in lung function. These data support the hypothesis that p53 protects from DNA damage in humans and provides a potential explanation for variation in lung function impairment amongst smokers.
doi:10.1007/s00439-009-0704-z
PMCID: PMC3740961  PMID: 19521721
3.  The Christmas season as a risk factor for chronic obstructive pulmonary disease exacerbations 
BACKGROUND
Epidemics of hospitalization for chronic obstructive pulmonary disease (COPD) occur annually during the Christmas holidays, and COPD exacerbations commonly coincide with respiratory viral infections.
OBJECTIVE
To compare the incidence and determinants of COPD exacerbations occurring between the Christmas holiday period and the remainder of the winter season.
METHODS
Seventy-one subjects with COPD of mixed severity faxed daily symptom diaries to a computer monitoring system from December 1, 2006, to April 30, 2007. Possible exacerbations prompted a home visit for assessment, spirometry and specimen collection for virological testing.
RESULTS
Study subjects submitted a total of 95.4% of possible daily symptom diary sheets by fax. Of 114 possible COPD exacerbations detected using the faxed diaries, 110 met the Anthonisen criteria for true exacerbations. A total of 47 exacerbations (mean 6.7/week) occurred during the Christmas holiday period, while 63 exacerbations (mean 4.3/week) occurred during the remainder of winter. Of the Christmas period exacerbations and of those in the balance of winter, 21 (44%) and 20 (32%), respectively, coincided with respiratory viral infections.
CONCLUSIONS
The incidence of COPD exacerbations during the Christmas period was greater than during the rest of winter in 2006/2007 and peaked immediately before Christmas – in contrast to hospital presentation for COPD, which peaked during the Christmas week. No clear role of respiratory viral infections in the increased rate of exacerbations during the Christmas period was established in the present study. COPD patients were highly compliant with daily symptom reporting using faxed daily diaries, which permitted nearly complete detection of all exacerbations that occurred at incidence.
PMCID: PMC3006150  PMID: 21165349
Christmas; COPD; Epidemiology; Respiratory viruses
4.  Prevalence of asthma among Chinese adolescents living in Canada and in China 
Background
Studies of the prevalence of asthma among migrating populations may help in identifying environmental risk factors.
Methods
We analyzed data from Vancouver, Canada, and from Guangzhou, Beijing and Hong Kong, China, collected during phase 3 of the International Study of Asthma and Allergies in Childhood. We subdivided the Vancouver adolescents according to whether they were Chinese immigrants to Canada, Canadian-born Chinese or Canadian-born non-Chinese. We compared the prevalence of asthma and wheezing among Chinese adolescents born in Canada, Chinese adolescents who had immigrated to Canada and Chinese adolescents living in China.
Results
Of 7794 Chinese adolescents who met the inclusion criteria, 3058 were from Guangzhou, 2824 were from Beijing, and 1912 were from Hong Kong. Of 2235 adolescents in Vancouver, Canada, 475 were Chinese immigrants, 617 were Canadian-born Chinese, and 1143 were Canadian-born non-Chinese. The prevalence of current wheezing among boys ranged from 5.9% in Guangzhou to 11.2% in Canadian-born Chinese adolescents. For girls, the range was 4.3% in Guangzhou to 9.8% in Canadian-born Chinese adolescents. The prevalence of ever having had asthma ranged from 6.6% to 16.6% for boys and from 2.9% to 15.0% for girls. Prevalence gradients persisted after adjustment for other environmental variables (odds ratios for ever having had asthma among Canadian-born Chinese compared with native Chinese in Guangzhou: 2.72 [95% confidence interval 1.75–4.23] for boys and 5.50 [95% confidence interval 3.21–9.44] for girls; p < 0.001 for both). Among Chinese adolescents living in Vancouver, the prevalence of ever wheezing increased with duration of residence, from 14.5% among those living in Canada for less than 7 years to 20.9% among those living their entire life in Canada. The same pattern was observed for the prevalence of ever having had asthma, from 7.7% to 15.9%.
Interpretation
Asthma symptoms in Chinese adolescents were lowest among residents of mainland China, were greater for those in Hong Kong and those who had immigrated to Canada, and were highest among those born in Canada. These findings suggest that environmental factors and duration of exposure influence asthma prevalence.
doi:10.1503/cmaj.071797
PMCID: PMC2582762  PMID: 19015564
5.  Factors affecting exhaled nitric oxide measurements: the effect of sex 
Respiratory Research  2007;8(1):82.
Background
Exhaled nitric oxide (FENO) measurements are used as a surrogate marker for eosinophilic airway inflammation. However, many constitutional and environmental factors affect FENO, making it difficult to devise reference values. Our aim was to evaluate the relative importance of factors affecting FENO in a well characterised adult population.
Methods
Data were obtained from 895 members of the Dunedin Multidisciplinary Health and Development Study at age 32. The effects of sex, height, weight, lung function indices, smoking, atopy, asthma and rhinitis on FENO were explored by unadjusted and adjusted linear regression analyses.
Results
The effect of sex on FENO was both statistically and clinically significant, with FENO levels approximately 25% less in females. Overall, current smoking reduced FENO up to 50%, but this effect occurred predominantly in those who smoked on the day of the FENO measurement. Atopy increased FENO by 60%. The sex-related differences in FENO remained significant (p < 0.001) after controlling for all other significant factors affecting FENO.
Conclusion
Even after adjustment, FENO values are significantly different in males and females. The derivation of reference values and the interpretation of FENO in the clinical setting should be stratified by sex. Other common factors such as current smoking and atopy also require to be taken into account.
doi:10.1186/1465-9921-8-82
PMCID: PMC2231356  PMID: 18005450
6.  Associations between respiratory symptoms, lung function and gastro-oesophageal reflux symptoms in a population-based birth cohort 
Respiratory Research  2006;7(1):142.
Background
Several studies have reported an association between asthma and gastro-oesophageal reflux, but it is unclear which condition develops first. The role of obesity in mediating this association is also unclear. We explored the associations between respiratory symptoms, lung function, and gastro-oesophageal reflux symptoms in a birth cohort of approximately 1000 individuals.
Methods
Information on respiratory symptoms, asthma, atopy, lung function and airway responsiveness was obtained at multiple assessments from childhood to adulthood in an unselected birth cohort of 1037 individuals followed to age 26. Symptoms of gastro-oesophageal reflux and irritable bowel syndrome were recorded at age 26.
Results
Heartburn and acid regurgitation symptoms that were at least "moderately bothersome" at age 26 were significantly associated with asthma (odds ratio = 3.2; 95% confidence interval = 1.6–6.4), wheeze (OR = 3.5; 95% CI = 1.7–7.2), and nocturnal cough (OR = 4.3; 95% CI = 2.1–8.7) independently of body mass index. In women reflux symptoms were also associated with airflow obstruction and a bronchodilator response to salbutamol. Persistent wheezing since childhood, persistence of asthma since teenage years, and airway hyperresponsiveness since age 11 were associated with a significantly increased risk of heartburn and acid regurgitation at age 26. There was no association between irritable bowel syndrome and respiratory symptoms.
Conclusion
Reflux symptoms are associated with respiratory symptoms in young adults independently of body mass index. The mechanism of these associations remains unclear.
doi:10.1186/1465-9921-7-142
PMCID: PMC1702357  PMID: 17147826
7.  Sex Differences in Factors Associated with Childhood- and Adolescent-Onset Wheeze 
Rationale: Factors predicting the development of wheeze may differ between sexes and between childhood and adolescence. Methods: A New Zealand birth cohort of 1,037 children was followed to age 26. For this analysis, those reporting recurrent wheezing at two or more assessments were classified as “wheezers.” We examined risk factors for development of wheeze before age 10 (childhood) and subsequently (adolescent-onset) for males and for females separately using Cox regression modeling. Results: Males more often developed childhood wheeze (p = 0.002) and females adolescent-onset wheeze (p < 0.001). Maternal atopy (asthma or hay fever) was a risk factor for childhood wheeze in both sexes (hazard ratio [HR], 1.48, p < 0.05 for males; HR, 2.37, p < 0.001 for females). Paternal atopy also influenced childhood wheeze, significantly for males (HR, 1.72; p = 0.01), and similarly but not significantly for females (HR, 1.70; p = 0.08). For adolescent-onset wheeze, neither maternal (HR, 1.41; p = 0.19) nor paternal history (HR, 0.73; p = 0.42) was a risk factor in males, but maternal history (HR, 2.08; p < 0.01) was a significant risk factor for females. When both age ranges were combined, providing greater power for analysis, paternal history was a stronger risk factor for wheeze in females (HR, 1.62; p = 0.02) than in males (HR, 1.35; p = 0.12). Conclusion: The influence of parental atopy on the development for wheeze differs between males and females and between childhood- and adolescent-onset wheeze.
doi:10.1164/rccm.200412-1738OC
PMCID: PMC2718447  PMID: 15805179
age of onset; asthma; parental history; risk factors; sex

Results 1-7 (7)