Associations of interleukin-1 gene cluster polymorphisms with C-reactive protein concentration and lung function decline in smoking-induced chronic obstructive pulmonary disease.

Objective: We reported association of haplotypes formed by IL-1b (IL1B)-511C/T (rs16944) and a variable number of tandem repeats (rs2234663) in intron 3 of IL-1 receptor antagonist (IL1RN) with rate of lung function decline in smoking-induced COPD. The aim of current study was to further investigate this association.

Methods: We genotyped an additional 19 polymorphisms in IL1 cluster (including IL1A, IL1B and IL1RN) in non-Hispanic whites who had the fastest (n = 268) and the slowest (n = 292) decline of FEV1% predicted in the same study.

NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease.

An oxidant-antioxidant imbalance in the lung contributes to the development of chronic obstructive pulmonary disease (COPD) that is caused by a complex interaction of genetic and environmental risk factors. Nuclear erythroid 2-related factor 2 (NFE2L2 or NRF2) is a critical molecule in the lung's defense mechanism against oxidants. We investigated whether polymorphisms in the NFE2L2 pathway affected the rate of decline of lung function in smokers from the Lung Health Study (LHS)(n = 547) and in a replication set, the Vlagtwedde-Vlaardingen cohort (n = 533).

The relationship between telomere length and mortality in chronic obstructive pulmonary disease (COPD).

Some have suggested that chronic obstructive pulmonary disease (COPD) is a disease of accelerated aging. Aging is characterized by shortening of telomeres. The relationship of telomere length to important clinical outcomes such as mortality, disease progression and cancer in COPD is unknown.

Influence of lightweight ambulatory oxygen on oxygen use and activity patterns of COPD patients receiving long-term oxygen therapy.

Lightweight ambulatory oxygen devices are provided on the assumptions that they enhance compliance and increase activity, but data to support these assumptions are lacking. We studied 22 patients with severe chronic obstructive pulmonary disease receiving long-term oxygen therapy (14 men, average age = 66.9 y, FEV(1) = 33.

Effect of heme oxygenase-1 polymorphisms on lung function and gene expression.

Background: Oxidative stress induced by smoking is considered to be important in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). Heme oxygenase-1 (HMOX1) is an essential enzyme in heme catabolism that is induced by oxidative stress and may play a protective role as an antioxidant in the lung. We determined whether HMOX1 polymorphisms were associated with lung function in COPD patients and whether the variants had functional effects.

Azithromycin for prevention of exacerbations of COPD.

Background: Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease (COPD). Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases.

Methods: We performed a randomized trial to determine whether azithromycin decreased the frequency of exacerbations in participants with COPD who had an increased risk of exacerbations but no hearing impairment, resting tachycardia, or apparent risk of prolongation of the corrected QT interval.

Effect of gene environment interactions on lung function and cardiovascular disease in COPD.

Background: The objective of this study was to determine if gene-environment interactions between cigarette smoking and interleukin-6 (IL6), interferon-γ (IFNG), interleukin-1β (IL1B), or interleukin-1 receptor antagonist (IL1RN) single nucleotide polymorphisms are associated with lung function decline and cardiovascular disease in chronic obstructive pulmonary disease (COPD).

Methods: Single nucleotide polymorphisms (SNPs) in IL6, IFNG, IL1B, and IL1RN were genotyped in the Lung Health Study and correlated with rate of decline of forced expiratory volume in 1 second (FEV(1)) over 5 years, baseline FEV(1), serum protein levels, cardiovascular disease, and interactions with smoking.

Results: The IL6 rs2069825 single nucleotide polymorphism was associated with the rate of decline of prebronchodilator FEV(1) (P = 0.

Superior immune response to protein-conjugate versus free pneumococcal polysaccharide vaccine in chronic obstructive pulmonary disease.

Rationale: Debate exists about the immunogenicity and protective efficacy of antibodies produced by the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in chronic obstructive pulmonary disease (COPD). The 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) induces a more robust immune response than PPSV23 in healthy elderly adults.

Objectives: We hypothesized that serotype-specific IgG antibody concentration and functional antibody activity would be superior after PCV7 vaccination compared with PPSV23 in moderate to severe COPD.

Efficacy of esomeprazole for treatment of poorly controlled asthma.

Background: Gastroesophageal reflux is common among patients with asthma but often causes mild or no symptoms. It is not known whether treatment of gastroesophageal reflux with proton-pump inhibitors in patients who have poorly controlled asthma without symptoms of gastroesophageal reflux can substantially improve asthma control.

Methods: In a parallel-group, double-blind trial, we randomly assigned 412 participants with inadequately controlled asthma, despite treatment with inhaled corticosteroids, and with minimal or no symptoms of gastroesophageal reflux to receive either 40 mg of esomeprazole twice a day or matching placebo.

Airflow obstruction in young adults in Canada.

Objective: Airflow obstruction is relatively uncommon in young adults, and may indicate potential for the development of progressive disease. The objective of the present study was to enumerate and characterize airflow obstruction in a random sample of Canadians aged 20 to 44 years.

Setting: The sample (n=2962) was drawn from six Canadian sites.

Transforming growth factor-beta1 polymorphisms, airway responsiveness and lung function decline in smokers.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the airways, parenchyma and vessels, which can cause a structural remodeling with increased fibrosis that narrows and fixes the airway lumen. Transforming growth factor-beta1 (TGF-beta1), a multifunctional growth factor, was reported to be increased in the airways of COPD patients. In this study, we hypothesized that polymorphisms in the TGF-beta1 gene would be associated with an accelerated rate of decline of forced expiratory volume in 1s (FEV(1)).

Association of Hck genetic polymorphisms with gene expression and COPD.

Polymorphonuclear leukocytes (PMNs) are major effector cells in the chronic airway inflammation in chronic obstructive pulmonary disease (COPD). PMN degranulation is associated with degradation of extracellular matrix and tissue damage. Hck is an essential molecule in the signaling pathway regulating PMN degranulation.

Inhaled corticosteroids and mortality in COPD.

Study Objectives: To assess the influence of inhaled corticosteroids (ICSs) on mortality in COPD patients, which is currently a controversial topic.

Setting: Manitoba Health maintains a population-wide research database that includes pharmaceutical information.

Design And Patients: We examined mortality in people 90 to 365 days after hospital discharge for COPD, comparing those persons who received inhaled steroids within 90 days of hospital discharge with those who did not.

Contribution of alpha- and beta-defensins to lung function decline and infection in smokers: an association study.

Background: Alpha-defensins, which are major constituents of neutrophil azurophilic granules, and beta-defensins, which are expressed in airway epithelial cells, could contribute to the pathogenesis of chronic obstructive pulmonary disease by amplifying cigarette smoke-induced and infection-induced inflammatory reactions leading to lung injury. In Japanese and Chinese populations, two different beta-defensin-1 polymorphisms have been associated with chronic obstructive pulmonary disease phenotypes. We conducted population-based association studies to test whether alpha-defensin and beta-defensin polymorphisms influenced smokers' susceptibility to lung function decline and susceptibility to lower respiratory infection in two groups of white participants in the Lung Health Study (275 = fast decline in lung function and 304 = no decline in lung function).

Interferon gamma polymorphisms and their interaction with smoking are associated with lung function.

Interactions between genetic and environmental determinants are likely to be important in the pathogenesis of chronic obstructive pulmonary disease. We hypothesized that interferon gamma (IFNG) single nucleotide polymorphisms (SNPs) and their interaction with smoking are associated with the rate of decline or level of lung function in smokers. We studied four SNPs in IFNG in 585 non-Hispanic whites (NHW) who had the fastest (n =280) or the slowest (n=305) decline of FEV(1)% predicted selected from among continuous smokers followed for 5 years in the NHLBI Lung Health Study.

Physician-diagnosed asthma and allergic rhinitis in Manitoba: 1985-1998.

Background: A worldwide increase has been noted in the prevalence of asthma, but the data for other allergic disorders are less consistent.

Objective: To study 14-year trends in utilization of physician resources for asthma and compare them to trends for allergic rhinitis.

Methods: We studied visits to physicians by Manitoba residents for asthma (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 493) and allergic rhinitis (ICD-9 code 477) between 1985 and 1998.

Lack of association of human leukocyte antigen-B7 with COPD and rate of decline in lung function.

Background: Although variation in the human leukocyte antigen (HLA) locus is associated with various diseases, there have been a limited number of studies that have examined the possible role of HLA in chronic obstructive pulmonary disease (COPD). Only HLA-B7 has been shown to be correlated with low forced expiratory volume in 1s (FEV1) in Caucasians; however, this finding has not been replicated. The aim of this study was to investigate the contribution of the HLA-B7 allele to COPD and to rate of decline of lung function.

The effects of a smoking cessation intervention on 14.5-year mortality: a randomized clinical trial.

Background: Randomized clinical trials have not yet demonstrated the mortality benefit of smoking cessation.

Objective: To assess the long-term effect on mortality of a randomly applied smoking cessation program.

Design: The Lung Health Study was a randomized clinical trial of smoking cessation.

Risk of physician-diagnosed asthma in the first 6 years of life.

Objective: The objective of this cohort study was to determine if complications of pregnancy and labor, characteristics at birth, and exposure to infections influence the incidence of asthma in the first 6 years of life.

Design: We identified all children born between 1980 and 1990 in the Province of Manitoba, Canada. We used records of physician contacts (inpatient and outpatient) and services of the universal provincial health insurance plan to follow up 170,960 children from birth to the age of 6 years to identify the first diagnosis of asthma.

Glutathione S-transferase variants and their interaction with smoking on lung function.

We studied glutathione S-transferase (GST) polymorphisms in 1,098 whites with the lowest (n = 544, FEV(1) % predicted mean +/- SEM = 62.6 +/- 0.1) and the highest (n = 554, FEV(1) % predicted mean +/- SEM = 91.

Geographic and gender variability in the prevalence of bronchial responsiveness in Canada.

Objectives: Geographic variability in reported prevalences of asthma worldwide could in part relate to interpretation of symptoms and diagnostic biases. Bronchial responsiveness measurements provide objective evidence of a common physiologic characteristic of asthma. We measured bronchial responsiveness using the standardized protocol of the European Community Respiratory Health Survey (ECRHS) in six sites in Canada, and compared prevalences across Canada with international sites.

Polymorphisms in the IL13, IL13RA1, and IL4RA genes and rate of decline in lung function in smokers.

Targeted expression of interleukin (IL)-13 in the adult murine lung has been shown to cause emphysema. We hypothesized that variants in the IL13, IL13RA1, and IL4RA genes would be associated with an accelerated rate of decline of lung function among smokers. We determined the allele frequencies of five polymorphisms in the IL13, IL13RA1, and IL4RA genes in 588 continuing smokers chosen from the NHLBI Lung Health Study for having the fastest (n = 282) and slowest (n = 306) 5-yr rate of decline of lung function (mean change in FEV(1) %predicted/yr = -4.

Diagnosing asthma: the fit between survey and administrative database.

Background: Standard methods for population studies of asthma include surveying population samples using questionnaires and examining people in laboratories. These procedures are extremely expensive. It would be helpful if, at least for some purposes, they could be replaced by cheaper techniques with adequate validity.

Persistence of the effect of the Lung Health Study (LHS) smoking intervention over eleven years.

Background: Research on the long-term persistence of effects of interventions aimed at smoking cessation is limited. This paper examined the quitting behavior of individuals who were randomized to a smoking cessation intervention (SI) or to usual care (UC), at a point approximately 11 years later.

Methods: The initial sample consisted of 5,887 adult smokers in 10 clinics who had evidence of airways obstruction.