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1.
Eur Respir J ; 49(4)2017 04.
Article in English | MEDLINE | ID: mdl-28404647

ABSTRACT

Guidelines on spontaneous pneumothorax are contradictory as to intervention between needle aspiration (NA) and chest tube drainage (CTD). Studies show poor adherence to guidelines.Three Norwegian hospitals included patients with primary (PSP) and secondary (SSP) spontaneous pneumothorax. Patients underwent NA or CTD as the primary intervention. The main outcome was duration of hospital stay. Secondary outcomes were immediate- and 1-week success rates and complications.127 patients were included, including 48 patients with SSP. 65 patients underwent NA, 63 patients CTD. Median (interquartile range) hospital stay was significantly shorter for NA: 2.4 days (1.2-4.7 days), compared with CTD: 4.6 days (2.3-7.8 days) (p<0.001). The corresponding figures for the SSP subgroup were 2.54 days (1.17-7.79 days) compared with 5.53 days (3.65-9.21 days) (p=0.049) for NA and CTD, respectively. Immediate success rates were 69% for NA compared with 32% for CTD (p<0.001). The positive effect of NA remained significant in sub-analyses for SSP. There was no significant difference in 1-week success rates. Complications occurred only during the CTD-treatment.Our study shows shorter hospital stay and higher immediate success rates for NA compared with CTD. Subgroup analyses also show clear benefits for NA for both PSP and SSP.


Subject(s)
Drainage , Pneumothorax/surgery , Postoperative Complications/epidemiology , Suction/methods , Adult , Chest Tubes , Female , Humans , Kaplan-Meier Estimate , Length of Stay , Male , Middle Aged , Needles , Norway , Young Adult
2.
Respir Med ; 115: 53-9, 2016 06.
Article in English | MEDLINE | ID: mdl-27215504

ABSTRACT

BACKGROUND: COPD patients are advised vaccination against seasonal influenza, yet few studies have evaluated the protective antibody titers obtained in this patient group. AIMS: 1) To describe protective titers in COPD patients who self-reported influenza vaccination compared with vaccinated subjects without COPD and unvaccinated COPD patients, 2) analyze whether clinical parameters predicted influenza-specific antibody titers, and 3) whether antibody titers to influenza A at baseline could predict exacerbation risk or 5 years all-cause mortality. METHODS: Influenza A (H1N1 and H3N2) titers were measured by haemagglutination inhibition assay in serum from 432 COPD patients and 77 controls in the Bergen COPD Cohort Study, at yearly visits between 2006/09. Titers of 40 or above were considered protective. We examined the variables sex, age, body composition, smoking, GOLD stage, yearly exacerbations, inhaled steroids, and Charlson score as predictive of titers, both univariately and in a multivariable model estimated by generalized estimating equations. The exacerbation incidence rate ratios and mortality hazard ratios were assessed by negative binominal and cox regression models respectively. RESULTS: At baseline, 59% of COPD patients reported influenza vaccination during the last season. Levels of predictive titers varied considerably each season, but trended lower in COPD patients compared with controls. Neither sex, age, body composition, smoking, comorbidities, GOLD stage nor use of inhaled steroids consistently predicted titers. Having high titers at baseline did not impact later risk for exacerbations, but seemed to be associated with higher all-cause mortality, even after adjustment for COPD disease characteristics. CONCLUSION: Vaccination coverage for influenza is imperfect for COPD patients in Norway, and there is a concern that immunization is suboptimal.


Subject(s)
Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Pulmonary Disease, Chronic Obstructive/immunology , Self Report , Vaccination/methods , Adult , Aged , Antibodies, Viral/blood , Cohort Studies , Comorbidity , Female , Hemagglutination Inhibition Tests/methods , Humans , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H3N2 Subtype/immunology , Influenza Vaccines/immunology , Influenza, Human/epidemiology , Influenza, Human/therapy , Influenza, Human/virology , Male , Middle Aged , Mortality , Norway/epidemiology , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Seasons , Smoking/immunology , Vaccination/adverse effects
3.
Pharmacogenomics J ; 16(4): 326-35, 2016 08.
Article in English | MEDLINE | ID: mdl-26503814

ABSTRACT

Short-acting ß2-agonist bronchodilators are the most common medications used in treating chronic obstructive pulmonary disease (COPD). Genetic variants determining bronchodilator responsiveness (BDR) in COPD have not been identified. We performed a genome-wide association study (GWAS) of BDR in 5789 current or former smokers with COPD in one African-American and four white populations. BDR was defined as the quantitative spirometric response to inhaled ß2-agonists. We combined results in a meta-analysis. In the meta-analysis, single-nucleotide polymorphisms (SNPs) in the genes KCNK1 (P=2.02 × 10(-7)) and KCNJ2 (P=1.79 × 10(-7)) were the top associations with BDR. Among African Americans, SNPs in CDH13 were significantly associated with BDR (P=5.1 × 10(-9)). A nominal association with CDH13 was identified in a gene-based analysis in all subjects. We identified suggestive association with BDR among COPD subjects for variants near two potassium channel genes (KCNK1 and KCNJ2). SNPs in CDH13 were significantly associated with BDR in African Americans.The Pharmacogenomics Journal advance online publication, 27 October 2015; doi:10.1038/tpj.2015.65.


Subject(s)
Adrenergic beta-2 Receptor Agonists/therapeutic use , Bronchodilator Agents/therapeutic use , Lung/drug effects , Pharmacogenomic Variants/genetics , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/genetics , Black or African American/genetics , Aged , Cadherins/genetics , Europe , Female , Genome-Wide Association Study , Genotype , Humans , Lung/physiopathology , Male , Middle Aged , New Zealand , North America , Pharmacogenomic Testing , Phenotype , Potassium Channels, Inwardly Rectifying/genetics , Potassium Channels, Tandem Pore Domain/genetics , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Risk Factors , Sarcoglycans/genetics , Severity of Illness Index , Spirometry , Treatment Outcome , White People/genetics
4.
Public Health ; 129(2): 155-61, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25682903

ABSTRACT

OBJECTIVE: To determine whether the sense of coherence (SOC) could predict the outcome of an 18-month lifestyle intervention program for subjects at risk of type 2 diabetes. METHODS: Subjects at high risk of type 2 diabetes mellitus were recruited to a low-intensity lifestyle intervention program by their general practitioners. Weight reduction ≥ 5% and improvement in exercise capacity of ≥ 10% from baseline to follow-up indicated a clinically significant lifestyle change. SOC was measured using the 13-item SOC questionnaire. RESULTS: The study involved 213 subjects with a mean body mass index of 37 (SD ± 6). Complete follow-up data were obtained for 131 (62%). Twenty-six participants had clinically significant lifestyle changes. There was a 21% increase in the odds of a clinically significant lifestyle change for each point increase in the baseline SOC score (odds ratio = 1.21; confidence interval = 1.11-1.32). The success rate was 14 times higher in the highest SOC score tertile group compared with the lowest. CONCLUSION: High SOC scores were good predictors of successful lifestyle change in subjects at risk of type 2 diabetes. SOC-13 can be used in daily practice to increase clinical awareness on the impact of mastery on the outcome of life-style intervention programs.


Subject(s)
Behavior Therapy , Diabetes Mellitus, Type 2/psychology , Diabetes Mellitus, Type 2/therapy , Life Style , Sense of Coherence , Adult , Exercise Tolerance , Female , Follow-Up Studies , Humans , Male , Middle Aged , Risk , Surveys and Questionnaires , Treatment Outcome , Weight Loss
5.
COPD ; 11(5): 531-8, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24831555

ABSTRACT

BACKGROUND: Knowledge about predictors for developing hypoxemia in the course of chronic obstructive pulmonary disease (COPD) progression is limited. The objective of the present study was to investigate predictors for overall PaO2, for a potential change in PaO2 over time, and for first occurrence of hypoxemia. METHODS: 419 patients aged 40-76 years with COPD GOLD stages II-IV underwent clinical and pulmonary function measurements, including repeated arterial blood gases over three years. Airway obstruction, lung hyperinflation, markers of systemic inflammation and cardiovascular health, exacerbation frequency, smoking habits, and body composition were tested as possible predictors of PaO2 and first episode of hypoxemia. RESULTS: In multivariate adjusted longitudinal analyses, forced expiratory volume in 1 second, total lung capacity and functional residual capacity (all in% predicted), resting heart rate and fat mass index were all associated with overall PaO2 (all P < 0.005). We found no change in PaO2 over time (ρ = 0.33), nor did we find evidence that any of the tested variables predicted change in PaO2 over time. In multivariate adjusted survival analyses, functional residual capacity and resting heart rate were predictors of episodic hypoxemia (both ρ < 0.005). CONCLUSIONS: This longitudinal study identified pulmonary, cardiac and metabolic risk factors for overall PaO2 and episodic hypoxemia, but detected no change in PaO2 over time.


Subject(s)
Hypoxia/blood , Oxygen/blood , Pulmonary Disease, Chronic Obstructive/blood , Respiratory Insufficiency/blood , Adult , Aged , Blood Gas Analysis , Cardiovascular Diseases/blood , Cardiovascular Diseases/complications , Disease Progression , Female , Forced Expiratory Volume , Functional Residual Capacity , Humans , Hypoxia/etiology , Inflammation/blood , Inflammation/complications , Longitudinal Studies , Male , Middle Aged , Multivariate Analysis , Partial Pressure , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/physiopathology , Respiratory Insufficiency/etiology , Risk Factors , Severity of Illness Index , Total Lung Capacity
6.
Eur J Clin Microbiol Infect Dis ; 33(3): 359-64, 2014 Mar.
Article in English | MEDLINE | ID: mdl-23999830

ABSTRACT

We tested the hypothesis that the results of real-time polymerase chain reaction (PCR) analyses for respiratory viruses would reduce antibiotic treatment and length of stay in elderly patients hospitalized with respiratory infections. Within 24 h of hospital admission, a total of 922 patients aged ≥60 years were interviewed for symptoms of ongoing respiratory tract infection. Symptomatic patients were swabbed for oropharyngeal/nasopharyngeal presence of viral pathogens immediately by members of the study group. During a 2-month period, non-symptomatic volunteers among interviewed patients were swabbed as well (controls). Oropharyngeal/nasopharyngeal swabs were analyzed with real-time PCR for nine common respiratory viruses. A total of 147 out of 173 symptomatic patients and 56 non-symptomatic patients (controls) agreed to participate in the study. The patients were allocated to three cohorts: (1) symptomatic and PCR-positive (S/PCR+), (2) symptomatic and PCR-negative (S/PCR-), or (3) non-symptomatic and PCR-negative (control). There were no non-symptomatic patients with a positive PCR result. A non-significant difference in the frequency of empiric antibiotic administration was found when comparing the S/PCR+ to the S/PCR- cohort; 16/19 (84 %) vs. 99/128 (77 %) (χ(2) = 0.49). Antibiotic treatment was withdrawn in only two patients in the S/PCR+ cohort after receiving a positive viral diagnosis. The length of stay did not significantly differ between the S/PCR+ and the S/PCR- groups. We conclude that, at least in our general hospital setting, access to early viral diagnosis by real-time PCR had little impact on the antimicrobial treatment or length of hospitalization of elderly patients.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/drug therapy , Aged , Aged, 80 and over , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Norway/epidemiology , Prospective Studies , Real-Time Polymerase Chain Reaction/methods , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Viruses/genetics , Viruses/isolation & purification
7.
Eur J Clin Microbiol Infect Dis ; 32(3): 381-5, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23052986

ABSTRACT

We tested the hypothesis that swabs from the nasopharynx carry a higher viral load than swabs from the oropharynx in patients with real-time polymerase chain reaction (PCR)-confirmed influenza infection. Using flocked swabs, oropharyngeal and nasopharyngeal samples were harvested from hospital-admitted influenza patients no later than 3 days after the initial detection of influenza virus. Comparison of cycle threshold (CT) values was performed to assess differences in viral load in the specimens. Seventeen patients were diagnosed with influenza B, 14 patients with influenza A(H1N1)pdm09, and one patient with influenza A(H3N2). Nasopharyngeal samples were positive at a lower CT value than the oropharyngeal samples [mean difference in CT 5.75, 95 % confidence interval (CI) 3.8-7.7, p < 0.01], suggesting that, on average, the calculated viral load of the nasopharyngeal samples was 54 times higher (95 % CI 13.7-210.8) than those of the oropharyngeal samples. The corresponding difference in the calculated viral load for influenza A(H1N1)pdm09 virus was 23 times (95 % CI 3.8-136.2, p < 0.01) and for influenza B virus, it was 80 times (95 % CI 9.3-694.6, p < 0.01). In patients with acute influenza, nasopharyngeal swabbing was clearly superior to oropharyngeal swabbing in terms of diagnostic yield by real-time PCR.


Subject(s)
Influenza, Human/virology , Nasopharynx/virology , Oropharynx/virology , Orthomyxoviridae/isolation & purification , Real-Time Polymerase Chain Reaction/methods , Viral Load , Adult , Aged , Female , Humans , Influenza, Human/diagnosis , Male , Middle Aged , Orthomyxoviridae/classification , Orthomyxoviridae/genetics
8.
BMJ Open ; 2(1): e000370, 2012.
Article in English | MEDLINE | ID: mdl-22267687

ABSTRACT

Background Fluticasone furoate/vilanterol (FF/VI) is a novel once-daily (OD) inhaled corticosteroid/long-acting ß(2) agonist combination in development for chronic obstructive pulmonary disease (COPD) and asthma. Trial design A multicentre, randomised, double-blind, parallel-group, placebo-controlled study. Methods Participants were patients with moderate-to-severe COPD treated with placebo or FF/VI 400/25 µg OD for 4 weeks. Study objectives were to assess the safety and efficacy of FF/VI 400/25 µg OD administered for 4 weeks via a novel dry powder inhaler. Co-primary end points were change from baseline in weighted mean (wm) heart rate 0-4 h postdose at day 28 and the incidence of adverse events (AEs). Secondary end points included change from baseline in trough forced expiratory volume in one second (FEV(1)) (23-24 h postdose; day 29) and wm FEV(1) (0-4 h postdose; day 28). Patients were randomised to receive FF/VI 400/25 µg or placebo in a 2:1 ratio; all patients and investigators were blinded to active or placebo treatment. Results 60 patients (mean age 64 years) were randomised (FF/VI: n=40; placebo: n=20), and all contributed data to the analysis. Mean screening post-bronchodilator FEV(1) per cent predicted was comparable between groups (FF/VI: 58.5%; placebo: 60.1%). The wm heart rate 0-4 h postdose was similar between groups (difference: 0.6 beats per minute; 95% CI -3.9 to 5.1). More on-treatment AEs were reported in the FF/VI group (68%) compared with the placebo group (50%). The most common drug-related AEs in the FF/VI group were oral candidiasis (8%) and dysphonia (5%). There were no clinically relevant effects on laboratory values, including glucose and potassium, or on vital signs or ECGs/Holters. The FF/VI group had statistically greater improvements compared with placebo in trough FEV(1) (mean difference 183 ml) and 0-4 h postdose wm FEV(1) (mean difference 236 ml). Conclusion FF/VI has a good safety and tolerability profile and improves lung function compared with placebo in patients with COPD. Trial registration number clinical trials.gov-NCT00731822.

9.
Hum Genet ; 131(7): 1105-14, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22200767

ABSTRACT

Two primary chitinases have been identified in humans--acid mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Mammalian chitinases have been observed to affect the host's immune response. The aim of this study was to test for association between genetic variation in the chitinases and phenotypes related to chronic obstructive pulmonary disease (COPD). Polymorphisms in the chitinase genes were selected based on previous associations with respiratory diseases. Polymorphisms that were associated with lung function level or rate of decline in the Lung Health Study (LHS) cohort were analyzed for association with COPD affection status in four other COPD case-control populations. Chitinase activity and protein levels were also related to genotypes. In the caucasian LHS population, the baseline forced expiratory volume in one second (FEV(1)) was significantly different between the AA and GG genotypic groups of the AMCase rs3818822 polymorphism. Subjects with the GG genotype had higher AMCase protein and chitinase activity compared with AA homozygotes. For CHIT1 rs2494303, a significant association was observed between rate of decline in FEV(1) and the different genotypes. In the African American LHS population, CHIT1 rs2494303 and AMCase G339T genotypes were associated with rate of decline in FEV(1). Although a significant effect of chitinase gene alleles was found on lung function level and decline in the LHS, we were unable to replicate the associations with COPD affection status in the other COPD study groups.


Subject(s)
Chitinases/genetics , Forced Expiratory Volume , Polymorphism, Single Nucleotide , Pulmonary Disease, Chronic Obstructive/genetics , Pulmonary Disease, Chronic Obstructive/physiopathology , Aged , Bronchoalveolar Lavage Fluid/chemistry , Case-Control Studies , Chitinases/metabolism , Female , Genetic Variation , Genotype , Humans , Lung/metabolism , Lung/physiopathology , Male , Middle Aged , Phenotype , Pulmonary Disease, Chronic Obstructive/enzymology , Respiratory Physiological Phenomena , Smoking
10.
Eur Respir J ; 38(6): 1261-77, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22130763

ABSTRACT

The prevalence of chronic obstructive pulmonary disease (COPD) has been extensively studied, especially in Western Europe and North America. Few of these data are directly comparable because of differences between the surveys regarding composition of study populations, diagnostic criteria of the disease and definitions of the risk factors. Few community studies have examined phenotypes of COPD and included other ways of characterising the disease beyond that of spirometry. The objective of the present Task Force report is to present recommendations for the performance of general population studies in COPD in order to facilitate comparable and valid estimates on COPD prevalence by various risk factors. Diagnostic criteria in epidemiological settings, and standardised methods to examine the disease and its potential risk factors are discussed. The paper also offers practical advice for planning and performing an epidemiological study on COPD. The main message of the paper is that thorough planning is worth half the study. It is crucial to stick to standardised methods and good quality control during sampling. We recommend collecting biological markers, depending on the specific objectives of the study. Finally, studies of COPD in the population at large should assess various phenotypes of the disease.


Subject(s)
Epidemiologic Studies , Pulmonary Disease, Chronic Obstructive/epidemiology , Research Design/standards , Biomarkers/analysis , Europe/epidemiology , Female , Humans , Male , North America/epidemiology , Prevalence , Pulmonary Disease, Chronic Obstructive/diagnosis , Risk Factors , Smoking/epidemiology
11.
Eur J Clin Microbiol Infect Dis ; 30(2): 159-65, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20853014

ABSTRACT

The purpose of this study was to compare the sampling efficacy of rayon swabs and nylon flocked swabs, and of oropharyngeal and nasopharyngeal specimens for the detection of respiratory viruses in elderly patients. Samples were obtained from patients 60 years of age or above who were newly admitted to Sorlandet Hospital Arendal, Norway. The patients were interviewed for current symptoms of a respiratory tract infection. Using rayon swabs and nylon flocked swabs, comparable sets of mucosal samples were harvested from the nasopharynx and the oropharynx. The samples were analysed using real-time polymerase chain reaction (PCR) methods. A total of 223 patients (mean age 74.9 years, standard deviation [SD] 9.0 years) were swabbed and a virus was recovered from 11% of the symptomatic patients. Regardless of the sampling site, a calculated 4.8 times higher viral load (95% confidence interval [CI] 1.3-17, p = 0.017) was obtained using the nylon flocked swabs as compared to the rayon swabs. Also, regardless of the type of swab, a calculated 19 times higher viral load was found in the samples from the nasopharynx as compared to the oropharynx (95% CI 5.4-67.4, p < 0.001). When swabbing for respiratory viruses in elderly patients, nasopharyngeal rather than oropharyngeal samples should be obtained. Nylon flocked swabs appear to be more efficient than rayon swabs.


Subject(s)
Respiratory Tract Infections/virology , Specimen Handling/methods , Virology/methods , Virus Diseases/diagnosis , Aged , Aged, 80 and over , Cellulose , Female , Humans , Male , Middle Aged , Mucous Membrane/virology , Nasopharynx/virology , Norway , Nylons , Oropharynx/virology , Polymerase Chain Reaction , Sensitivity and Specificity , Viral Load
12.
Eur Respir J ; 37(2): 255-63, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20562129

ABSTRACT

Lack of reproducibility of findings has been a criticism of genetic association studies on complex diseases, such as chronic obstructive pulmonary disease (COPD). We selected 257 polymorphisms of 16 genes with reported or potential relationships to COPD and genotyped these variants in a case-control study that included 953 COPD cases and 956 control subjects. We explored the association of these polymorphisms to three COPD phenotypes: a COPD binary phenotype and two quantitative traits (post-bronchodilator forced expiratory volume in 1 s (FEV1) % predicted and FEV1/forced vital capacity (FVC)). The polymorphisms significantly associated to these phenotypes in this first study were tested in a second, family-based study that included 635 pedigrees with 1,910 individuals. Significant associations to the binary COPD phenotype in both populations were seen for STAT1 (rs13010343) and NFKBIB/SIRT2 (rs2241704) (p<0.05). Single-nucleotide polymorphisms rs17467825 and rs1155563 of the GC gene were significantly associated with FEV1 % predicted and FEV1/FVC, respectively, in both populations (p<0.05). This study has replicated associations to COPD phenotypes in the STAT1, NFKBIB/SIRT2 and GC genes in two independent populations, the associations of the former two genes representing novel findings.


Subject(s)
Polymorphism, Genetic , Pulmonary Disease, Chronic Obstructive/genetics , STAT1 Transcription Factor/genetics , Sirtuin 2/genetics , Vitamin D-Binding Protein/genetics , Aged , Case-Control Studies , Female , Genetic Association Studies , Genetic Predisposition to Disease/epidemiology , Genetic Predisposition to Disease/genetics , Humans , Male , Middle Aged , Norway/epidemiology , Polymorphism, Single Nucleotide , Pulmonary Disease, Chronic Obstructive/epidemiology , Respiratory Function Tests/statistics & numerical data , Smoking/epidemiology
13.
Thorax ; 66(10): 903-9, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21163806

ABSTRACT

BACKGROUND: The identification of gene-by-environment interactions is important for understanding the genetic basis of chronic obstructive pulmonary disease (COPD). Many COPD genetic association analyses assume a linear relationship between pack-years of smoking exposure and forced expiratory volume in 1 s (FEV(1)); however, this assumption has not been evaluated empirically in cohorts with a wide spectrum of COPD severity. METHODS: The relationship between FEV(1) and pack-years of smoking exposure was examined in four large cohorts assembled for the purpose of identifying genetic associations with COPD. Using data from the Alpha-1 Antitrypsin Genetic Modifiers Study, the accuracy and power of two different approaches to model smoking were compared by performing a simulation study of a genetic variant with a range of gene-by-smoking interaction effects. RESULTS: Non-linear relationships between smoking and FEV(1) were identified in the four cohorts. It was found that, in most situations where the relationship between pack-years and FEV(1) is non-linear, a piecewise linear approach to model smoking and gene-by-smoking interactions is preferable to the commonly used total pack-years approach. The piecewise linear approach was applied to a genetic association analysis of the PI*Z allele in the Norway Case-Control cohort and a potential PI*Z-by-smoking interaction was identified (p=0.03 for FEV(1) analysis, p=0.01 for COPD susceptibility analysis). CONCLUSION: In study samples of subjects with a wide range of COPD severity, a non-linear relationship between pack-years of smoking and FEV(1) is likely. In this setting, approaches that account for this non-linearity can be more powerful and less biased than the more common approach of using total pack-years to model the smoking effect.


Subject(s)
DNA/genetics , Genome-Wide Association Study/methods , Polymorphism, Single Nucleotide , Pulmonary Disease, Chronic Obstructive/genetics , Smoking/genetics , alpha 1-Antitrypsin/genetics , Female , Follow-Up Studies , Forced Expiratory Volume , Genotype , Humans , Incidence , Male , Middle Aged , Norway/epidemiology , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/physiopathology , Respiratory Function Tests , Retrospective Studies , Risk Factors , Smoking/adverse effects , Smoking/metabolism , alpha 1-Antitrypsin/metabolism
14.
COPD ; 7(4): 262-8, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20673035

ABSTRACT

Superoxide dismutase-3 (SOD3) is a major extracellular antioxidant enzyme, and previous studies have indicated a possible role of this gene in chronic obstructive pulmonary disease (COPD). We hypothesized that polymorphisms in the SOD3 gene would be associated with COPD and COPD-related phenotypes. We genotyped three SOD3 polymorphisms (rs8192287 (E1), rs8192288 (I1), and rs1799895 (R213G)) in a case-control cohort, with severe COPD cases from the National Emphysema Treatment Trial (NETT, n = 389) and smoking controls from the Normative Aging Study (NAS, n = 472). We examined whether the single nucleotide polymorphisms (SNPs) were associated with COPD status, lung function variables, and quantitative computed tomography (CT) measurements of emphysema and airway wall thickness. Furthermore, we tried to replicate our initial findings in two family-based studies, the International COPD Genetics Network (ICGN, n = 3061) and the Boston Early-Onset COPD Study (EOCOPD, n = 949). In NETT COPD cases, the minor alleles of SNPs E1 and I1 were associated with a higher percentage of emphysema (%LAA950) on chest CT scan (p = .029 and p = .0058). The association with E1 was replicated in the ICGN family study, where the minor allele was associated with more emphysema (p = .048). Airway wall thickness was positively associated with the E1 SNP in ICGN; however, this finding was not confirmed in NETT. Quantitative CT data were not available in EOCOPD. The SNPs were not associated with lung function variables or COPD status in any of the populations. In conclusion, polymorphisms in the SOD3 gene were associated with CT emphysema but not COPD susceptibility, highlighting the importance of phenotype definition in COPD genetics studies.


Subject(s)
Polymorphism, Single Nucleotide , Pulmonary Disease, Chronic Obstructive/genetics , Pulmonary Emphysema/genetics , Superoxide Dismutase/genetics , Aged , Female , Gene Frequency , Genotype , Humans , Lung/diagnostic imaging , Male , Middle Aged , Phenotype , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/diagnostic imaging , Pulmonary Emphysema/complications , Smoking/genetics , Tomography, X-Ray Computed
15.
Eur J Neurol ; 17(11): 1352-7, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20443984

ABSTRACT

BACKGROUND AND PURPOSE: Invasive and non-invasive mechanical ventilation are therapeutic options in patients with amyotrophic lateral sclerosis (ALS). Related to known national ALS incidence figures, the study aims to examine gender aspects versus physiological data in patients with ALS commencing mechanical ventilation. METHODS: ata from two nationwide registers involving all patients with ALS in Norway and Sweden who started invasive and non-invasive mechanical ventilation during 2002-2007. RESULTS: The total ALS population on invasive and non-invasive mechanical ventilation comprised n = 308 subjects [Norway n = 96 (72% men), Sweden n = 212 (69% men)]. Compared to Swedish ALS incidence figures, our finding of a male/female ratio of 2.3/1 in patients with ALS on invasive and non-invasive mechanical ventilation shows a statistically significant male predominance in the use of mechanical ventilation (P-value 0.0084 Chi square). Only 6.7% of men and 3.8% of women had invasive (via tracheotomy) ventilation (P = 0.344). Initiation of mechanical ventilation was acute (not planned) in 18% of patients (no gender difference). Age distribution (mean age 62), pulmonary function tests (FVC%pred, FEV(1) %pred), daytime blood gas analyses (PaO(2), PaCO(2)) and survival revealed no statistically significant gender differences. CONCLUSION: In Norwegian and Swedish patients with ALS on invasive and non-invasive mechanical ventilation, two-thirds were men. Associated with known national ALS male/female incidence figures, our finding shows that statistically significantly more men than women with ALS are using mechanical ventilation. Physiological data and survival were equal in both genders. This may indicate the need for a more aggressive approach to stimulate mechanical ventilation in female patients with ALS.


Subject(s)
Amyotrophic Lateral Sclerosis/complications , Respiration, Artificial/methods , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Adult , Aged , Aged, 80 and over , Amyotrophic Lateral Sclerosis/mortality , Amyotrophic Lateral Sclerosis/therapy , Blood Gas Analysis/methods , Denmark , Disease Progression , Female , Forced Expiratory Volume/physiology , Humans , Male , Middle Aged , Norway , Predictive Value of Tests , Respiratory Function Tests/methods , Retrospective Studies , Sex Factors , Survival Analysis , Vital Capacity/physiology
16.
Eur Respir J ; 36(5): 1027-33, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20413541

ABSTRACT

Previous studies suggest a relationship between systemic inflammation and body composition in chronic obstructive pulmonary disease (COPD). We examined the relationships between body composition (fat free mass index (FFMI) kg·m(-2) and fat mass index (FMI) kg·m(-2)) and three plasma inflammatory markers C-reactive Protein (CRP), soluble tumour necrosis factor receptor 1 (sTNF-R1) and osteoprotegerin (OPG) in 409 stable COPD patients (aged 40-75 yrs, Global Initiative for Obstructive Chronic Lung Disease (GOLD) categories II-IV, 249 male) from the Bergen COPD Cohort Study in Norway. FFMI and FMI were measured by bioelectrical impedance. Plasma CRP (µg·mL(-1)), sTNF-R1 (pg·mL(-1)) and OPG (ng·mL(-1)) were determined by enzyme immunoassays. Correlations and Kruskal-Wallis tests were used for bivariate analyses. Linear regression models were fitted for each of the three markers, CRP, sTNF-R1 and OPG, with FFMI and FMI as explanatory variables including sex, age, smoking habits, GOLD category, hypoxaemia, Charlson Comorbidity Index and inhaled steroid use as potential confounders. CRP and sTNF-R1 levels correlated positively with both FFMI and FMI. The adjusted regression coefficients for an increase in logCRP per unit increase in FFMI was 1.23 (1.14-1.33) kg·m(-2) and 24.9 (11.8-38.1) kg·m(-2) for sTNF-R1. Higher FMI was associated with a lower OPG, with adjusted regression coefficient -0.14 (-0.23- -0.04), whereas FFMI was unrelated to OPG. In conclusion, COPD patients with low FFMI had lower not higher plasma levels of CRP and sTNF-R1, whereas higher fat mass was associated with higher CRP and sTNF-R1 and lower OPG.


Subject(s)
Biomarkers/blood , Body Composition/physiology , Cachexia/immunology , Cachexia/metabolism , Pulmonary Disease, Chronic Obstructive/immunology , Pulmonary Disease, Chronic Obstructive/metabolism , Adult , Aged , C-Reactive Protein/metabolism , Cross-Sectional Studies , Female , Humans , Inflammation/immunology , Inflammation/metabolism , Male , Middle Aged , Multivariate Analysis , Osteoprotegerin/blood , Receptors, Tumor Necrosis Factor, Type I/blood
17.
Eur Respir J ; 36(3): 517-23, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20185427

ABSTRACT

The aim of the present study was to assess whether asthma onset prior to entering the workforce influences whether a person holds a subsequent job with asthma-related inhalation exposures. The data of 19,784 adults from the European Community Respiratory Health Survey were analysed. For each respondent, a current or previously held job was linked to a job exposure matrix assigning high, low or no exposure to dust, gases or fumes. Jobs were also categorised according to the risk of exposures related to occupational asthma. Associations between asthma and subsequent occupational exposures were assessed using logistic regression models, with a random intercept for study centre and fixed adjustment for age, sex, type of study sample and smoking status. Of the respondents, 8% (n = 1,619) reported asthma with onset before completion of full-time education. This population was at decreased risk of having a job with high (odds ratio 0.79; 95% confidence interval 0.68-0.92) or low (0.91; 0.80-1.03) exposure to dust, gases or fumes. The associations were consistent across exposure types (dusts, gases or fumes) and for jobs with a high risk of occupational asthma. Adults with asthma onset prior to entering the workforce may be less likely to hold jobs involving inhalation exposures.


Subject(s)
Asthma/etiology , Asthma/genetics , Adult , Career Choice , Cross-Sectional Studies , Educational Status , Female , Health Status , Humans , Male , Occupational Exposure , Occupational Health , Odds Ratio , Regression Analysis , Surveys and Questionnaires
18.
Eur Respir J ; 36(3): 480-7, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20150201

ABSTRACT

The aim of our study was to examine sex-specific associations between different aspects of socioeconomic status (SES) (educational level, occupational status, income) and lung function in a general adult population. In the Hordaland County Cohort Study, 1,644 subjects aged 26-82 yrs at baseline answered questionnaires and performed post-bronchodilator spirometry both in 1996-1997 and in 2003-2006. We performed adjusted linear regression analysis on the effect of SES on decline in forced experimental volume in 1 s (FEV(1)), forced vital capacity (FVC) and FEV(1)/FVC. Mean annual decline in FEV(1) from baseline to follow-up was 57 mL (se 1.3) and 48 mL (se 1.0) for males and females, respectively. Males had a larger decline in FVC than females, while females had a larger decline in FEV(1)/FVC. Lower education and low occupational status were associated with larger male lung function decline. SES did not affect female lung function decline. However, marital status was a significant predictor; unmarried females had less decline than both married and widowed females in both FEV(1) (adjusted mean annual difference 8 mL and 16 mL) and FVC (adjusted mean annual difference 8 mL and 18 mL). Low SES was associated with increased lung function decline in males. For females, marital status was more important.


Subject(s)
Lung Diseases/physiopathology , Lung/physiopathology , Adult , Aged , Aged, 80 and over , Asthma/diagnosis , Asthma/physiopathology , Cohort Studies , Female , Humans , Lung Diseases/diagnosis , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Respiratory Function Tests , Risk Factors , Sex Factors , Socioeconomic Factors , Spirometry/methods
19.
Eur Respir J ; 35(3): 540-8, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19643942

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is considered an inflammatory pulmonary disorder with systemic inflammatory manifestations. The aim of this study was to assess the systemic levels of six inflammatory mediators in a large cohort of COPD patients and controls. 409 COPD patients and 231 healthy subjects, aged 40-75 yrs, were included from the first phase of the Bergen COPD Cohort Study. All COPD patients were clinically diagnosed by a physician, and had a forced expiratory volume in 1 s/forced vital capacity ratio less than 0.7 and a smoking history of >10 pack-yrs. The plasma levels of C-reactive protein (CRP), soluble tumour necrosis factor receptor (sTNFR)-1, osteoprotegrin, neutrophil activating peptide-2, CXCL16 and monocyte chemoattractant protein-4 were determined by ELISA. After adjustment for all known confounders, COPD patients had significantly lower levels of osteoprotegrin than subjects without COPD (p<0.05), and higher levels of CRP (p<0.01). Among COPD patients, CRP was elevated in patients with frequent exacerbations (p<0.05). sTNFR-1 and osteoprotegrin were both related to Global Initiative for Chronic Obstructive Lung Disease stage and frequency of exacerbations in the last 12 months (p<0.05). In addition, sTNFR-1 was significantly associated with important comorbidities such as hypertension and depression (p<0.05). The present study confirms that certain circulating inflammatory mediators are an important phenotypic feature of COPD.


Subject(s)
C-Reactive Protein/analysis , Osteoprotegerin/blood , Pulmonary Disease, Chronic Obstructive/blood , Receptors, Tumor Necrosis Factor, Type I/blood , Adult , Aged , Biomarkers/blood , Case-Control Studies , Chemokine CXCL16 , Chemokines, CXC/blood , Cohort Studies , Female , Humans , Inflammation/blood , Male , Middle Aged , Monocyte Chemoattractant Proteins/blood , Peptides/blood , Pulmonary Disease, Chronic Obstructive/immunology , Receptors, Scavenger/blood
20.
Clin Microbiol Infect ; 16(7): 909-11, 2010 Jul.
Article in English | MEDLINE | ID: mdl-19681958

ABSTRACT

To investigate the safety and practicability of conducting transthoracic fine-needle aspiration (TFNA) in a general hospital setting, we applied the TFNA procedure to 20 patients hospitalized with community-acquired pneumonia (CAP) within 36 h of admission. Also, a preliminary assessment was made of the potential value of adding TFNA to conventional methods of diagnostic microbiology. TFNA was easy to perform and caused little discomfort, and no serious adverse events were observed. In spite of ongoing antimicrobial treatment, a likely aetiological diagnosis was established for 14 of 20 (70%) of the patients. TFNA may provide important additional information on the aetiology of CAP.


Subject(s)
Biopsy, Fine-Needle , Community-Acquired Infections/diagnosis , Pneumonia, Bacterial/diagnosis , Adult , Aged , Aged, 80 and over , Biopsy, Fine-Needle/adverse effects , Biopsy, Fine-Needle/methods , Community-Acquired Infections/microbiology , Haemophilus influenzae/isolation & purification , Humans , Middle Aged , Moraxella catarrhalis/isolation & purification , Pilot Projects , Pneumonia, Bacterial/microbiology , Polymerase Chain Reaction , RNA, Ribosomal, 16S , Streptococcus pneumoniae/isolation & purification , Young Adult
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