Acute exacerbations of COPD and risk of lung cancer in COPD patients with and without a history of asthma.
ABSTRACT: Rationale:There is limited knowledge on the effect of acute exacerbations in chronic obstructive pulmonary disease (AECOPD) on lung cancer risk in COPD patients with and without a history of asthma. This study aims to examine whether AECOPD is associated with risk of lung cancer, and whether the effect depends on a history of asthma. Methods:In the GenKOLS study of 2003-2005, 852 subjects with COPD performed spirometry, and filled out questionnaires on smoking habits, symptoms and disease history. These data were linked to lung cancer data from the Cancer Registry of Norway through 2013. AECOPD, measured at baseline was the main predictor. To quantify differences in lung cancer risk, we performed Cox-proportional hazards regression. We adjusted for sex, age, smoking variables, body mass index, and lung function. Measurements and results:During follow-up, 8.8% of the subjects with, and 5.9% of the subjects without exacerbations were diagnosed with lung cancer. Cox regression showed a significant increased risk of lung cancer with one or more exacerbations in COPD patients without a history of asthma, HRR = 2.77 (95% CI 1.39-5.52). We found a significant interaction between a history of asthma and AECOPD on lung cancer. Conclusions:AECOPD is associated with an increased risk of lung cancer in COPD patients without a history of asthma.
Project description:Acute exacerbations of COPD involve increased symptoms such as cough, dyspnea and sputum production. These exacerbations are associated with increased mortality as well as decline in lung function. Non-invasive positive-pressure ventilation (NIPPV) is the preferred method of ventilatory support in respiratory failure secondary to AECOPD. NIPPV reduces work of breathing, improves oxygenation and ventilation and decreases both mortality and the risk of invasive ventilation. Other therapies for AECOPD include inhaled bronchodilators and systemic glucocorticoids. Antibiotics are recommended for severe exacerbations. Future areas of interest in treatment for AECOPD include utilization of biomarkers and extracorporeal carbon dioxide removal.
Project description:BACKGROUND:Lung cancer is a leading cause of death and hospitalization for patients with COPD. A detailed understanding of which clinical features of COPD increase risk is needed. METHODS:We performed a nested case-control study of Genetic Epidemiology of COPD (COPDGene) Study subjects with and without lung cancer, age 45 to 80 years, who smoked at least 10-pack years to identify clinical and imaging features of smokers, with and without COPD, that are associated with an increased risk of lung cancer. The baseline evaluation included spirometry, high-resolution chest CT scanning, and respiratory questionnaires. New lung cancer diagnoses were identified over 8 years of longitudinal follow-up. Cases of lung cancer were matched 1:4 with control subjects for age, race, sex, and smoking history. Multiple logistic regression analyses were used to determine features predictive of lung cancer. RESULTS:Features associated with a future risk of lung cancer included decreased FEV1/FVC (OR, 1.28 per 10% decrease [95% CI, 1.12-1.46]), visual severity of emphysema (OR, 2.31, none-trace vs mild-advanced [95% CI, 1.41-3.86]), and respiratory exacerbations prior to study entry (OR, 1.39 per increased events [0, 1, and ≥ 2] [95% CI, 1.04-1.85]). Respiratory exacerbations were also associated with small-cell lung cancer histology (OR, 3.57 [95% CI, 1.47-10]). CONCLUSIONS:The degree of COPD severity, including airflow obstruction, visual emphysema, and respiratory exacerbations, was independently predictive of lung cancer. These risk factors should be further studied as inclusion and exclusion criteria for the survival benefit of lung cancer screening. Studies are needed to determine if reduction in respiratory exacerbations among smokers can reduce the risk of lung cancer.
Project description:Background:A prolonged QT interval is associated with increased risk of Torsade de Pointes and cardiovascular death. The prevalence and clinical relevance of QT prolongation in acute exacerbations of COPD (AECOPD), with high risk for cardiac morbidity and mortality, is currently unclear. Methods:A dual cross-sectional study strategy was therefore designed. A retrospective study evaluated 140 patients with an AECOPD requiring hospitalization, half of which had prolonged QTc on the admission ECG. Univariate and multivariate analyses were conducted to determine associated factors; Kaplan-Meier and Cox regression analyses to assess prognostic significance. A prospective study evaluated 180 pulmonary patients with acute respiratory problems requiring hospitalization, to determine whether a prolonged QTc at admission represents an AECOPD-specific finding and to investigate the change in QTc-duration during hospitalization. Results:Retrospectively, hypokalemia, cardiac troponin T and conductance abnormalities on ECG were significantly and independently associated with QTc prolongation. A prolonged QTc was associated with increased all-cause mortality (HR 2.698 (95% CI 1.032-7.055), p=0.043), however, this association was no longer significant when corrected for age, FEV1 and cardiac troponin T. Prospectively, QTc prolongation was observed in 1/3 of the patients diagnosed with either an AECOPD, lung cancer, pulmonary infection or miscellaneous acute pulmonary disease, and was not more prevalent in AECOPD. The QTc-duration decreased significantly during hospitalization in patients with and without COPD. Conclusion:A prolonged QTc is a marker of underlying cardiovascular disease during an AECOPD. It is not COPD-specific, but a common finding during the acute phase of a pulmonary disease requiring urgent hospital admission.
Project description:<h4>Background</h4>Tracheal obstruction resulting from expiratory tracheal deformation has been associated with respiratory symptoms and severe airway exacerbations. In chronic obstructive pulmonary disease (COPD), acute exacerbations (AECOPD) create large intrathoracic pressure swings which may increase tracheal deformation. Excessive central airway collapse (ECAC) may be diagnosed when the tracheal area on expiration is less than 50% of that on inspiration. The prevalence of ECAC in AECOPD and its temporal course have not been systematically studied.<h4>Methods</h4>We prospectively recruited healthy volunteers (n = 53), stable outpatients with COPD (n = 40) and patients with hospitalised acute exacerbations of COPD (AECOPD, n = 64). 17 of the AECOPD group returned for repeat evaluation when clinically well at 6-12 weeks. All subjects underwent dynamic 320-slice computed tomography of the larynx and trachea during tidal breathing, enabling quantitation of tracheal area and dimensions (mean ± SD).<h4>Results</h4>No healthy individuals had ECAC. The prevalence of ECAC in stable COPD and AECOPD was 35% and 39% respectively. Mean tracheal collapse did not differ between stable COPD (57.5 ± 19.8%), AECOPD (53.8 ± 19.3%) and in the subset who returned when convalescent (54.9 ± 17.2%). AECOPD patients with and without ECAC had similar clinical characteristics.<h4>Conclusions</h4>Tracheal collapse in both stable and AECOPD is considerably more prevalent than in healthy individuals. ECAC warrants assessment as part of comprehensive COPD evaluation and management. Further studies should evaluate the aetiology of ECAC and whether it predisposes to exacerbations.
Project description:Individuals with chronic obstructive pulmonary disease (COPD) and asthma are an important but poorly characterised group. The genetic determinants of COPD and asthma overlap have not been studied. The aim of this study was to identify clinical features and genetic risk factors for COPD and asthma overlap. Subjects were current or former smoking non-Hispanic whites or African-Americans with COPD. Overlap subjects reported a history of physician-diagnosed asthma before the age of 40 years. We compared clinical and radiographic features between COPD and overlap subjects. We performed genome-wide association studies (GWAS) in the non-Hispanic whites and African-American populations, and combined these results in a meta-analysis. More females and African-Americans reported a history of asthma. Overlap subjects had more severe and more frequent respiratory exacerbations, less emphysema and greater airway wall thickness compared to subjects with COPD alone. The non-Hispanic white GWAS identified single nucleotide polymorphisms in the genes CSMD1 (rs11779254, p=1.57 × 10(-6)) and SOX5 (rs59569785, p=1.61 × 10(-6)) and the meta-analysis identified single nucleotide polymorphisms in the gene GPR65 (rs6574978, p=1.18 × 10(-7)) associated with COPD and asthma overlap. Overlap subjects have more exacerbations, less emphysema and more airway disease for any degree of lung function impairment compared to COPD alone. We identified novel genetic variants associated with this syndrome. COPD and asthma overlap is an important syndrome and may require distinct clinical management.
Project description:Low blood levels of 25-hydroxyvitamin D (25[OH]D) have been associated with a higher risk of respiratory infections in general populations and higher risk of exacerbations of lung disease in people with asthma. We hypothesized that low blood levels of 25(OH)D in patients with chronic obstructive pulmonary disease (COPD) would be associated with an increased risk of acute exacerbations of COPD (AECOPD).To determine if baseline 25(OH)D levels relate to subsequent AECOPD in a cohort of patients at high risk for AECOPD.Plasma 25(OH)D was measured at baseline in 973 participants on entry to a 1-year study designed to determine if daily azithromycin decreased the incidence of AECOPD. Relationships between baseline 25(OH)D and AECOPD over 1 year were analyzed with time to first AECOPD as the primary outcome and exacerbation rate as the secondary outcome.In this largely white (85%) sample of North American patients with severe COPD (mean FEV(1) 1.12L; 40% of predicted), mean 25(OH)D was 25.7 ± 12.8 ng/ml. A total of 33.1% of participants were vitamin D insufficient (?20 ng/ml but <30 ng/ml); 32% were vitamin D deficient (<20 ng/ml); and 8.4% had severe vitamin D deficiency (<10 ng/ml). Baseline 25(OH)D levels had no relationship to time to first AECOPD or AECOPD rates.In patients with severe COPD, baseline 25(OH)D levels are not predictive of subsequent AECOPD. Clinical trial registered with www.clinicaltrials.gov (NCT00119860).
Project description:BACKGROUND:Poorly controlled HIV infection is associated with increased risk for chronic obstructive pulmonary disease (COPD). Acute exacerbations of COPD (AECOPD) are major contributors to morbidity and mortality. Little is known about the association between HIV infection and AECOPD. METHODS:We identified 167 individuals with spirometry-confirmed COPD from a longitudinal study of current or former injection drug users at risk or with HIV infection. AECOPD, defined as self-report of worsening breathing requiring treatment with antibiotics or steroids, was assessed at 6-month study visits. Multivariable logistic regression identified factors associated with AECOPD. RESULTS:Of 167 participants, the mean age was 52 years; 89% were black, 30% female, and 32% HIV infected (median CD4 count: 312 cells per milliliter, 46% with detectable HIV RNA). After adjusting for age, gender, smoking history, comorbidity treatment, and airflow obstruction severity, HIV was independently associated with a 2.47 increased odds of AECOPD [95% confidence interval (CI): 1.22 to 5.00]. Compared with HIV-uninfected persons, HIV-infected persons with undetectable (<50 copies/mL) HIV RNA levels and those with a CD4 count ?350 cells per cubic millimeter demonstrated increased AECOPD (odds ratio, 2.91; 95% CI: 1.26 to 6.71; odds ratio, 4.16; 95% CI: 1.87 to 9.27, respectively). Higher AECOPD risk was observed with higher CD4 counts irrespective of treatment for comorbid diseases. CONCLUSIONS:HIV infection is independently associated with increased odds of AECOPD, potentially due to differences in treatment access and to variable disease manifestation by immune status. Providers should be aware that HIV infection may increase risk for AECOPD and that symptom may be more discernible with intact immune function.
Project description:BACKGROUND:Previous investigations in adult smokers from the COPDGene Study have shown that early-life respiratory disease is associated with reduced lung function, COPD, and airway thickening. Using 5-year follow-up data, we assessed disease progression in subjects who had experienced early-life respiratory disease. We hypothesized that there are alternative pathways to reaching reduced FEV1 and that subjects who had childhood pneumonia, childhood asthma, or asthma-COPD overlap (ACO) would have less lung function decline than subjects without these conditions. METHODS:Subjects returning for 5-year follow-up were assessed. Childhood pneumonia was defined by self-reported pneumonia at < 16 years. Childhood asthma was defined as self-reported asthma diagnosed by a health professional at < 16 years. ACO was defined as subjects with COPD who self-reported asthma diagnosed by a health-professional at ? 40 years. Smokers with and those without these early-life respiratory diseases were compared on measures of disease progression. RESULTS:Follow-up data from 4,915 subjects were examined, including 407 subjects who had childhood pneumonia, 323 subjects who had childhood asthma, and 242 subjects with ACO. History of childhood asthma or ACO was associated with an increased exacerbation frequency (childhood asthma, P < .001; ACO, P = .006) and odds of severe exacerbations (childhood asthma, OR, 1.41; ACO, OR, 1.42). History of childhood pneumonia was associated with increased exacerbations in subjects with COPD (absolute difference [?], 0.17; P = .04). None of these early-life respiratory diseases were associated with an increased rate of lung function decline or progression on CT scans. CONCLUSIONS:Subjects who had early-life asthma are at increased risk of developing COPD and of having more active disease with more frequent and severe respiratory exacerbations without an increased rate of lung function decline over a 5-year period. TRIAL REGISTRY:ClinicalTrials.gov; No. NCT00608764; https://clinicaltrials.gov.
Project description:Bilirubin is a potent anti-oxidant and higher serum concentrations of bilirubin have been associated with better lung function, slower lung function decline, and lower incidence of chronic obstructive pulmonary disease (COPD). We sought to determine whether elevated bilirubin blood concentrations are associated with lower risk for acute exacerbations of COPD (AECOPD).We performed a secondary analyses of data in the Simvastatin for Prevention of Exacerbations in Moderate-to-Severe COPD (STATCOPE) and the Azithromycin for Prevention of Exacerbations of COPD (MACRO) studies. We used time-dependent multivariable Cox proportional hazards analyses, using bilirubin concentrations prior to first AECOPD as the exposure variable and time to first AECOPD as the outcome variable. STATCOPE was used for model development, with validation in MACRO.In STATCOPE (n = 853), higher bilirubin was associated with a lower but statistically insignificant hazard for AECOPD, (adjusted hazard ratio [aHR] 0.89 per log10 increase [95%CI: 0.74 to 1.09; p = 0.26]). In the validation MACRO study (n = 1018), higher bilirubin was associated with a significantly lower hazard for AECOPD (aHR 0.80 per log10 increase [95%CI: 0.67 to 0.94; p = 0.008]).Bilirubin may be a biomarker of AECOPD risk and may be a novel therapeutic target to reduce AECOPD risk.ClinicalTrials.gov NCT01061671 (registered 02 February 2010) and ClinicalTrials.gov NCT00325897 (registered 12 May 2006).
Project description:<h4>Background</h4>In primary care there is uncertainty about which patients with acute exacerbations of COPD (AECOPD) benefit from antibiotics.<h4>Objectives</h4>To identify which types of COPD patients get the most antibiotics in primary care to support targeted antibiotic stewardship.<h4>Methods</h4>Observational study of COPD patients using a large English primary care database with 12?month follow-up. We estimated the incidence of and risk factors for antibiotic prescribing relative to the number of AECOPD during follow-up, considering COPD severity, smoking, obesity and comorbidity.<h4>Results</h4>From 157 practices, 19594 patients were diagnosed with COPD, representing 2.6% of patients and 11.5% of all prescribed antibiotics. Eight hundred and thirty-three (4.5%) patients with severe COPD and frequent AECOPD were prescribed six to nine prescriptions per year and accounted for 13.0% of antibiotics. Individuals with mild to moderate COPD and zero or one AECOPD received one to three prescriptions per year but accounted for 42.5% of all prescriptions. In addition to COPD severity, asthma, chronic heart disease, diabetes, heart failure and influenza vaccination were independently associated with increased antibiotic use.<h4>Conclusions</h4>Patients with severe COPD have the highest rates of antibiotic prescribing but most antibiotics are prescribed for patients with mild to moderate COPD. Antibiotic stewardship should focus on the dual goals of safely reducing the volume of prescribing in patients with mild to moderate COPD, and optimizing prescribing in patients with severe disease who are at significant risk of drug resistance.