Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Exacerbations”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources
PubMed1990

Acute exacerbations in Chinese patients with chronic hepatitis B virus (HBV) infection. Incidence, predisposing factors and etiology.

Three hundred and eighty-six Chinese patients (262 men and 124 women), age 5-74 years, with chronic hepatitis B virus (HBV) infection were prospectively followed for 1-5 years to determine the incidence, predisposing factors and etiology of acute exacerbations that occurred during the course of chronic HBV infection. Group I consisted of 334 patients with serum alanine aminotransferase (ALT) levels below 200 IU/l at presentation. Of these, 29 (8.7%) patients developed 32 episodes of acute exacerbation during follow-up. The cumulative probabilities of developing exacerbations were 6.3% and 15% at the end of 1 and 4 years, respectively. Group II included 52 patients with ALT levels above 200 IU/l at presentation. Of these, 19 (37%) patients developed 26 episodes of exacerbation during follow-up. The cumulative probabilities of developing eacerbations were 24% and 47% at the end of 1 and 4 years, respectively. In both groups, the probability of developing exacerbations was slightly higher in men and significantly higher in those above the age of 20 and those who were HBeAg positive. Logistic regression analysis showed that HBeAg positivity (p less than 0.00001), elevated ALT levels (greater than 200 IU/l) at presentation (p less than 0.0001) and male sex (p = 0.03) were associated with a significantly higher probability of developing exacerbations. Twenty eight (48%) episodes of exacerbation were accompanied by symptoms of acute hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2006

Patient's perception of exacerbations of COPD--the PERCEIVE study.

The evaluation of therapies requires the development of patient-reported outcomes (PROs) that help clinicians to understanding the symptoms, perceptions and feelings of patients with exacerbations of chronic obstructive pulmonary disease (COPD). With the aim of obtaining information on the perceptions of patients with COPD, their exacerbations and expectations of treatment, a random telephone contact survey in six countries was performed. From 83,592 households screened, 1100 subjects with symptoms compatible with COPD were identified. The most frequent symptom was shortness of breath (78%). The most frequent complaint was that due to their COPD: "they could not complete the activities they like to do" (54%); 17% (187) of individuals were afraid that their COPD would cripple, or eventually kill them. Exacerbations generated a mean of 5.1 medical visits/year (SD=4.6) with the mean duration of exacerbation symptoms being 10.5 days. Increased coughing was the exacerbation symptom having the strongest impact on well-being (42%). Fifty-five percent of patients declared that quicker symptom relief was the most desired requirement for treatment. New data are provided on the impact of COPD and its exacerbations on the daily life of patients. These data will help to develop PROs designed to evaluate the effectiveness of different therapies for exacerbated COPD.

Activities of Daily Living↗
PubMed2006

Relationship between airway colonization, inflammation and exacerbation frequency in COPD.

RATIONALE: To evaluate bacterial colonization and the airway inflammatory response, and its relationship to the frequency of exacerbation in patients with stable chronic obstructive pulmonary disease (COPD). METHODS: Quantitative bacteriologic cultures, neutrophil elastase, myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-8 were measured in bronchoalveoler lavage (BAL) in 39 patients with stable COPD [19 with frequent exacerbation (> or = 3/year), and 20 with infrequent] and in 18 healthy controls (10 smokers and 8 non-smokers). RESULTS: BAL revealed the microorganisms with potential pathogenicity above the established threshold (> or = 10(3)cfu/ml) in 68.4% of patients with frequent exacerbation, 55% of infrequent exacerbation, 40% of smokers and 12.5% of non-smokers controls (P=0.05). BAL MPO, IL-8 and TNF-alpha levels were found to be significantly higher in COPD as compared to controls (P=0.001). However, only IL-8 level was significantly higher in COPD patients with frequent exacerbation as compared to infrequent (P=0.001). Airway bacterial load correlated with levels of airway inflammation markers in COPD (P<0.05). CONCLUSION: The bacterial load and airway inflammation contributes to each other in stable COPD. However, there is a link only between interleukine (IL)-8 and frequent exacerbations. Clearly, the relationship between bacterial colonization, airway inflammation and frequent exacerbations is of major importance in understanding of the COPD pathogenesis.

Biomarkers↗
PubMed1986

Role of respiratory viruses in exacerbations of primary nephrotic syndrome.

To determine whether respiratory virus infections (URI) are associated with exacerbation of nephrotic syndrome (NS) in childhood, a prospective two-winter study of 32 children with NS was done. We obtained pre- and post-season viral serologic studies, biweekly nose and throat viral cultures, daily urinalysis, biweekly telephone follow-up for URI and renal complaints, and clinical assessments as indicated. When a URI occurred, viral cultures were done weekly if the child was at home and twice weekly if hospitalized. Sixty-one URIs occurred; the agent was identified in 33 (51.6%) (respiratory syncytial virus 14, influenza virus five, parainfluenza virus five, varicella zoster virus four, adenovirus three, Mycoplasma pneumoniae one, and Chlamydia trachomatis one). Forty-one exacerbations occurred, 71% with URI; 29% had no URI during the preceding 10 days (P less than 0.01). Total relapse occurred in 29 of 41 exacerbations, 69% with URI and 31% without URI (P less than 0.01). Patients with unstable NS had more exacerbations than those with stable NS (15 of 19 (79%) vs four of 13 (31%), P less than 0.001) and more URI (2.32 vs 1.46 per child, P less than 0.05). Exacerbations in patients with minimal change, mesangioproliferative, and focal glomerulosclerosis occurred in 40%, 60%, and 64%, respectively. We conclude that exacerbations and relapses of childhood NS are temporally related to URI. Inasmuch as multiple viral agents were associated with exacerbations, nonspecific host response to infection, not viral antigen or antibody response, may be the link to NS.

Adolescent↗
PubMed2003

[Results of a preventive program and assisted hospital discharge for COPD exacerbation. A feasibility study].

BACKGROUND AND OBJECTIVE: Exacerbation of chronic obstructive pulmonary disease (COPD) is one of the most frequent causes of hospital admission. We examined the results and feasibility of two programs conducted by a hospital respiratory unit aimed to reduce both the length of hospital stay and the number of hospital admissions for COPD acute exacerbation. PATIENTS AND METHOD: a) Assisted hospital discharge program: Patients admitted for acute exacerbation who met our criteria for early discharge were sent home with the support of a respiratory nurse. Home visits were carried out and direct phone contact with the nurse and physician was provided during a limited period of 6 weeks. Outcome variables studied were length of hospital admission and need for hospital reentry. b) Exacerbation prevention program: A group of patients with severe COPD and at least 3 hospital admissions for exacerbation during the previous year were included. These patients underwent an educational program and were given unlimited direct phone access to the respiratory nurse and physician. When necessary, home visits were carried out. The main outcome variable of this program was the number of hospital admissions. RESULTS: a) Assisted hospital discharge program: A total of 97 patients were included. The mean length of hospital stay was 5.4 1.7 days, which was significantly shorter than the previous average length of stay in our respiratory unit for a diagnosis of COPD exacerbation (8.52 days). The rate of hospital reentry was 17% (within the first 3 months). b) Exacerbation prevention program: 23 patients were enrolled. In this group, the number of hospital admissions decreased significantly from 5.0 1.8 to 1.7 2.4 per year (p = 0.001). Visits to the emergency department were also decreased, from 1.2 1.6 to 0.4 1.6 per patient (p = 0.05). Finally, the length of hospital stay decreased from 38 17 to 16 20 days (p = 0.0001). CONCLUSIONS: A combined use of hospital resources and home care programs which are specifically addressed to severe COPD patients can reduce the need for hospital admission.

Aged↗
PubMed2002

[The epidemiology of COPD and asthma exacerbations in a general hospital].

This retrospective study identified the clinical and epidemiological characteristics of patients coming to the emergency room of our hospital with exacerbated asthma or chronic obstructive pulmonary disease (COPD) in 1993 and 1994. We followed a previously established protocol to review the case histories of patients from both years. The 1,592 exacerbations we identified in 1,209 asthmatics accounted for 0.9% of all emergency visits, with a mean of 2.2 1.6 (0-9) visits daily. The 2,106 exacerbations of COPD in 1,208 patients accounted for 1.2% of all emergencies, with a mean 2.9 (1-12) visits per day. The mean age was 51.2 (14-93) years for asthmatics and 70.3 (29-96) years for COPD patients. Of asthmatics, 69.8% were women and 30.1% were men, whereas 91.4% of COPD patients were men. The readmission rate was 3.4% for asthmatics and 4.8% for COPD patients. The hospitalization rate was 26.7% for asthmatics and 49.4% for COPD exacerbation patients. The hospital saw 22.6% of asthma exacerbations between midnight and 8 a.m. and 41.6% of COPD exacerbations during the same time frame. For both diseases, more emergencies occurred in winter. Correlation between asthma and COPD and declared influenza cases in the community were r = 0.63 (p < 0.001) for asthma and r = 0.83 (p < 0.0001) for COPD. Our findings underline the considerable emergency care burden generated by exacerbations of obstructive airway diseases and suggest that community acquired respiratory infections are usually the underlying cause.

Adolescent↗
PubMed2004

[The COPD-PE study: prevalence and prediction of pulmonary embolism in acute exacerbations of chronic obstructive pulmonary disease].

INTRODUCTION: Patients suffering from chronic obstructive pulmonary disease (COPD) are often admitted to hospital with an exacerbation of their disease that manifests itself with an increase in cough and/or sputum, increased dyspnoea and sometimes chest pain. These episodes are most often attributed to an acute exacerbation of bronchial infection but the real cause is often unknown. COPD is considered a risk factor for pulmonary embolism (PE) and PE is part of the differential diagnosis of an acute exacerbation of COPD. However, the symptoms of these two conditions overlap to a considerable extent and the investigation of PE is often ignored in these patients. Therefore the true prevalence of PE in this situation is unknown. Nevertheless several small series suggest that up to 30% of patients seen as emergencies with exacerbations of COPD may have a deep vein thrombosis or PE. The aims of this study are therefore: 1. To evaluate the prevalence of PE in patients admitted as emergencies with exacerbations of COPD; and 2. To attempt to develop a prediction guide for PE in this population in order to identify the patients in whom PE should be investigated. MATERIALS AND METHODS: 600 consecutive patients admitted as emergencies with exacerbations of COPD will be included in a cross sectional study in three university hospitals (Geneva and Lausanne in Switzerland, and Amiens in France). Patients fulfilling the inclusion criteria will be investigated by a diagnostic algorithm appropriate for the study of PE, including D-dimer levels and, in those with abnormal results, ultrasonic scan of the deep veins of the legs and spiral CT scan. The patient characteristics on admission will be incorporated in a multivariate regression analysis in an attempt to identify the predictive factors for PE in these patients. The expected duration of the study is 24 months. EXPECTED RESULTS: This study should determine the prevalence of PE in patients admitted as emergencies with exacerbations of COPD and therefore help decide when, and in which patients, a systematic search for PE should be undertaken.

Algorithms↗
PubMed2002

Prediction of macular edema exacerbation after phacoemulsification in patients with nonproliferative diabetic retinopathy.

PURPOSE: To ascertain whether the aqueous humor levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and protein can predict the postoperative exacerbation of macular edema in patients with nonproliferative diabetic retinopathy (NPDR) after phacoemulsification surgery for cataract. SETTING: Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University, Tokyo, Japan. METHODS: This prospective study included 104 consecutive patients (104 eyes) with NPDR who had cataract surgery. The concentrations of VEGF and IL-6 in aqueous humor specimens obtained during cataract surgery were measured by enzyme-linked immunosorbent assay. Patients were followed for 6 months to assess the postoperative exacerbation of macular edema. RESULTS: Ninety patients (87%) achieved a visual acuity of 20/40 or better. Exacerbation of macular edema was seen in 30 eyes (29%) after 6 months. Hypertension and the aqueous levels of VEGF, IL-6, and protein were significantly correlated with the exacerbation of macular edema (odds ratio 1.16, 1.33, 1.27, and 1.28, respectively). In contrast, there was no correlation between the exacerbation of macular edema and other systemic factors. Multivariate logistic regression analysis showed that the aqueous VEGF level increase of 100 pg/mL increased the macular edema after phacoemulsification surgery (odds ratio 1.53). CONCLUSIONS: A high VEGF level in the aqueous humor predicted a significant risk for the postoperative exacerbation of macular edema. A model was developed to predict the risk exacerbation.

Aged↗
PubMed2002

Management of asthma exacerbations.

The 1997 Expert Panel Report 2 from the National Asthma Education and Prevention Program* details principles and goals for managing asthma exacerbations, based on scientific literature and the opinion of the panel. The panel's recommendations are summarized here, along with approaches to the evaluation and management of patients with asthma exacerbations. Methods to assess and classify the severity of asthma exacerbations are discussed, and treatment objectives for mild, moderate, and severe exacerbations are presented, along with a discussion of postinfectious acute airway hyperresponsiveness. A review of pharmacologic agents used in the treatment of asthma exacerbations is also included. Key points in the management of asthma exacerbations include the notion that early treatment is the best strategy for management. Important elements of early treatment include recognition of early signs of worsening asthma, a written action plan to guide patient self-management, appropriate intensification of therapy, and prompt communication between patient and provider about deterioration in asthma control. Other key points include the use of inhaled beta 2-adrenergic agonists to provide prompt relief of airflow obstruction, the early use of systemic corticosteroids for patients with moderate to severe exacerbations or for patients who fail to respond promptly and completely to an inhaled beta 2-adrenergic agonist, and monitoring response to therapy with serial measurements of lung function.

Administration, Inhalation↗
PubMedDate not supplied

Management of asthma exacerbations.

The 1997 Expert Panel Report 2 from the National Asthma Education and Prevention Program details principles and goals for managing asthma exacerbations, based on scientific literature and the opinion of the panel. The panel's recommendations are summarized here, along with approaches to the evaluation and management of patients with asthma exacerbations. Methods to assess and classify the severity of asthma exacerbations are discussed, and treatment objectives for mild, moderate, and severe exacerbations are presented, along with a discussion of postinfectious acute airway hyperresponsiveness. A review of pharmacologic agents used in the treatment of asthma exacerbations is also included. Key points in the management of asthma exacerbations include the notion that early treatment is the best strategy for management. Important elements of early treatment include recognition of early signs of worsening asthma, a written action plan to guide patient self-management, appropriate intensification of therapy, and prompt communication between patient and provider about deterioration in asthma control. Other key points include the use of inhaled beta 2-adrenergic agonists to provide prompt relief of airflow obstruction, the early use of systemic corticosteroids for patients with moderate to severe exacerbations or for patients who fail to respond promptly and completely to an inhaled beta 2-adrenergic agonist, and monitoring response to therapy with serial measurements of lung function.

Anti-Asthmatic Agents↗
PubMed2002

Risk factors for symptom exacerbation among treated patients with substance use disorders.

AIMS: The purpose of this study was to develop an index of risk factors to identify patients prospectively with substance use disorders whose substance use symptoms exacerbate during or shortly after treatment, and to identify characteristics of care that may reduce the likelihood of exacerbation. DESIGN, SETTING, PARTICIPANTS: On the basis of data obtained from a nation-wide outcomes monitoring system, a group of 2809 treated patients experienced an exacerbation of their substance use symptoms. These patients were matched on baseline substance abuse problems with 5618 patients who remained stable or improved. MEASUREMENTS AND FINDINGS: Risk factors for substance use symptom exacerbation included younger age, non-married status and residential instability; long-term use of drugs, prior arrests, prior alcohol treatment, alcohol and drug abuse or dependence diagnoses, cocaine abuse or dependence and more severe self-rated drug problems; and psychiatric problems. High-risk patients who obtained a longer episode of mental health care were less likely to experience an exacerbation of symptoms. CONCLUSIONS: Clinicians can identify at treatment entry patients whose substance use symptoms are likely to exacerbate and, by providing these patients a longer duration of care, may reduce the likelihood of symptom exacerbation.

Adolescent↗
PubMed2003

A prospective study characterizing full-length hepatitis B virus genomes during acute exacerbation.

BACKGROUND & AIMS: Hepatitis B virus (HBV) evolves rapidly in patients with chronic hepatitis B, and HBV variation may trigger acute exacerbation. To study this relationship, we investigated full-length viral sequences before, during, and after exacerbation. METHODS: We prospectively studied 14 patients with exacerbation of hepatitis B, either spontaneously (n = 4) or after receiving various medical interventions (n = 10), and measured their serum alanine aminotransferase (ALT) and HBV DNA levels monthly. Full-length HBV genomes at baseline, at the peak of serum viral load, at ALT peak, and after ALT peak were obtained by polymerase chain reaction, sequenced, and compared. Replication activities of serial HBV variants were assayed by in vitro transfection. RESULTS: Serum viral load was increased in all exacerbations. Viral peak preceded ALT peak in 13 (93%) of the 14 patients. At virologic peak, 12 patients (86%) harbored viral genome identical to the corresponding baseline genome. At and after ALT peak, 9 (64%) and 7 (50%) of the viral genomes remained identical to baseline, respectively. Mean nucleotide change per genome was 0.2 at virologic peak but increased to 4.4 and 8.1 at and after ALT peak, respectively. The replication potential of the viral variant that emerged during or after exacerbation was equivalent to that at baseline. CONCLUSIONS: Most exacerbations were preceded by an upsurge of serum HBV identical to the preexisting HBV strain. After exacerbation, about half of the patients were repopulated by a different viral variant, which was likely a result of immune selection.

Adult↗
PubMed2002

Preemptive use of lamivudine reduces hepatitis B exacerbation after allogeneic hematopoietic cell transplantation.

Exacerbation of hepatitis B virus (HBV) is a serious cause of morbidity and mortality in hepatitis B surface antigen (HBsAg)-positive patients undergoing transplantation. Our aim was to evaluate the effectiveness of lamivudine to prevent hepatitis due to exacerbation of HBV in HBsAg-positive patients treated with allogeneic hematopoietic cell transplantation. We studied 20 consecutive HBsAg-positive recipients of allogeneic hematopoietic cell transplantation who received lamivudine 100 mg daily starting one week before transplantation until week 52 after transplantation (group 1). Serial serum alanine aminotransferase and HBV DNA levels were measured before and after transplantation at 4- to 8-week intervals for the first year and then 4- to 12-week intervals. Their virologic and clinical outcomes were compared with 20 case-matched recipients who did not receive any antiviral therapy to HBV (anti-HBV) before and after hematopoietic cell transplantation (group 2). After transplantation, 9 patients (45%) in group 2 and one patient (5%) in group 1 had hepatitis due to exacerbation of HBV (P <.008), with 3 hepatic failures in group 2 and none in group 1. The one-year actuarial probability of survival without hepatitis due to exacerbation of HBV was higher in group 1 than group 2 (94.1% vs. 54.3%, P =.002). By multivariate Cox analysis, preemptive use of lamivudine effectively reduced hepatitis due to exacerbation of HBV (adjusted hazards ratio, 0.09; P =.021). In conclusion, preemptive lamivudine reduced HBV exacerbation. The use of lamivudine with other immunosuppressive regimens to prevent exacerbation of HBV should be further explored.

Adolescent↗
PubMed2002

Urinary desmosine excretion in acute exacerbations of COPD: a preliminary report.

Desmosine (DES) is an elastin-derived, cross-link amino acid, which is not metabolized; hence, its urinary levels reflect elastin breakdown. We hypothesized that elastin degradation should increase as a result of increased lung inflammation during an acute exacerbation of COPD and should decrease after recovery. To test this hypothesis we measured DES in three urine samples from nine COPD subjects during the first 5 days of an acute exacerbation and at 2 months after recovery. We also measured forced expiratory volume in 1 sec (FEV1) to monitor the effects ofthe exacerbation on ventilatory function. The mean (SD) FEV1 was 45 (15)% predicted during the exacerbation and 57.8 (16)% predicted 2 months later (P=0.00001). The mean (SD) DES excretion was 25.3 (9) microg g(-1) creatinine at day 1;23.5 (9) at day 3 and 24 (9) at day 5 of the exacerbation. The mean (SD) urinary DES excretion 60 days after discharge was 20.9 (7) microg g(-1) creatinine (P=0.049) in comparison with the mean of the three acute-phase values. The size of the increase in desmosine excretion during exacerbation is small, 3.2 microg g(-1) creatinine or 16% of the recovery desmosine value. We conclude that there is a small but statistically significant increase in lung elastin breakdown in the body during an acute exacerbation of COPD.

Acute Disease↗
PubMed2005

Pathogenesis and treatment of acute exacerbations of chronic obstructive pulmonary disease.

Once thought to be a mere nuisance, exacerbations are now recognized as a major contributor to the morbidity and mortality associated with chronic obstructive pulmonary disease. This recognition has led to research using new investigative tools that has substantially enhanced our understanding of the pathogenesis of exacerbations. Several overlapping etiologies can precipitate the symptom complex of an exacerbation. Treatment of exacerbations requires the use of several therapeutic modalities with the goal of restoring the patient to baseline. Results of recent clinical trials and observational studies have allowed a refinement of the approach to treatment of exacerbations. These include a rational, stratified approach to the use of antibiotics and several trials substantiating the use of systemic corticosteroids. Relapse or failure rates of 20 to 33% have been described in the treatment of acute exacerbation, with these treatment failures contributing substantially to the costs associated with exacerbations. Improved treatment based on enhanced understanding and good clinical evidence should lead to better outcomes in this common clinical entity.

Acute Disease↗
PubMed2001

Does influenza vaccination prevent asthma exacerbations in children?

OBJECTIVE: Influenza can exacerbate asthma, particularly in children. The effectiveness of influenza vaccine in preventing influenza-related asthma exacerbations, however, is not known. We evaluated influenza vaccine effectiveness in protecting children against influenza-related asthma exacerbations. STUDY DESIGN: We conducted a population-based retrospective cohort study with medical and vaccination records in 4 large health maintenance organizations in the United States during the 1993-1994, 1994-1995, and 1995-1996 influenza seasons. We studied children with asthma who were 1 through 6 years of age and who were identified by search of computerized databases of medical encounters and pharmacy dispensings. Main outcome measures were exacerbations of asthma evaluated in the emergency department or hospital. RESULTS: Unadjusted rates of asthma exacerbations were higher after influenza vaccination than before vaccination. After adjustment was done for asthma severity by means of a self-control method, however, the incidence rate ratios of asthma exacerbations after vaccination were 0.78 (95% CI: 0.55 to 1.10), 0.59 (0.43 to 0.81), and 0.65 (0.52 to 0.80) compared with the period before vaccination during the 3 influenza seasons. CONCLUSIONS: After controlling for asthma severity, we found that influenza vaccination protects against acute asthma exacerbations in children.

Acute Disease↗
PubMed2006

Pathogenesis of bacterial exacerbations of COPD.

Acute exacerbations are significant events in the course of COPD. The pathogenesis of exacerbations was poorly understood, specifically, the role of bacteria was highly controversial. Recent observations have demonstrated that bacterial infection is involved in about half of the exacerbations. The predominant mechanism of bacterial exacerbation in COPD appears to be acquisition of new strains of bacterial pathogens from the environment that are able to establish infection in the tracheobronchial tree in COPD because of compromised innate lung defenses. These pathogens interact with airway cells, elicit an inflammatory response, which underlies the pathophysiology and symptoms characteristic of exacerbation. An immune response that can be mucosal, systemic or both develops to the infecting bacterial strain. This immune response contains the infectious process, could eradicate the infecting pathogen and prevent re-infection with the same strain. However, because of antigenic diversity among bacterial strains, this immunity tends to be strain-specific rather than widely protective. Other mechanisms, including increase in bacterial load and interaction with other etiologies such as viruses, also could contribute to bacterial exacerbations. Improved understanding of the host-pathogen interaction in the airways in COPD will lead to novel approaches to prevention and treatment of exacerbations.

Acute Disease↗
PubMed2026

Systemic Platelet Activation and Respiratory Exacerbations, Pulmonary Symptoms, and Mortality among Current and Former Smokers in SPIROMICS.

RATIONALE: Platelet activation is elevated in chronic obstructive pulmonary disease (COPD) and associated with self-reported respiratory symptoms. Observational studies link the antiplatelet drug aspirin to lower exacerbation rates and fewer symptoms. However, it is unknown if platelet activation predicts incident respiratory exacerbations or mortality. OBJECTIVE: Is systemic platelet activation prospectively associated with respiratory exacerbations and mortality among ever-smokers with or at risk for COPD? METHODS: We measured two systemic platelet activation biomarkers, urinary 11-dehydro-thromboxane B2 (11dTxB2) and plasma soluble CD40 ligand (sCD40L), at baseline in self-reported aspirin non-users in the longitudinal SPIROMICS cohort. Adjusted generalized negative binomial and linear mixed-effects models assessed associations between these biomarkers and prospective rates of total and severe exacerbations, plus cross-sectional and longitudinal respiratory health (St. George's Respiratory Questionnaire, COPD Assessment Test, modified Medical Research Council questionnaire, and six minute walk distance). Cox proportional hazard and competing risk models evaluated associations between platelet activation biomarkers and all-cause and cause-specific mortality. RESULTS: Among 2,711 participants, 1,572 (58.0%) reported aspirin non-use; of these, 1,433 and 1,437 had 11dTxB2 and sCD40L measured, respectively. Over a median 6.6 years, a two-fold higher baseline 11dTxB2 was associated with increased rates of total (8.8%; 95%CI: 0.4-17.8%) and severe (18.1%; 95%CI: 5.1-32.6%) exacerbations. Although there were no significant interactions, there was a trend toward higher severe exacerbation rates among current cigarettes smokers and those with COPD. There were no significant results for sCD40L. Among aspirin non-users, higher 11dTxB2, but not sCD40L, was associated with worse cross-sectional respiratory health and modestly increased all-cause mortality over a median 8.2 years (adjusted hazard ratio 1.11; 95%CI: 1.00-1.24). After covariate adjustment, there were no associations with longitudinal respiratory health or cause-specific mortality. CONCLUSIONS: Systemic platelet activation, measured by urinary 11dTxB2, is a statistically significant but modest predictor of respiratory exacerbations and all-cause mortality in individuals with or at risk for COPD, suggesting its potential utility as a prognostic and predictive biomarker for antiplatelet therapy trials. CLINICAL TRIAL REGISTRATION: NCT01969344.

aspirin↗