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Jadwiga A Wedzicha

Publications and source records attributed to Jadwiga A Wedzicha.

At least 19 recordsLinked to original sources
PubMed2024

Design of the SPIROMICS Study of Early COPD Progression: SOURCE Study.

BACKGROUND: The biological mechanisms leading some tobacco-exposed individuals to develop early-stage chronic obstructive pulmonary disease (COPD) are poorly understood. This knowledge gap hampers development of disease-modifying agents for this prevalent condition. OBJECTIVES: Accordingly, with National Heart, Lung and Blood Institute support, we initiated the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) Study of Early COPD Progression (SOURCE), a multicenter observational cohort study of younger individuals with a history of cigarette smoking and thus at-risk for, or with, early-stage COPD. Our overall objectives are to identify those who will develop COPD earlier in life, characterize them thoroughly, and by contrasting them to those not developing COPD, define mechanisms of disease progression. METHODS/DISCUSSION: SOURCE utilizes the established SPIROMICS clinical network. Its goal is to enroll n=649 participants, ages 30-55 years, all races/ethnicities, with ≥10 pack-years cigarette smoking, in either Global initiative for chronic Obstructive Lung Disease (GOLD) groups 0-2 or with preserved ratio-impaired spirometry; and an additional n=40 never-smoker controls. Participants undergo baseline and 3-year follow-up visits, each including high-resolution computed tomography, respiratory oscillometry and spirometry (pre- and postbronchodilator administration), exhaled breath condensate (baseline only), and extensive biospecimen collection, including sputum induction. Symptoms, interim health care utilization, and exacerbations are captured every 6 months via follow-up phone calls. An embedded bronchoscopy substudy involving n=100 participants (including all never-smokers) will allow collection of lower airway samples for genetic, epigenetic, genomic, immunological, microbiome, mucin analyses, and basal cell culture. CONCLUSION: SOURCE should provide novel insights into the natural history of lung disease in younger individuals with a smoking history, and its biological basis.

SPIROMICS↗
PubMed2006

Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease.

IMPACT: This study explores the use of measuring plasma biomarkers at exacerbation of chronic obstructive pulmonary disease (COPD), providing insight into the underlying pathogenesis of these important events. RATIONALE: The use of measuring C-reactive protein (CRP) to confirm exacerbation, or to assess exacerbation severity, in COPD is unclear. Furthermore, it is not known whether there may be more useful systemic biomarkers. OBJECTIVE: To assess the use of plasma biomarkers in confirming exacerbation and predicting exacerbation severity. METHODS: We assessed 36 biomarkers in 90 paired baseline and exacerbation plasma samples from 90 patients with COPD. The diagnosis of exacerbation fulfilled both health care use and symptom-based criteria. Biomarker concentrations were related to clinical indices of exacerbation severity. Interrelationships between biomarkers were examined to gain information on mechanisms of systemic inflammation at exacerbation of COPD. MEASUREMENTS AND MAIN RESULTS: To confirm the diagnosis of exacerbation, the most selective biomarker was CRP. However, this was neither sufficiently sensitive nor specific alone (area under the receiver operating characteristic curve [AUC], 0.73; 95% confidence interval, 0.66-0.80). The combination of CRP with any one increased major exacerbation symptom recorded by the patient on that day (dyspnea, sputum volume, or sputum purulence) significantly increased the AUC to 0.88 (95% confidence interval, 0.82-0.93; p<0.0001). There were no significant relationships between biomarker concentrations and clinical indices of exacerbation severity. Interrelationships between biomarkers suggest that the acute-phase response is related, separately, to monocytic and lymphocytic-neutrophilic pathways. CONCLUSIONS: Plasma CRP concentration, in the presence of a major exacerbation symptom, is useful in the confirmation of COPD exacerbation. Systemic biomarkers were not helpful in predicting exacerbation severity. The acute-phase response at exacerbation was most strongly related to indices of monocyte function.

Aged↗
PubMed2006

Respiratory syncytial virus, airway inflammation, and FEV1 decline in patients with chronic obstructive pulmonary disease.

BACKGROUND: Respiratory syncytial virus (RSV) is increasingly recognized as an important pathogen in adults with cardiopulmonary disease. It has been associated with acute exacerbations of chronic obstructive pulmonary disease (COPD); however, it has also been detected in the lower airway in the stable state, but the consequences of RSV in stable disease have not previously been determined. We therefore studied the consequences of RSV persistence in adults with COPD and its effect on airway inflammation and lung function decline. METHODS: A total of 241 sputum samples from 74 patients with COPD (FEV(1)% predicted, 39.2%; interquartile range, 29.6-57.8%) were collected quarterly in the stable state over 2 yr. RSV was detected by polymerase chain reaction (PCR), quantitative microbiology was performed, and inflammatory cytokines were quantified by ELISA. RESULTS: RSV RNA was detected in 32.8% of sputum samples. Patients in whom RSV was more frequently detected (> 50% of samples RSV PCR-positive, n=18) had higher airway inflammation and faster FEV(1) decline over the study (101.4 ml/yr [95% confidence interval, 57.1-145.8]) compared with those with less frequent detection of RSV (n=56; 51.2 ml/yr [31.7-70.8]; p=0.01). The observed relationship between RSV detection and accelerated lung function decline was independent of smoking status, exacerbation frequency, and lower airway bacterial load. CONCLUSIONS: Persistent RSV detection in patients with COPD is associated with airway inflammation and accelerated decline in FEV(1). Chronic RSV infection may be a novel therapeutic target to alter the natural history of COPD.

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PubMed2006

Nasal symptoms, airway obstruction and disease severity in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by inflammation of the lung in association with airflow obstruction. There is increasing evidence of upper airway involvement in COPD and we have reported that this nasal inflammation is proportional to that in the lung. Given recognized relationships between lower airway inflammation and spirometric indices such as the Forced Expiratory Volume in one second (FEV(1)), we hypothesized that there may be a relationship between nasal obstruction and FEV(1) in COPD. We also sought to investigate relationships between nasal symptoms and nasal patency in COPD. METHODS: We assessed the nasal and pulmonary airways, using acoustic rhinometry and spirometry respectively, in 51 patients with COPD. RESULTS: The presence of chronic nasal symptoms in COPD was associated with reduced nasal patency (6.04 cm(2) symptoms vs. 9.55 cm(2) no symptoms, at the second minimum cross-sectional area, P = 0.049). Nasal patency in COPD was inversely proportional to pulmonary airflow obstruction, and therefore to COPD disease severity (e.g. FEV(1)% predicted vs. second minimum cross-sectional area, r = 0.36, P = 0.009). CONCLUSIONS: The degree of nasal airway obstruction in COPD reflects the impairment to pulmonary airflow, and is greater in the presence of chronic nasal symptoms. This study provides further evidence of pan-airway involvement in COPD.

Aged↗
PubMed2006

Effect of interactions between lower airway bacterial and rhinoviral infection in exacerbations of COPD.

STUDY OBJECTIVES: The inflammatory responses and associated clinical severity of COPD exacerbations are greatly variable, and the determinants of these factors are poorly understood. We examined the hypothesis that bacteria and viruses may modulate this heterogeneity and that interactions between bacterial and viral infection may affect changes in airway bacterial load and the clinical features and inflammatory responses of exacerbations in patients with COPD. DESIGN: Prospective cohort study. SETTING: Outpatient Department, London Chest Hospital, London, UK. PATIENTS: Thirty-nine patients with COPD. MEASUREMENTS: We prospectively studied 56 COPD exacerbations, obtaining clinical data and paired sputum and serum samples at baseline and exacerbation. Qualitative and quantitative microbiology, polymerase chain reaction detection for rhinovirus, and estimation of cytokine levels by enzyme-linked immunosorbent assay were performed. RESULTS: A total of 69.6% of exacerbations were associated with a bacterial pathogen, most commonly Haemophilus influenzae. Rhinovirus was identified in 19.6% of exacerbations. The rise in bacterial load at exacerbation correlated with the rise in sputum interleukin (IL)-8 (r = 0.37, p = 0.022) and fall in FEV1 (r = 0.35, p = 0.048). Exacerbations with both rhinovirus and H. influenzae had higher bacterial loads (10(8.56) cfu/mL vs 10(8.05)cfu/mL, p = 0.018) and serum IL-6 (13.75 pg/mL vs 6.29 pg/mL, p = 0.028) than exacerbations without both pathogens. In exacerbations with both cold symptoms (a marker of putative viral infection) and a bacterial pathogen, the FEV1 fall was greater (20.3% vs 3.6%, p = 0.026) and symptom count was higher (p = 0.019) than those with a bacterial pathogen alone. CONCLUSIONS: The clinical severity and inflammatory responses in COPD exacerbations are modulated by the nature of the infecting organism: bacterial and viral pathogens interact to cause additional rises in inflammatory markers and greater exacerbation severity.

Aged↗
PubMed2006

Impact of chronic obstructive pulmonary disease exacerbations on patients and payers.

Chronic obstructive pulmonary disease (COPD) is not only an established major cause of mortality and morbidity but is increasing in worldwide prevalence despite current medical interventions. The natural history of COPD is punctuated by periods of acute symptomatic, physiologic, and functional deterioration or exacerbations. These events are responsible for considerable additional morbidity and mortality and impact on patients' long-term health status. Despite advances in understanding disease mechanisms and in treatment, exacerbations continue to be the major cause of COPD-associated hospitalization, and provision for their management incurs considerable health care costs. Although pharmacologic therapies may improve clinical outcomes, these benefits must be optimized by prompt diagnosis and delivery. This will require improved understanding of this complex disease by physicians and patients alike.

Disease Progression↗
PubMed2005

Systemic and upper and lower airway inflammation at exacerbation of chronic obstructive pulmonary disease.

RATIONALE: In addition to pulmonary involvement, stable chronic obstructive pulmonary disease (COPD) is associated with nasal and systemic inflammation. Although exacerbations of COPD are associated with increased pulmonary and systemic inflammation, determinants of the systemic response remain obscure, and nor is it known whether there is nasal involvement. OBJECTIVES: To investigate upper airway, lower airway, and systemic inflammation at exacerbation of COPD. METHODS: We sampled sputum, nasal wash, and serum from 41 exacerbations (East London cohort) for analysis of pathogenic microorganisms and inflammatory indices (sputum/nasal wash leukocytes, interleukin [IL]-6, IL-8, and myeloperoxidase; serum IL-6 and C-reactive protein). Values were compared with stable COPD. MEASUREMENTS AND MAIN RESULTS: Exacerbation of COPD is associated with greater nasal, sputum, and serum inflammation than the stable state. At exacerbation, inflammatory markers were highly correlated within nasal wash and serum (all r >/= 0.62, p < 0.001), but not sputum. The degree of upper airway inflammation correlated with the degree of lower airway inflammation (e.g., nasal wash/sputum myeloperoxidase; r = 0.50, p = 0.001). The degree of systemic inflammation correlated with the degree of lower airway inflammation (e.g., serum IL-6/sputum IL-8; r = 0.35, p = 0.026), and was greater in the presence of a sputum bacterial pathogen (29.0 g/dl C-reactive protein difference, p = 0.002). We did not find relationships between the upper airway and systemic compartments. CONCLUSIONS: Exacerbation of COPD is associated with pan-airway inflammation; the systemic inflammatory response is proportional to that occurring in the lower airway and greater in the presence of a bacterial pathogen.

Aged↗
PubMed2005

Effectiveness of innovations in nurse led chronic disease management for patients with chronic obstructive pulmonary disease: systematic review of evidence.

OBJECTIVE: To determine the effectiveness of innovations in management of chronic disease involving nurses for patients with chronic obstructive pulmonary disease (COPD). DESIGN: Systematic review of randomised controlled trials. DATA SOURCES: 24 electronic databases searched for English or Dutch language studies published between January 1980 and January 2005. REVIEW METHODS: Included studies described inpatient, outpatient, and community based interventions for chronic disease management that were led, coordinated, or delivered by nurses. Hospital at home and early discharge schemes for acute exacerbations of COPD were excluded. RESULTS: We identified nine relevant randomised controlled trials, most of which had some potential methodological flaws. All the interventions seemed to be variations on a case management model. The interventions described could be divided into brief (one month) and longer term (around a year) or more intensive interventions. Only two studies examined the effect of brief interventions, these found little evidence of any benefit. Meta-analysis of the long term interventions failed to detect any influence on mortality at 9-12 months' follow-up (Peto odds ratio 0.85, 95% confidence interval 0.58 to 1.26). There was evidence that the long term interventions had not improved patients' health related quality of life, psychological wellbeing, disability, or pulmonary function. The evidence on whether long term interventions reduced readmissions to hospital was equivocal, but the only study exclusively directed at patients on long term oxygen therapy reported a reduction in readmission. We identified several outcomes where little or no evidence was available; these included patients' satisfaction, self management skills, adherence with treatment recommendations, the likelihood of smoking cessation, and the effect of the interventions on carers. CONCLUSION: There is little evidence to date to support the widespread implementation of nurse led management interventions for COPD, but the data are too sparse to exclude any clinically relevant benefit or harm arising from such interventions.

Adult↗
PubMed2005

Relationships among bacteria, upper airway, lower airway, and systemic inflammation in COPD.

STUDY OBJECTIVE: The upper and lower airways are continuous. While upper airway symptoms are common in COPD patients, with accumulating evidence to suggest increased nasal inflammation, the relationships among upper airway, lower airway, and systemic inflammatory indexes have not been studied. We aimed to confirm that there is heightened nasal inflammation in COPD patients, to test the hypothesis that the degree of upper airway inflammation relates to the degree of lower airway inflammation, and to investigate the underlying associations with bacterial carriage and the systemic inflammatory response. DESIGN: Prospective cohort study. SETTING: Outpatient Department, London Chest Hospital, London, UK. PARTICIPANTS: Forty-seven patients with COPD and 12 control subjects of similar age, sex, and smoking status. MEASUREMENTS: Serum, nasal wash fluid, and sputum samples were obtained from 47 stable patients with COPD for the analysis of inflammatory indexes and bacterial colonization. Nasal wash fluid specimens were obtained from 12 control subjects. RESULTS: COPD patients had an increased nasal interleukin (IL)-8 concentration compared to control subjects (difference, 97.2 pg/mL; p = 0.009). The nasal IL-8 concentration in COPD patients correlated with that in sputum (r = 0.30; p = 0.039). In both the upper and lower airways of patients with COPD, the IL-8 concentration was associated with indexes of bacterial colonization. Patients colonized with a sputum potentially pathogenic microorganism had a higher total nasal bacterial load (difference, 1.5 log cfu/mL; p = 0.016). We did not find significant relationships between the degree of upper or lower airway inflammation, or bacterial carriage, and the systemic inflammatory response. CONCLUSIONS: COPD is associated with an increased nasal concentration of the neutrophil chemoattractant protein IL-8, the degree of which reflects that present in the lower airway. A relationship between lower airway bacterial colonization, postnasal drip, and higher nasal bacterial load may suggest a mechanism underlying this finding. This study is the first to report a correlation between the degree of upper and lower airway inflammation in COPD.

Aged↗
PubMed2005

Airway and systemic inflammation and decline in lung function in patients with COPD.

STUDY OBJECTIVES: Patients with COPD experience lower airway and systemic inflammation, and an accelerated decline in FEV1. There is no evidence on whether this inflammation changes over time, or if it is associated with a faster decline in FEV1. PATIENTS AND DESIGN: A cohort of 148 COPD patients (100 men) was monitored daily for a median of 2.91 years (interquartile range [IQR], 2.1 to 4.8). At recruitment, median age was 68.5 years (IQR, 62.5 to 73.6) and FEV1 as percentage of predicted (FEV1%Pred) was 38.5% (IQR, 27.7 to 50.3). RESULTS: During the study, the patients experienced 1,389 exacerbations, a median of 2.52/yr (IQR, 1.48 to 3.96) and FEV1 declined by 40.2 mL/yr or as FEV1%Pred by 1.5%/yr. Concerning inflammatory markers, sputum interleukin (IL)-6 rose by 9 pg/mL/yr, sputum neutrophil count rose by 1.64 x 10(6) cells per gram sputum per year, an plasma fibrinogen rose by 0.10 g/L/yr (all p < 0.05). Patients with frequent exacerbations (> or = 2.52/yr) had a faster rise over time in plasma fibrinogen and sputum IL-6 of 0.063 g/L/yr (p = 0.046, n = 130) and 29.5 pg/mL/yr (p < 0.001, n = 98), respectively, compared to patients with infrequent exacerbations (< 2.52/yr). Using the earliest stable (nonexacerbation) measured marker, patients whose IL-6 exceeded the group median had a faster FEV1%Pred decline of 0.42%/yr (p = 0.018). Similarly, a high neutrophil count or fibrinogen were associated with a faster FEV1%Pred decline of 0.97%/yr (p = 0.001) and 0.40%/yr (p = 0.014), respectively. CONCLUSIONS: In COPD, airway and systemic inflammatory markers increase over time; high levels of these markers are associated with a faster decline in lung function.

Aged↗
PubMed2004

Exacerbations and time spent outdoors in chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease have a progressive reduction in activity, although its time scale and the contribution of exacerbations are unknown. A rolling cohort of 147 patients (101 male; mean age, 88.5 years; and forced expiratory volume in 1 second as percent predicted, 38.4%) were monitored for a median of 1,044 days (interquartile range, 685 to 1,779) over an 8-year period starting in March 1996. Patients recorded any increase in daily respiratory symptoms and time spent outside their home. They completed the St. George's Respiratory Questionnaire yearly. They experienced 1,465 exacerbations and time outdoors decreased by -0.16 hours/day per year (p < 0.001). This decline was faster in frequent exacerbators (p = 0.011). Before exacerbation, the patients stayed indoors all day for 2.1 days/week (on any day 34.1% were at home), but for 5 weeks postexacerbation they spent 2.5 days/week at home (p < 0.001) (44.4% remaining at home at onset; p = 0.021). St. George's total, activity, and impact scores were independently associated with time outdoors (p < 0.005), but not with symptom score. In conclusion, time spent outside the home declines over time and acutely at exacerbation. Patients with frequent exacerbations are more likely to become housebound and need targeting in rehabilitation programs.

Activities of Daily Living↗
PubMed2004

Hospital at home for patients with acute exacerbations of chronic obstructive pulmonary disease: systematic review of evidence.

OBJECTIVES: To evaluate the efficacy of hospital at home schemes compared with inpatient care in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD). DESIGN: A systematic review of randomised controlled trials. MAIN OUTCOME MEASURE: Mortality and readmission to hospital. RESULTS: Seven trials with 754 patients were included in the review. Hospital readmission and mortality were not significantly different when hospital at home schemes were compared with inpatient care (relative risk 0.89, 95% confidence interval 0.72 to 1.12, and 0.61, 0.36 to 1.05, respectively). However, compared with inpatient care, hospital at home schemes were associated with substantial cost savings as well as freeing up hospital inpatient beds. CONCLUSIONS: Hospital at home schemes can be safely used to care for patients with acute exacerbations of COPD who would otherwise be admitted to hospital. Clinicians should consider this form of management, especially as there is increasing pressure for inpatient beds in the United Kingdom.

Acute Disease↗
PubMed2004

Bronchiectasis, exacerbation indices, and inflammation in chronic obstructive pulmonary disease.

Relationships between high-resolution computed tomography (HRCT) findings in chronic obstructive pulmonary disease (COPD) and bacterial colonization, airway inflammation, or exacerbation indices are unknown. Fifty-four patients with COPD (mean [SD]: age, 69 [7] years; FEV(1), 0.96 [0.33] L; FEV(1) [percent predicted], 38.1 [13.9]%; FEV(1)/forced vital capacity [percent predicted], 40.9 [11.8]%; arterial partial pressure of oxygen, 8.77 [1.11] kPa; history of smoking, 50.5 [33.5] smoking pack-years) underwent HRCT scans of the chest to quantify the presence and extent of bronchiectasis or emphysema. Exacerbation indices were determined from diary cards over 2 years. Quantitative sputum bacteriology and cytokine measurements were performed. Twenty-seven of 54 patients (50%) had bronchiectasis on HRCT, most frequently in the lower lobes (18 of 54, 33.3%). Patients with bronchiectasis had higher levels of airway inflammatory cytokines (p = 0.001). Lower lobe bronchiectasis was associated with lower airway bacterial colonization (p = 0.004), higher sputum interleukin-8 levels (p = 0.001), and longer symptom recovery time at exacerbation (p = 0.001). No relationship was seen between exacerbation frequency and HRCT changes. Evidence of moderate lower lobe bronchiectasis on HRCT is common in COPD and is associated with more severe COPD exacerbations, lower airway bacterial colonization, and increased sputum inflammatory markers.

Aged↗
PubMed2004

Early therapy improves outcomes of exacerbations of chronic obstructive pulmonary disease.

Treatment of chronic obstructive pulmonary disease (COPD) exacerbations improves outcomes; however, responses to treatment are variable, and patients with COPD often delay presentation or fail to seek therapy. The impact on exacerbation outcomes, hospitalization, and health status of delaying or failing to seek treatment is poorly understood. We studied between 1996 and 2002 a cohort of 128 patients with COPD, mean (SD) FEV(1) of 1.07 (0.43) L. Patients recorded respiratory symptoms daily and reported exacerbations to the outpatient-based study team or to their primary care physician; 1,099 exacerbations were recorded by the patients, of which 658 were reported to a physician. The time between exacerbation onset and treatment was a median (interquartile range) of 3.69 (2.0-5.57) days, and the exacerbation recovery time was 10.7 (7.0-14.0) days. Earlier treatment was associated with a faster recovery (regression coefficient 0.42 days/day delay) (confidence interval, 0.19-0.65; p < 0.001). Patients who reported a higher proportion of exacerbations for treatment had better health-related quality of life than those patients with more untreated exacerbations (rho = -0.22, p = 0.018). Failure to report exacerbations was associated with an increased risk of emergency hospitalization (rho = 0.21, p = 0.04). Patient recognition of exacerbation symptoms and prompt treatment improves exacerbation recovery, reduces risks of hospitalization, and is associated with a better health-related quality of life.

Aged↗
PubMed2004

Upper airway symptoms and quality of life in chronic obstructive pulmonary disease (COPD).

OBJECTIVE: To assess the impact on quality of life from upper airway symptoms in chronic obstructive pulmonary disease (COPD). METHODS: Sixty-five patients with moderate-to-severe COPD were studied using the 20-item Sino-Nasal Outcome Test (SNOT-20) questionnaire, a validated disease-specific health-related quality of life tool for the assessment of rhinosinusitis. Patients also completed the St. George's Respiratory Questionnaire (SGRQ). RESULTS: Eighty-eight percent of patients experienced nasal symptoms on most days of the week, most commonly rhinorrhoea. The mean SNOT-20 score of 1.24 demonstrates that nasal symptoms cause impairment to quality of life. The SNOT-20 score correlated with the number of chronic nasal symptoms (rho = 0.51, P < 0.01): the more daily nasal symptoms experienced, the greater the impact on health status. There was no significant correlation between SNOT-20 and SGRQ (r = 0.21, P = 0.09) suggesting that both upper and lower airway symptoms contribute to the total quality of life burden. CONCLUSIONS: This is the first study to report on upper airway involvement in well characterised COPD patients using a previously validated assessment tool. Upper airway symptoms are frequent in these patients and cause impairment to the quality of life. These effects may not be detected using currently available quality of life tools that focus on lower respiratory tract symptoms.

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