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Biomedical subjects

J A Wedzicha

Publications and source records attributed to J A Wedzicha.

At least 19 recordsLinked to original sources
PubMed2001

Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease.

The effects of respiratory viral infection on the time course of chronic obstructive pulmonary disease (COPD) exacerbation were examined by monitoring changes in systemic inflammatory markers in stable COPD and at exacerbation. Eighty-three patients with COPD (mean [SD] age, 66.6 [7.1] yr, FEV(1), 1.06 [0.61] L) recorded daily peak expiratory flow rate and any increases in respiratory symptoms. Nasal samples and blood were taken for respiratory virus detection by culture, polymerase chain reaction, and serology, and plasma fibrinogen and serum interleukin-6 (IL-6) were determined at stable baseline and exacerbation. Sixty-four percent of exacerbations were associated with a cold occurring up to 18 d before exacerbation. Seventy-seven viruses (39 [58.2%] rhinoviruses) were detected in 66 (39.2%) of 168 COPD exacerbations in 53 (64%) patients. Viral exacerbations were associated with frequent exacerbators, colds with increased dyspnea, a higher total symptom count at presentation, a longer median symptom recovery period of 13 d, and a tendency toward higher plasma fibrinogen and serum IL-6 levels. Non-respiratory syncytial virus (RSV) respiratory viruses were detected in 11 (16%), and RSV in 16 (23.5%), of 68 stable COPD patients, with RSV detection associated with higher inflammatory marker levels. Respiratory virus infections are associated with more severe and frequent exacerbations, and may cause chronic infection in COPD. Prevention and early treatment of viral infections may lead to a decreased exacerbation frequency and morbidity associated with COPD.

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PubMed2001

Mechanisms of exacerbations.

Exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of morbidity and mortality and hospital admission. Some patients are particularly susceptible to develop frequent exacerbations; exacerbation frequency being an important determinant of health related quality of life. Patients with frequent exacerbations (three or more exacerbations per year) have increased induced sputum cytokine interleukin (IL)-6 and IL-8 levels when stable, suggesting that frequent exacerbation is associated with increased airway inflammatory changes. Respiratory viral infections are a major cause of COPD exacerbations, with upper respiratory tract infections (colds) being associated with two-thirds of COPD exacerbations. Rhinovirus has been detected in induced sputum by PCR in 25% of exacerbations, suggesting that rhinovirus may directly infect the lower airway triggering exacerbation. The presence of an upper respiratory tract infection leads to a longer symptom recovery time at exacerbation. At exacerbation induced sputum IL-6 levels were increased compared to stable, though there were no significant increases in IL-8 or sputum cell counts. Sputum IL-6 levels were found to be higher in those patients with symptoms of a common cold. Increased airway eosinophilia has been also found at exacerbation. Other factors including bacterial colonization of the airways, temperature and interactions with environmental pollutants may also play a role in COPD exacerbation.

Animals↗
PubMed2001

Sputum and plasma endothelin-1 levels in exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Endothelin (ET)-l is a bronchoconstrictor peptide produced in the airways. It has been implicated in the pathogenesis of asthma and virally mediated airway inflammation and may play a role in exacerbations of chronic obstructive pulmonary disease (COPD). METHODS: Seventy one patients with COPD were followed prospectively and sampled for plasma and sputum ET-1 levels when stable and during an exacerbation. Sputum was also examined for cytokines, human rhinovirus, and Chlamydia pneumoniae. RESULTS: Plasma ET-1 levels were available for 67 patients with stable COPD (mean (SD) 0.58 (0.31) pg/ml); 28 pairs of stable-exacerbation plasma samples had a mean stable ET-1 level of 0.54 (0.30) pg/ml rising to 0.67 (0.35) pg/ml at exacerbation (mean difference 0.13, 95% confidence interval (CI) 0.04 to 0.21, p = 0.004). Plasma ET-1 levels in the 67 patients with stable COPD were inversely correlated with baseline forced expiratory volume in one second (FEV(1); r = -0. 29, p = 0.022) and forced vital capacity (FVC; r = -0.38, p = 0.002). The change in plasma ET-1 levels during an exacerbation correlated with the change in oxygen saturation (SaO(2); r = -0.41, p = 0.036). In 14 stable-exacerbation pairs of sputum samples median stable ET-1 levels were 5.37 (0.97-21.95) pg/ml rising to 34.68 (13.77-51.95) pg/ml during an exacerbation (mean difference 25.14, 95% CI 3.77 to 46.51, p = 0.028). This increase in sputum ET-1 levels correlated with the increase in plasma ET-1 levels (r = 0.917, p = 0.001) and sputum interleukin (IL)-6 levels (r = 0.718, p = 0.013). CONCLUSIONS: Sputum levels of ET-1 rise in COPD patients during an exacerbation and this is reflected by a smaller rise in plasma ET-1 levels. ET-1 may have a role in mediating airway inflammatory changes during exacerbations of COPD.

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PubMed2000

Detection of rhinovirus in induced sputum at exacerbation of chronic obstructive pulmonary disease.

Common colds are associated with exacerbations of chronic obstructive pulmonary disease (COPD). However, the role of the common cold virus (human rhinovirus) in the production of symptoms and lower airway inflammation at COPD exacerbation is unknown. Thirty three patients with moderate-to-severe COPD were seen at baseline, when the number of chest infections in the previous year was noted, and acutely at COPD exacerbation. Within 48 h after the onset of the exacerbation and at baseline, nasal aspirates and induced sputum were taken for rhinovirus reverse transcriptase polymerase chain reaction (RT-PCR) analysis and determination of cytokine levels. Symptoms, recorded on diary cards, were noted and forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) measured. At exacerbation, mean FEV1 and FVC fell significantly from baseline (p<0.001). Ten of 43 exacerbations were associated with rhinovirus infection, detected in induced sputum. In four of these, nasopharyngeal samples contained no detectable rhinovirus. All baseline samples were negative for rhinovirus. The simultaneous presence of increased nasal discharge/nasal congestion (in 26 of the 43 exacerbations) and increased sputum (29 exacerbations) was strongly associated with the presence of rhinovirus (odds ratio 6.15; p=0.036). Total symptom scores were greater for rhinovirus as compared to nonrhinovirus exacerbations (p=0.039). Median baseline sputum interleukin-6 levels rose from 90.2 to 140.3 pg x mL(-1) at exacerbation (p=0.005); the change was greater in the presence of rhinovirus infection (p=0.008). Rhinovirus infection can be detected at chronic obstructive pulmonary disease exacerbation. This is associated with elevation of lower airway interleukin-6 levels, which may mediate lower airway symptom expression during chronic obstructive pulmonary disease exacerbations.

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PubMed2000

Development and validation of a standardized measure of activity of daily living in patients with severe COPD: the London Chest Activity of Daily Living scale (LCADL).

Activities of daily living (ADL) may be severely restricted in patients with COPD and assessment requires evaluation of the impact of disability and handicap on daily life. This study is concerned with the development and validation of a standardized 15-item questionnaire to assess routine ADL. Sixty (33 male, 27 female) patients with severe COPD, mean (SD) FEV1 0.91 (0.43) l, median (range) age 70 (50-82) years, completed a 59-item ADL list previously generated by open-ended interview and by literature review. Patients also performed the Shuttle Walk Test (SWT), and completed the St George's Respiratory Questionnaire (SGRQ), the Nottingham Extended Activity of Daily Living Questionnaire (EADL) and the Hospital Anxiety and Depression score (HAD). Criteria for item reduction in the development of The London Chest ADL scale (LCADL) consisted of removal of items where the majority of respondents showed no limitation in the activity (n = 19), where there was no association with perception of global health (n = 9), where an association with age or gender was detected (n = 4), or where items showed poor reliability on test re-test (n = 9). Fifteen items were identified as core activities of daily living. The LCADL was then compared with other measures of health status in these patients. There were good correlations with the SGRQ activity and impact components (p=0.70; P<0.0001) and (p=0.58; P<0.0001), respectively, and EADL (p=0.45; P<0.001), and a moderate correlation with HAD anxiety (p=0.28; P<0.03). There was a significant relationship between the SWT and LCADL (p=0.58; P<0.0001), suggesting a relationship between impaired exercise performance and lower ADL scores. There was evidence of high internal consistency of the questionnaire with Chronbach's alpha of 0.98. These findings suggest that the LCADL scale is a valid tool for the assessment of ADL in patients with severe COPD.

Activities of Daily Living↗
PubMed2000

Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations.

BACKGROUND: Although it is presumed that exacerbations of chronic obstructive pulmonary disease (COPD) are associated with increased airway inflammation, there is little information available on inflammatory markers during an exacerbation and the relationship with severity or time course of recovery. A study was undertaken to investigate the sputum cell and cytokine characteristics of COPD when stable and during an exacerbation. METHODS: Induced sputum samples from 57 patients with moderate to severe COPD were analysed (44 samples were taken during a stable period and 37 during an exacerbation). The patients recorded daily symptoms on diary cards. Cell counts and sputum levels of interleukin (IL)-6 and IL-8 were measured. RESULTS: Patients with >/=3 exacerbations/year had higher median stable sputum levels of IL-6 (110 (95% CI 11 to 215) pg/ml) and IL-8 (6694 (95% CI 3120 to 11995) pg/ml) than those with </=2 exacerbations/year (22 (95% CI 12 to 93) and 1628 (95% CI 607 to 4812) pg/ml, respectively). Median IL-6 levels were increased during exacerbations compared with stable conditions. The levels of IL-6 during exacerbations were related to the presence of a cold and to the total cell count and eosinophil and lymphocyte numbers, while IL-8 was positively correlated with all sputum cell counts. Sputum cell counts and cytokine levels during an exacerbation did not predict the size and duration of lung function changes in the exacerbation. CONCLUSIONS: Patients with more frequent exacerbations have higher baseline sputum cytokine levels, which may predict the frequency of future exacerbations.

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PubMed2000

Supplemental oxygen during pulmonary rehabilitation in patients with COPD with exercise hypoxaemia.

BACKGROUND: Supplemental oxygen in patients with chronic obstructive pulmonary disease (COPD) and exercise hypoxaemia improves exercise capacity and dyspnoea. However, the benefit of oxygen during pulmonary rehabilitation in these patients is still unknown. METHODS: Twenty five patients with stable COPD (mean (SD) forced expiratory volume in one second (FEV(1)) 0.76 (0.29) l and 30.0 (9.89)% predicted, arterial oxygen tension (PaO(2)) 8.46 (1.22) kPa, arterial carbon dioxide tension (PaCO(2)) 6.32 (1.01) kPa) and significant arterial desaturation on exercise (82.0 (10.4)%) were entered onto a pulmonary rehabilitation programme. Patients were randomised to train whilst breathing oxygen (OT) (n = 13) or air (AT) (n = 12), both at 4 l/min. Assessments included exercise tolerance and associated dyspnoea using the shuttle walk test (SWT) and Borg dyspnoea score, health status, mood state, and performance during daily activities. RESULTS: The OT group showed a significant reduction in dyspnoea after rehabilitation compared with the AT group (Borg mean difference -1.46 (95% CI -2.72 to -0.19)) but there were no differences in other outcome measures: SWT difference -23.6 m (95% CI -70.7 to 23.5), Chronic Respiratory Disease Questionnaire 3.67 (95% CI -7.70 to 15.1), Hospital Anxiety and Depression Scale 1. 73 (95% CI -2.32 to 5.78), and London Chest Activity of Daily Living Scale -2.18 (95% CI -7.15 to 2.79). At baseline oxygen significantly improved SWT (mean difference 27.3 m (95% CI 14.7 to 39.8) and dyspnoea (-0.68 (95% CI -1.05 to -0.31)) compared with placebo air. CONCLUSIONS: This study suggests that supplemental oxygen during training does little to enhance exercise tolerance although there is a small benefit in terms of dyspnoea. Patients with severe disabling dyspnoea may find symptomatic relief with supplemental oxygen.

Activities of Daily Living↗
PubMed2000

Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease.

Although exacerbations of chronic obstructive pulmonary disease (COPD) are associated with symptomatic and physiological deterioration, little is known of the time course and duration of these changes. We have studied symptoms and lung function changes associated with COPD exacerbations to determine factors affecting recovery from exacerbation. A cohort of 101 patients with moderate to severe COPD (mean FEV(1) 41.9% predicted) were studied over a period of 2.5 yr and regularly followed when stable and during 504 exacerbations. Patients recorded daily morning peak expiratory flow rate (PEFR) and changes in respiratory symptoms on diary cards. A subgroup of 34 patients also recorded daily spirometry. Exacerbations were defined by major symptoms (increased dyspnea, increased sputum purulence, increased sputum volume) and minor symptoms. Before onset of exacerbation there was deterioration in the symptoms of dyspnea, sore throat, cough, and symptoms of a common cold (all p < 0.05), but not lung function. Larger falls in PEFR were associated with symptoms of increased dyspnea (p = 0.014), colds (p = 0.047), or increased wheeze (p = 0.009) at exacerbation. Median recovery times were 6 (interquartile range [IQR] 1 to 14) d for PEFR and 7 (IQR 4 to 14) d for daily total symptom score. Recovery of PEFR to baseline values was complete in only 75.2% of exacerbations at 35 d, whereas in 7.1% of exacerbations at 91 d PEFR recovery had not occurred. In the 404 exacerbations where recovery of PEFR to baseline values was complete at 91 d, increased dyspnea and colds at onset of exacerbation were associated with prolonged recovery times (p < 0.001 in both cases). Symptom changes during exacerbation do not closely reflect those of lung function, but their increase may predict exacerbation, with dyspnea or colds characterizing the more severe. Recovery is incomplete in a significant proportion of COPD exacerbations.

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PubMed2000

Randomized controlled trial of domiciliary noninvasive positive pressure ventilation and physical training in severe chronic obstructive pulmonary disease.

The addition of noninvasive positive pressure ventilation (NPPV) to an exercise training (ET) program in severe chronic obstructive pulmonary disease (COPD) may produce greater benefits in exercise tolerance and quality of life than after training alone. Forty-five patients with severe stable COPD-mean (SD) FEV(1) 0.96 (0.31) L, Pa(O(2)) 65.4 (9.07) mm Hg, Pa(CO(2)) 45.6 (7.89) mm Hg-were randomized to domiciliary NPPV + ET (n = 23) or ET alone (n = 22). Exercise capacity and health status were assessed at baseline and after an 8-wk training program. There was a significant improvement in mean shuttle walk test (SWT) in the NPPV + ET group: from 169 (112) to 269 (124) m (p = 0.001), compared with the ET group: 205 (100) to 233 (123) m (p = 0.19); mean difference (95% confidence interval [CI]): 72 (12.9 to 131) m. Repeated measures analysis of variance (ANOVA) showed that the differences between the two groups became evident only in the final 4 wk of the training program with a mean end study difference (95% 1CI) of 65.8 (17.1 to 114) m. There was a significant improvement in the Chronic Respiratory Disease Questionnaire (CRDQ) of mean (SD) 24.0 (17.4) (p = < 0.001) in the NPPV + ET group and 11.8 (15.8) (p = 0.003) points in the ET group; mean difference: 12.3 (1.19 to 23.4). Only the NPPV + ET group demonstrated a significant improvement in arterial oxygenation; mean difference: 3.70 mm Hg (0.37 to 7.27). This study suggests that domiciliary NPPV can be used successfully to augment the effects of rehabilitation in severe COPD.

Activities of Daily Living↗
PubMed2000

Long-term oxygen therapy vs long-term ventilatory assistance.

The use of positive-pressure nasal ventilation in combination with LTOT in stable COPD patients with hypercapnic respiratory failure controls hypoventilation and improves daytime ABGs, sleep, and quality of life. Nasal ventilation in COPD is unlikely to produce benefit unless used with supplemental oxygen therapy at night. The patients who show the greatest reduction in overnight PaCO2 with ventilation are the patients most likely to benefit from long-term ventilatory support. Although there is now evidence for short-term benefit from NPPV in hypercapnic COPD, large multicenter studies with survival, exacerbations, and hospital admissions as the primary end points are required to evaluate longer-term effects of this potentially important intervention.

Bronchiectasis↗
PubMed2000

Acute exacerbations of chronic obstructive pulmonary disease are accompanied by elevations of plasma fibrinogen and serum IL-6 levels.

BACKGROUND: Respiratory tract infections may acutely increase risk from coronary heart disease (CHD), though the mechanisms have not been defined. Patients with chronic obstructive pulmonary disease (COPD) are prone to repeated exacerbations that are often associated with respiratory infections. These patients also have increased cardiovascular morbidity and mortality. We hypothesized that transient acute increases in plasma fibrinogen, an independent risk factor for CHD, could occur at COPD exacerbation (mediated through a rise in IL6) and thereby provide a mechanism linking respiratory infection to risk of coronary heart disease. METHODS: 93 COPD patients [mean (SD) age 66.8 (8.1) years] were followed regularly over one year, with daily diary card monitoring of respiratory symptoms and peak expiratory flow rate (PEFR); 67 patients [mean FEV1 1.06 (0.44) l, FVC 2.43 (0.79) l] were seen during 120 exacerbations. At each visit spirometry was measured and blood samples taken for plasma fibrinogen and Interleukin-6 (IL-6) levels. RESULT: At baseline, the mean (SD) plasma fibrinogen was elevated at 3.9 (0.67) g/l in the 67 patients with exacerbations during the study and the median (IQR) IL-6 at 4.3 (2.4 to 6.8) pg/ml. Plasma fibrinogen increased by 0.36 (0.74) g/l at exacerbation (p <0.001). with IL-6 levels rising by 1.10 (-2.73 to 6.95) pg/ml (p = 0.008). There was a relation between the changes in fibrinogen at exacerbation and IL-6 levels (r = 0.348, p <0.001). Multiple regression revealed significantly greater rises in fibrinogen when exacerbations were associated with purulent sputum (b = 0.34 g/l; p = 0.03), increased cough (b = 0.31 g/l, p = 0.019) and symptomatic colds (b = 0.228; p = 0.024). CONCLUSIONS: Plasma fibrinogen levels were elevated in stable patients with COPD and may contribute to the increased cardiovascular morbidity and mortality in these patients. COPD exacerbations increased serum IL-6 levels, leading to a rise in plasma fibrinogen. Thus acute rather than chronic infection may have a role in predisposing to coronary heart disease or stroke.

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PubMed1999

An observational study of inhaled corticosteroid withdrawal in stable chronic obstructive pulmonary disease. ISOLDE Study Group.

Withdrawal of inhaled corticosteroids is known to worsen disease control in bronchial asthma but similar data are lacking in chronic obstructive pulmonary disease (COPD). We hypothesized that clinical exacerbations requiring treatment would occur more often in patients whose inhaled corticosteroids were stopped than in other patients not treated with these agents. We studied 272 patients in mean age 65 (SD 0.8) years, mean FEV1 42.8 (SD 12.6)% predicted, entering the run-in phase of the Inhaled Steroids in Obstructive Lung Disease (ISOLDE) trial. All had been clinically stable for at least 6 weeks and there were no differences in the degree of bronchodilator reversibility, baseline lung function or pack-years of smoking between the 160 patients receiving inhaled corticosteroids and those not so treated. Inhaled corticosteroids were withdrawn in the first week of the study and during the remaining 7 weeks of the study 38% of those previously treated with these drugs had an exacerbation compared to 6% of the chronically untreated group. Patients receiving inhaled corticosteroids reported a longer duration of symptoms but neither this or any other recorded variable predicted the risk of exacerbation. These data suggest that abrupt withdrawal of inhaled corticosteroids should be monitored carefully even in patients with apparently irreversible COPD.

Administration, Inhalation↗
PubMed1999

Adverse effects of nasal continuous positive airway pressure therapy in sleep apnoea syndrome.

Nasal continuous positive airway pressure (nCPAP) is now the treatment of choice for patients with sleep apnoea syndrome. Side-effects and adverse reactions have been described in isolated reports with this device. We have, therefore, systematically studied the side-effects of nCPAP therapy in 300 consecutive patients referred to the London Chest Hospital Ventilatory Support Unit. Ninety-six per cent of patients complained of at least one side-effect resulting from the therapy, with 45 per cent complaining of a side-effect specific to the nasal mask. There was no correlation between the side-effects and level of pressure used during nCPAP. The rate of compliance remained high in spite of the side-effects, with a daily use of 7.8 hours (SD 8.05) and with 83 per cent of the patients using the device every night. Although nCPAP treatment remains acceptable to most patients there exists a high incidence of adverse effects.

Adult↗
PubMed1999

Effect of temperature on lung function and symptoms in chronic obstructive pulmonary disease.

The present study investigated whether falls in environmental temperature increase morbidity from chronic obstructive pulmonary disease (COPD). Daily lung function and symptom data were collected over 12 months from 76 COPD patients living in East London and related to outdoor and bedroom temperature. Questionnaires were administered which asked primarily about the nature of night-time heating. A fall in outdoor or bedroom temperature was associated with increased frequency of exacerbation, and decline in lung function, irrespective of whether periods of exacerbation were excluded. Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) fell markedly by a median of 45 mL (95% percentile range: -113-229 mL) and 74 mL (-454-991 mL), respectively, between the warmest and coolest week of the study. The questionnaire revealed that 10% had bedrooms <13 degrees C for 25% of the year, possibly because only 21% heated their bedrooms and 48% kept their windows open in November. Temperature-related reduction in lung function, and increase in exacerbations may contribute to the high level of cold-related morbidity from chronic obstructive pulmonary disease.

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PubMed1999

Evaluation of pulsed dose oxygen delivery during exercise in patients with severe chronic obstructive pulmonary disease.

BACKGROUND: Oxygen conserving devices may lead to substantial increases in the duration of oxygen provided. A study was undertaken to compare the performance of a pulsed dose oxygen delivery (PDOD) system with continuous flow oxygen or air during a maximal walking test. METHODS: Fourteen patients with chronic obstructive pulmonary disease (COPD) and arterial oxygen desaturation on exercise (mean (SD) forced expiratory volume in one second (FEV1) 0.83 (0.28) 1, arterial oxygen pressure (PaO2) 8.38 (1.24) kPa, arterial carbon dioxide pressure (PaCO2) 5.95 (0.86) kPa) were randomised to perform a walking test using air administered via a cylinder or continuous flow oxygen at 2 l/min or by a PDOD system. RESULTS: There was no significant difference in the mean arterial oxygen saturation (SaO2) using the PDOD system or with continuous flow oxygen (p = 0.33). Patients showed greatest desaturation whilst walking with the air cylinder (SaO2 79.2 (8.59)%) which was significantly different from the desaturation with both continuous flow oxygen (87.6 (5.85)%, p = 0.001) and PDOD (85.6 (7.36)%, p = 0.004). There was no significant difference between the distance walked using oxygen delivered at 2 l/min by continuous flow or via the PDOD (p = 0.72; CI 0.34 to 1.08). The mean (SD) distance walked on continuous flow oxygen (203.6 (106.1) m) and PDOD (207.9 (109.8) m) was significantly greater than the distance walked with the air cylinder (188.6 (110.02) m); (1.12 fold increase in distance, CI 1.01 to 1.23, p = 0.02, and 1.14 fold increase in distance, CI 1.01 to 1.28, p = 0.03, respectively). CONCLUSIONS: These findings suggest that the pulsed dose oxygen conserving device was as effective as continuous flow oxygen in maintaining arterial oxygen saturation and that the use of this device was associated with similar improvements in exercise tolerance to patients taking continuous flow oxygen therapy.

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