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Biomedical subjects

Richard Wood-Baker

Publications and source records attributed to Richard Wood-Baker.

11 recordsLinked to original sources

Nonsmall cell lung carcinoma with neuroendocrine differentiation--an entity of no clinical or prognostic significance.

The existence of non-small cell lung carcinoma with neuroendocrine differentiation as a distinct entity and its relevance for prognostic and treatment purposes is controversial. This study assesses the frequency and biologic and prognostic significance of neuroendocrine (NE) expression of synaptophysin (SNP), chromogranin (Ch), and neural cell adhesion molecule (N-CAM) using tissue microarray (TMA) and immunohistochemistry. Six hundred nine nonsmall cell lung carcinomas (NSCLCs) were reviewed for subclassification. TMA blocks were made using duplicate 0.6-mm-diameter tissue cores and slides stained with SNP, Ch, and N-CAM. Immunoreactivity was considered if 1% or more of tumor cells were positive. Hematoxylin and eosin-stained sections were subclassified as: 243 adenocarcinoma (ACA), 272 squamous cell carcinoma (SCC), 35 large cell carcinoma, 32 non-small cell carcinoma NOS, and 6 other (carcinosarcoma, giant cell carcinoma). Positivity for either marker was identified in 13.6% of NSCLC (76/558). NSCLC showed reactivity for Ch in 0.4% of cases (2/524), for SNP in 7.5% of cases (39/521) and for N-CAM in 8.6% of cases (44/511), whereas only 0.2% of cases (1/517) showed coexpression of SNP and Ch and none of all 3 markers. The assessment of NE differentiation in NSCLC is unnecessary and expensive and is of no clinical or prognostic significance. SNP or N-CAM stains a small minority of NSCLC, whereas Ch immunoreactivity is less common. Positivity for any 2 NE markers is rare. SNP is more likely to be expressed in adenocarcinoma (P=0.01) and N-CAM in squamous-cell carcinoma (P=0.008). Otherwise there was no correlation between immunoreactivity and tumor morphology. Disease specific and overall survival is not influenced by NE differentiation and therefore non-small cell lung carcinoma with neuroendocrine differentiation should not be a subclass distinct from the other NSCLC.

Biomarkers, Tumor↗

Systemic corticosteroids in chronic obstructive pulmonary disease: an overview of Cochrane systematic reviews.

Chronic obstructive pulmonary disease (COPD) is characterized by symptoms of cough, sputum and breathlessness, which become worse during acute exacerbations. The airway inflammation associated with COPD has led to trials of the effect of systemic corticosteroids in COPD assessed in two Cochrane systematic reviews. In stable COPD, compared with placebo, oral corticosteroid treatment increased mean FEV(1) by 53 ml and mean 12-min walking distance by 29 m, but at an increased risk of any drug-related adverse event (OR 7.8). In acute exacerbations, oral corticosteroid treatment decreased the chance of treatment failure (OR 0.48), improved mean FEV(1) at 72 h by 140 ml and improved arterial blood gases, but increased the risk of drug-related adverse events (OR 2.3). Thus, treatment of stable and acute exacerbations of COPD with systemic corticosteroids results in statistically significant average benefits, but at an increased risk of adverse events. In stable COPD, there is little support for the use of systemic corticosteroid treatment, as data on long-term outcomes are lacking. For acute exacerbations, the evidence to support the use of systemic corticosteroids is stronger, but further research is required to define the optimum dose, route and duration.

Administration, Oral↗

Physical activity, spirometry and quality-of-life in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) has a high level of morbidity. There is limited information about levels of physical activity among community dwelling subjects with the disease and its association with lung function and quality of life. In this study, 176 subjects with COPD were recruited from general practices. Physical activity was measured over 7 days using pedometers, quality-of-life using the St. George's Respiratory Questionnaire, and lung function using spirometry, 124 subjects, 60% male, aged 70 +/- 8 years were included in the analysis. Physical activity levels were low, median steps/day for males = 3621, IQR = 4247 and for females = 4287, IQR = 3063. Overall physical activity (median steps/day = 3716, IQR = 3682) was significantly associated with the forced expiratory volume in one second (r = 0.39, p < 0.001) and with St. George's Respiratory Questionnaire score (r = -0.28, p < 0.01). In conclusion, we have demonstrated that in a community-based sample of people with COPD, daily physical activity levels were low compared with usual levels reported for the general population. Physical activity was significantly associated with disease severity, measured by lung function, and quality-of-life.

Aged↗

Stability of the EasyOne ultrasonic spirometer for use in general practice.

OBJECTIVE AND BACKGROUND: Spirometry is recommended for the diagnosis and management of chronic respiratory diseases in the community. Spirometer accuracy is critical, but few general practitioners meet the American Thoracic Society and European Respiratory Society (ATS/ERS) recommendation for daily calibration. The aim of this study was to assess the accuracy and stability of a portable ultrasonic spirometer (EasyOne) that the manufacturer claims does not require regular calibration. METHODS: Six EasyOne spirometers were used in a practice-based spirometry study. Inspiratory and expiratory accuracy was checked periodically using a certified 3-L syringe. Paired calibration checks were performed using a dedicated mouthpiece assembly (spirette) and randomly selected spirettes. RESULTS: The six spirometers were used for up to 26 weeks (mean 23.9 weeks) and a total of 1041 spirometry tests and 75 syringe calibrations were performed. All inspiratory and expiratory calibration checks using a dedicated or randomly selected spirette met the ATS/ERS accuracy criterion (3.00+/-0.105 L). The mean (range) expiratory volume deviation from target volume (3.00 L) was 0.011 L (-0.06-0.09 L) using a dedicated spirette and 0.046 L (-0.09-0.10 L) using randomly selected spirettes. The deviation from target was not affected by the mean flow generated during the calibration procedure. There was no change in calibration during the study. CONCLUSIONS: This study supports the manufacturer's claim that the EasyOne spirometer maintains its calibration during routine clinical use in general practice and does not require daily calibration as specified in international spirometry guidelines.

Equipment Design↗

National survey of spirometer ownership and usage in general practice in Australia.

OBJECTIVES AND BACKGROUND: Despite the lack of data, it is believed that spirometry is underutilized in general practice. The aim of the present study was to determine the availability of spirometry and the level of spirometry training in general practice throughout Australia and compare with international data. METHODS: In total, 5976 general practices throughout Australia were sent a questionnaire requesting details of spirometer ownership, usage and the level and source of spirometry training. To exclude response bias, a follow-up telephone survey was conducted of 160 practices that did not respond to the initial survey. RESULTS: Of practices 19.5% (1125) responded to the initial survey with 64.2% (722) of these owning a spirometer and 83.9% in the follow-up sample. Common reasons for not owning a spirometer were equipment cost (53.3%) and insufficient remuneration (32.8%). Most practices (67.0%) performed one or more tests per week. Practices commonly used spirometry to diagnose (89.5%) and manage (93.9%) asthma, assess breathlessness (83.4%) and to detect and manage other diseases such as COPD (77.7%). Spirometer accuracy was never checked using a syringe 77.8% of practices and 40% did not test a healthy subject as part of their quality assurance programme. Spirometry training was received most commonly through courses run by general practice organizations (38.2%), and the duration of training courses was <2 h in 40% of cases. CONCLUSION: Despite high spirometer ownership in general practice, the frequency of use is low. Low rates of verification of spirometer accuracy and performance suggest the need for reliable, stable spirometers to be available to general practitioners. Regular and more comprehensive training in spirometry is needed.

Australia↗

Written action plans in chronic obstructive pulmonary disease increase appropriate treatment for acute exacerbations.

OBJECTIVE AND BACKGROUND: COPD is a progressive disorder characterized by periodic exacerbations. While comprehensive self-management programmes decrease health-care resource utilization, the essential components are unclear. We performed a study of written action plans in the management of COPD. METHODOLOGY: A randomized, controlled, prospective parallel-group study compared written action plans to usual practice. SUBJECTS: Recruited from general practices, received an educational intervention with or without an action plan, which usually emphasized prompt treatment with antibiotics and corticosteroids. Subjects were followed up 3-monthly for a year. RESULTS: One hundred and thirty-nine participants, mean FEV(1) 45 +/- 16% predicted, were recruited, 81% completing the study. Both groups had a decline in lung function and physical activity, but increase in quality of life over the study period. Exacerbations were common. The intervention group was significantly more likely to have treatment with antibiotics (chi(2) = 3.86; d.f. = 1; P = 0.05) or short course oral corticosteroids (chi(2) = 14.25; d.f. = 1; P < 0.001). No differences were found between the number of general practitioner consultations, attendances at emergency departments or hospitalizations. CONCLUSIONS: The use of a written action plan in COPD increased appropriate therapeutic interventions for exacerbations, but this effect was not associated with a decrease in the use of health-care resources.

Aged↗

Distinguishing asthma and chronic obstructive pulmonary disease: why, why not and how?

WHAT WE NEED TO KNOW: What are the essential differences in the inflammatory process that lead to different pathological outcomes in asthma and chronic obstructive pulmonary disease (COPD)? What factors cause some patients with asthma to have clinical features indistinguishable from COPD, and should these patients be treated differently from those with early-onset, atopic asthma? What should be added to FEV(1) improvement after bronchodilator to enhance the ability of spirometry to distinguish between asthma and COPD? Why is disturbed gas exchange characteristic of stable COPD but rare in asthma? Why and when does COPD become a systemic disease with multiorgan dysfunction, while asthma generally does not? Does the response to bronchodilators in asthma and COPD predict prognosis and response to other interventions? Do people with asthma (airway obstruction, hyper-responsiveness and atopy) and COPD (fixed airflow limitation) have different natural histories, responses to treatment and prognoses? WHAT WE NEED TO DO: Evaluate new diagnostic tools (eg, indirect markers of inflammation) for asthma and COPD. Target older people in epidemiological studies to identify and describe the extent of asthma. Initiate community awareness programs to help older people with dyspnoea recognise they may have symptoms of asthma or COPD that should be assessed by a doctor. Define the clinical and physiological features of asthma and COPD in older people that indicate when and which treatments will achieve maximum benefit with least harm. Develop strategies for better, patient-focused care of people with severe airway disease, concentrating on device use, action plans, side effects, end-of-life decisions, exercise and independence in activities of daily living. Maintain research into new drugs and targets for preventing progressive loss of lung function in asthma and COPD.

Aged↗

Barriers to the use of spirometry in general practice.

BACKGROUND: Guidelines advise chronic obstructive pulmonary disease (COPD) should be diagnosed and managed by using spirometry to demonstrate irreversible airflow limitation and monitor change in smokers and ex-smokers aged over 35 years. METHODS: A cross-sectional study of patients and their general practitioners investigating use of spirometry in COPD in two practices by lung function assessment, review of practice records, interviews and focus groups. RESULTS: Sixteen GPs, and 38 patients with a diagnosis of COPD participated. At diagnosis, although 72% had spirometry, this occurred in only 41% of 17 patients diagnosed by a GP; but in all 19 cases when a specialist was involved. Diagnosis often occurred late, despite all patients having previously recorded symptoms typical of COPD. General practitioners expressed a preference to diagnose COPD on clinical grounds. Although 58% of patients had recent spirometry for current management, only 32% were performed by their GP. There were organisational and technical barriers to spirometry and poor recognition of the essential role of spirometry in the diagnosis of COPD. DISCUSSION: There are a number of potentially reversible factors that hinder practice recommendations regarding the use of spirometry in general practice to diagnose and manage COPD.

Aged↗

Is there a role for systemic corticosteroids in the management of stable chronic obstructive pulmonary disease?

COPD, encompassing both chronic bronchitis and emphysema, usually results from exposure to tobacco smoke. Smoking causes infiltration of the airways with leukocytes, an imbalance between proteases and their naturally occurring inhibitors and local cytokine secretion in the lung, which leads to airway inflammation and alveolar destruction. Corticosteroids have a range of anti-inflammatory actions, particularly inhibition of cytokine secretion, which suggests that they may be effective in COPD. However, data from the highest quality studies available do not show any evidence of significant improvement in symptoms of patients with COPD treated with systemic corticosteroids.A meta-analysis found that about 10% of patients with stable COPD showed an improvement in lung function following treatment with short-term systemic corticosteroids compared with placebo. Exercise capacity in patients with COPD was evaluated in four studies, only one of which found a significant improvement with oral corticosteroids compared with placebo. Long-term systemic corticosteroid treatment in patients with stable COPD has not been found to alter the rate of decline in FEV(1). Although systemic corticosteroids are associated with a range of adverse effects, the data do not allow precise quantification of their contribution to morbidity. However, studies show an increased risk of osteoporosis in COPD. Recent studies have also found an association between oral corticosteroid administration and mortality in patients with stable COPD, but it is not clear if this is a cause and effect relationship. Current data do not support long-term administration of systemic corticosteroids to all patients with stable COPD. Results of studies suggest that short-term oral corticosteroid administration may identify a sub-population of patients with COPD who may benefit through a reduction in the decline in FEV(1) and better control of symptoms by long-term administration of inhaled corticosteroids; these findings need to be tested by further research.

Administration, Inhalation↗

Exercise-induced oxyhaemoglobin desaturation, ventilatory limitation and lung diffusing capacity in women during and after exercise.

Arterial haemoglobin saturation during exercise in healthy young women [eight subjects mean (SEM) age 20.8 (1.8) years] was measured to confirm the theory that young women experience exercise-induced arterial hypoxaemia (EIAH) at a lower relative percentage of maximal oxygen uptake (VO(2max)) than has been documented in their male counterparts. To determine if flow limitation [the percentage of the tidal volume ( V(T)) that met or exceeded the boundary established by multiple maximal expiratory manoeuvres] and/or post-exercise lung diffusing capacity are linked to EIAH in women, and to investigate the influence of exercise intensity and duration on post-exercise carbon monoxide lung diffusing capacity ( D(L, CO)), these parameters were measured during and after three exercise tests (incremental test until exhaustion, 5 km run and 5 km run with sprint). All subjects experienced physiologically significant EIAH (a fall of more than 3% in oxygen saturation of arterial blood from levels at rest) and seven subjects experienced flow limitation during the VO(2max) protocol [mean (SD) 12.2 (8.8)% of V(T)]. Even though there was no significant relationship between aerobic capacity and the degree of flow limitation ( r=0.33, P>0.05), the flow limitation was related to absolute ventilation in the subjects studied ( r=0.82, P<0.05). There was no significant relationship between decrements in post exercise D(L, CO) and EIAH ( r=0.05, P>0.05), however there was a strong correlation between the extent of flow limitation (% of V(T)) and EIAH ( r=0.71). Significant decreases in D(L, CO) lasted for up to 16 h after each of the exercise tests ( P<0.05) and lasted for a further 8 h after the maximal test ( P<0.05). Exercise intensity was the main contributing factor to the observed decreases in post-exercise D(L, CO) with the percentage of VO(2max) attained during the various tests being significantly related to the fall in D(L, CO) for 1, 2, 3, 16 and 24 h after exercise ( P<0.05). As the appearance of flow limitation closely coincided with the appearance of EIAH, the results from the present study suggest that flow limitation is a contributing factor to EIAH in women although the exact mechanism remains unclear.

Adult↗