S L Hill

Physiological and radiological characterisation of patients diagnosed with chronic obstructive pulmonary disease in primary care

BACKGROUND Chronic obstructive pulmonary disease (COPD) is common although often poorly characterised, particularly in primary care. However, application of guidelines to the management of such patients needs a clear understanding of the phenotype. In particular, the British guidelines for the management of COPD recommend that the diagnosis is based on appropriate symptoms and evidence of airflow obstruction as determined by a forced expiratory volume in one second (FEV1) of <80% of the predicted value and an FEV1/VC ratio of <70%. METHODS A study was undertaken of 110 patients aged 40–80 years who had presented to their general practitioner with an acute exacerbation of COPD. The episode was treated at home and, when patients had recovered to the stable state (two months later), they were characterised by full lung function tests and a high resolution computed tomographic (HRCT) scan of the chest. RESULTS There was a wide range of impairment of FEV1 which was in the normal range (⩾80%) in 30%, mildly impaired (60–79%) in 18%, moderately impaired (40–59%) in 33%, and severely impaired (<40%) in 19% of patients. A reduced FEV1/VC ratio was present in all patients with an FEV1 of <80% predicted but also in 41% of those with an FEV1 of ⩾80% predicted. Only 5% of patients had a substantial bronchodilator response suggesting a diagnosis of asthma. Emphysema was present in 51% of patients and confined to the upper lobes in most (73% of these patients). HRCT evidence of bronchiectasis was noted in 29% of patients and was predominantly tubular; most (81%) were current or ex-smokers. A solitary pulmonary nodule was seen on 9% of scans and unsuspected lung malignancy was diagnosed in two patients. CONCLUSIONS This study confirms that COPD in primary care is a heterogeneous condition. Some patients do not fulfil the proposed diagnostic criteria with FEV1 of ⩾80% predicted but they may nevertheless have airflow obstruction. Bronchiectasis is common in this group of patients, as is unsuspected malignancy. These findings should be considered when developing recommendations for the investigation and management of COPD in the community.

Relationship between airway inflammation and the frequency of exacerbations in patients with smoking related COPD

BACKGROUND Patients with more frequent exacerbations of chronic obstructive pulmonary disease (COPD) may have increased bronchial inflammation. Airway inflammation was measured in patients who had been thoroughly investigated with full pulmonary function testing, thoracic HRCT scanning, and sputum microbiology to examine further the relationship between exacerbation frequency and bronchial inflammation. METHODS Airway inflammation (spontaneous sputum sol phase myeloperoxidase (MPO), elastase, leukotriene (LT)B4, interleukin (IL)-8, secretory leukoprotenase inhibitor (SLPI), protein leakage) and serum levels of C reactive protein (CRP) were compared in 40 patients with stable, smoking related COPD, divided into those with frequent (⩾3/year) or infrequent (⩽2/year) exacerbations according to the number of primary care consultations during the preceding year. The comparisons were repeated after excluding eight otherwise clinically indistinguishable patients who had tubular bronchiectasis on the HRCT scan. RESULTS Patients with frequent (n=12) and infrequent (n=28) exacerbations were indistinguishable in terms of their clinical, pulmonary function, and sputum characteristics, CRP concentrations, and all of their bronchial inflammatory parameters (p>0.05). The patients without evidence of tubular bronchiectasis (n=32) were equally well matched but the sputum concentrations of SLPI were significantly lower in the frequent exacerbators (n=8) in this subset analysis (p<0.05). CONCLUSIONS There are several clinical features that directly influence bronchial inflammation in COPD. When these were carefully controlled for, patients with more frequent reported exacerbations had lower sputum concentrations of SLPI. This important antiproteinase is also known to possess antibacterial and antiviral activity. Further studies are required into the nature of recurrent exacerbations and, in particular, the regulation and role of SLPI in affected individuals.

Exercise training and inspiratory muscle training in patients with bronchiectasis

Background: Bronchiectasis is a chronic suppurative lung disease often characterised by airflow obstruction and hyperinflation, and leading to decreased exercise tolerance and reduced health status. The role of pulmonary rehabilitation (PR) and inspiratory muscle training (IMT) has not been investigated in this group of patients. Methods: Thirty two patients with idiopathic bronchiectasis were randomly allocated to one of three groups: PR plus sham IMT (PR-SHAM), PR plus targeted IMT (PR-IMT), or control. All patients (except the control group) underwent an 8 week training programme of either PR or PR plus targeted IMT. Exercise training during PR was performed three times weekly at 80% of the peak heart rate. IMT was performed at home for 15 minutes twice daily over the 8 week period. Results: PR-SHAM and PR-IMT resulted in significant increases in the incremental shuttle walking test of 96.7 metres (95% confidence interval (CI) 59.6 to 133.7) and 124.5 metres (95% CI 63.2 to 185.9), respectively, and in endurance exercise capacity of 174.9% (95% CI 34.7 to 426.1) and 205.7% (95% CI 31.6 to 310.6). There were no statistically significant differences in the improvements in exercise between the two groups. Significant improvements in inspiratory muscle strength were also observed both in the PR-IMT group (21.4 cm H2O increase, 95% CI 9.3 to 33.4; p = 0.008) and the PR-SHAM group (12.0 cm H2O increase, 95% CI 1.1 to 22.9; p = 0.04), the magnitude of which were also similar (p = 0.220). Improvements in exercise capacity were maintained in the PR-IMT group 3 months after training, but not in the PR-SHAM group. Conclusion: PR is effective in improving exercise tolerance in bronchiectasis but there is no additional advantage of simultaneous IMT. IMT may, however, be important in the longevity of the training effects.

Assessment of airway neutrophils by sputum colour: correlation with airways inflammation

BACKGROUND Airway inflammation, with recruitment of neutrophils to the airway lumen, results in purulent secretions and a variety of potential adverse consequences for patients with chronic bronchitis and bronchiectasis. We hypothesised that gradations of sputum colour would correlate directly with the myeloperoxidase content of sputum and with various other indicators of the activity and consequences of bronchial diseases. METHODS To test this hypothesis, we quantified sputum colour by reference to a sensitive nine point colour chart and correlated this assessment with indices of a number of inflammatory mediators in sputum. RESULTS The results indicate that standardised visual measurements of sputum colour correlated strongly with myeloperoxidase, interleukin 8, leucocyte elastase (both activity and total quantity), sputum volume, protein leak, and secretory leucocyte proteinase inhibitor (p<0.001 for all). In addition, there was a strong direct correlation between leucocyte elastase and both myeloperoxidase (p<0.003) and sputum volume (p<0.001), but a strong negative correlation with secretory leucocyte proteinase inhibitor (p<0.001). CONCLUSIONS These results indicate that sputum colour graded visually relates to the activity of the underlying markers of bronchial inflammation. The results of this simple visual analysis of sputum provides guidance concerning underlying inflammation and its damaging potential. It also provides a useful scientific tool for improving the monitoring of chronic airways diseases and response to treatment.

Short term response of patients with bronchiectasis to treatment with amoxycillin given in standard or high doses orally or by inhalation.

The effect of three amoxycillin treatment regimens on purulent secretions of patients with bronchiectasis has been studied. On the basis of information recorded on a diary card the patients were divided into three groups, according to the usual nature of their secretions: seven who produced mucoid sputum, which occasionally became purulent; seven whose secretions were usually mucopurulent but occasionally purulent; and 19 whose secretions were persistently purulent. Treatment with capsules of amoxycillin in a dosage of 250 mg three times a day resulted in clearance of purulent secretions in patients of the mucoid group when they were treated for a clinical exacerbation. The sputum remained clear in these patients for long periods before a further exacerbation (median 6 1/2, range 1-11 months). The mucopurulent-purulent group also responded to this dosage but sputum purulence returned more rapidly (median 9, range 4-31 days). Only three of the 19 (17%) patients with persistently purulent secretions showed a macroscopic response to this dosage, whereas seven (60%) of 12 patients who received the higher dosage (3 g sachets twice a day) responded. Among the failures, some responded to nebulised amoxycillin, suggesting that higher levels of amoxycillin in secretions are required in these patients. Macroscopic clearance of purulent secretions was finally achieved in most of the patients studied. The response was not always predictable from the results of sputum culture. Clearance of secretions by antibiotics was also identified by the patients, using a diary card score. Improvements in well being and in symptoms were noticed even in the group who usually produced mucopurulent and purulent secretions even though they appeared to be clinically stable before treatment.

IgG subclasses in the serum and sputum from patients with bronchiectasis

BACKGROUND IgG subclass deficiency is often associated with recurrent pulmonary infections. The prevalence of deficiency in a large well characterised group of patients with bronchiectasis has not previously been established. METHODS Serum IgG subclass concentrations in 89 patients with bronchiectasis were compared with those obtained from a group of 82 age and sex matched normal healthy controls. Sputum IgG subclass concentrations were also assessed in 44 of the patients. Albumin was measured as a marker of protein transudation from plasma to determine the degree of local IgG subclass production. RESULTS The serum concentrations of IgG1, IgG2 and IgG3 were increased in the patients compared with the control group whereas IgG4 concentrations were not. There was an overall incidence of deficiency of 1% for subclasses 1–3 and 5% for subclass 4 in patients with bronchiectasis based on observed concentrations being below the lower limit of the control group range. The concentrations of IgG subclasses in sputum were partly dependent upon the degree of inflammation as assessed by the macroscopic appearance of purulence. A comparison of the ratio of sputum:serum subclass concentration and sputum:serum albumin, however, revealed that all of the subclasses were present at greater concentrations than could be accounted for by transudation alone. CONCLUSIONS A new normal control range for serum IgG subclasses has been established and from this range it was found that IgG subclass deficiency in a group of unselected patients with bronchiectasis was comparatively rare. A significant degree of local IgG production was also suggested in the lungs of these patients.

Effect of fluticasone propionate on neutrophil chemotaxis, superoxide generation, and extracellular proteolytic activity in vitro.

BACKGROUND--Corticosteroids are widely used in the treatment of many inflammatory conditions but the exact mode of action on neutrophil function is uncertain. Fluticasone propionate is a new topically active synthetic steroid which can be measured in body fluids and which undergoes first pass metabolism. METHODS--The effects of fluticasone propionate on the function of neutrophils isolated from normal, healthy control subjects and on the chemotactic activity of sputum sol phase were assessed. RESULTS--Preincubation of neutrophils with fluticasone propionate reduced the chemotactic response to 10(-8) mol/l F-Met-Leu-Phe (FMLP) and to a 1:5 dilution of sputum sol phase in a dose dependent manner. Furthermore, when fluticasone propionate was added to sputum from eight patients with stable chronic obstructive bronchitis the chemotactic activity of a 1:5 dilution of the sol phase fell from a mean (SE) value of 22.2 (1.21) cells/field to 19.6 (0.89), 17.1 (0.74), and 11.9 (0.6) cells field at 1 mumol/l, 10 mumol/l, and 100 mumol/l, respectively. In further experiments fluticasone propionate preincubated with neutrophils inhibited fibronectin degradation by resting cells and by cells stimulated by FMLP (15.2% inhibition of resting cells, 5.1% inhibition of stimulated cells with 1 mumol/l fluticasone propionate, 24% and 18.7% inhibition respectively at 100 mumol/l fluticasone propionate. Fluticasone propionate had no effect on generation of superoxide anion by resting or stimulated cells. CONCLUSIONS--These results indicate that fluticasone propionate has a direct suppressive effect on several aspects of neutrophil function and may suggest a role for this agent in the modulation of neutrophil mediated damage to connective tissue.

Effect of storage and postage on recovery and quantitation of bacteria in sputum samples

Aims: The aims of the study were to compare bacterial recovery following storage of sputum samples at 20°C room temperature and 4°C (refrigerated) for 24 h, and to determine the effect of postage on viable bacterial numbers. Methods: A total of 38 individual sputum samples from clinically stable patients with bronchiectasis were split into three equal aliquots and quantitative bacterial culture was performed (i) immediately, (ii) following storage at 4°C for 24 h or (iii) following storage at 20°C for 24 h. A further 42 sputum samples were split into two equal aliquots and quantitative bacterial culture was performed either immediately or following postage back to the laboratory by first-class mail from an outside location. Results: The predominant organism could still be recovered following storage at 4°C and 20°C, but viable numbers were significantly reduced following storage at 4°C (p<0.004) by at least an order of magnitude (10-fold) in 24% of samples stored at 4°C compared with only 8% stored at 20°C. Posting samples back to the laboratory did not affect the recovery of bacterial species and there was no difference in viable numbers isolated. Conclusions: The results suggest that storage at room temperature is preferable to refrigeration as it retains the species isolated and the viable number. The data also confirm that sputum samples can be posted to the laboratory from patients in the community without affecting qualitative or quantitative results.

Exacerbations of COPD Diagnosed in Primary Care: Changes in Spirometry and Relationship to Symptoms

The study objective was to assess spirometric changes during resolution of acute exacerbations of COPD diagnosed and treated in primary care and their relationship to clinical features. Spirometry was carried out on 101 patients with AECOPD presenting to a primary care physician on the day of presentation, days 5, 10–14, 28, and 56 after presentation and traces were analyzed including quality and reproducibility. Eighty-three patients produced at least one technically acceptable spirometer trace at presentation and 60 patients produced acceptable traces at all time points. The increase in FEV1 and VC occurred during the first 5 days after presentation, with a median increase in postbronchodilator FEV1 of 55 ml (IQR, −63 to 128, p = 0.003) and VC of 90 ml (IQR −78 to 308 ml, p < 0.001). The improvement in prebronchodilator values related to the bronchodilator reversibility at presentation and was strongest for VC (by day 28: r = 0.522, p < 0.001). Patients presenting with purulent sputum demonstrated improvements in FEV1 and VC but this was limited to FEV1 in those with mucoid sputum. The initial dyspnoea score related to the changes in spirometry. It is possible to obtain clinically useful spirometric traces in most patients presenting with an acute exacerbation in primary care. Some patients present with changes in sputum characteristics and cough without increased breathlessness. However, exacerbations characterized by increased breathlessness are associated with increases in airflow obstruction that may be influenced by sputum characteristics and/or changes in airway reactivity.

Joint protection and hand exercises for hand osteoarthritis: an economic evaluation comparing methods for the analysis of factorial trials

Objectives. Evidence regarding the cost-effectiveness of joint protection and hand exercises for the management of hand OA is not well established. The primary aim of this study is to assess the cost-effectiveness (cost-utility) of these management options. In addition, given the absence of consensus regarding the conduct of economic evaluation alongside factorial trials, we compare different analytical methodologies. Methods. A trial-based economic evaluation to assess the cost-utility of joint protection only, hand exercises only and joint protection plus hand exercises compared with leaflet and advice was undertaken over a 12 month period from a UK National Health Service perspective. Patient-level mean costs and mean quality-adjusted life years (QALYs) were calculated for each trial arm. Incremental cost-effectiveness ratios (ICERs) were estimated and cost-effectiveness acceptability curves were constructed. The base case analysis used a within-the-table analysis methodology. Two further methods were explored: the at-the-margins approach and a regression-based approach with or without an interaction term. Results. Mean costs (QALYs) were £58.46 (s.d. 0.662) for leaflet and advice, £92.12 (s.d. 0.659) for joint protection, £64.51 (s.d. 0.681) for hand exercises and £112.38 (s.d. 0.658) for joint protection plus hand exercises. In the base case, hand exercises were the cost-effective option, with an ICER of £318 per QALY gained. Hand exercises remained the most cost-effective management strategy when adopting alternative methodological approaches. Conclusion. This is the first trial evaluating the cost-effectiveness of occupational therapy-supported approaches to self-management for hand OA. Our findings showed that hand exercises were the most cost-effective option.