Spirometry in chronic obstructive pulmonary disease.
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Early Diagnosis↗
Biomedical subjects
Peter M A Calverley
Publications and source records attributed to Peter M A Calverley.
The effect of bronchodilators and oxygen alone and in combination on self-paced exercise performance in stable COPD.
Both oxygen therapy and bronchodilators reduce exertional breathlessness and improve exercise tolerance in patients with stable chronic obstructive pulmonary disease (COPD). However their relative effectiveness and the value of their combined use on exercise performance has not been assessed. The effects of 5 mg of salbutamol plus 500 microg ipratropium bromide nebulisation followed by a 6-min walking test while breathing O(2) were studied in a randomised, single-blind, placebo controlled, crossover trial in 28 patients with severe or very severe COPD, breathless on exertion and with oxygen saturation < or = 89% at rest or on exercise. Bronchodilator reversibility was minimal. The 6-min walking distance increased from 356 (128)m to 377 (117)m after the bronchodilator (P<0.05), to 406 (109)m after supplementary oxygen but without bronchodilators (P 0.011 versus bronchodilators/air and 0.001 versus placebo/air), and to 430 (109)m after the combination of oxygen and the bronchodilators (P<0.0001 versus placebo/air and bronchodilators/air; P=0.014 versus placebo/oxygen). End-exercise dyspnea only fell significantly when oxygen and bronchodilator were combined. In severe or very severe COPD patients with relatively fixed airway obstruction bronchodilators enhance exercise performance obtained with oxygen. Clinically relevant improvement is possible when therapies with a different mechanism of action are combined.
Aged↗
Dynamic hyperinflation: is it worth measuring?
A reduced exercise capacity is an important determinant of health status and an independent prognostic marker in patients with chronic obstructive pulmonary disease. The inability to increase expiratory flow at the resting end-expiratory lung volume in the face of expiratory-flow limitation means that end-expiratory lung volume must increase if gas exchange is to be maintained near normal values. This phenomenon is usually referred to as dynamic hyperinflation. The change in operating lung volumes during exercise is related to the intensity of breathlessness. Treatments such as bronchodilators that increase inspiratory capacity or supplemental oxygen, which reduces ventilatory demand, decrease the degree of dynamic hyperinflation at any external workload. However, dynamic hyperinflation is not seen universally in patients with chronic obstructive pulmonary disease as some adopt different breathing patterns when they exercise, or respond to inhaled bronchodilators by changing their pattern of abdominal muscle activation, a behavior that can be counterproductive. Finally, dynamic hyperinflation can be reduced when, for example, breathing oxygen after exercise without changes in dyspnea, as other factors are more important determinants of this symptom in these circumstances. Dynamic hyperinflation can be reliably measured from the inspiratory capacity maneuver in many laboratories. Although knowledge about this variable gives great insight into the mechanisms of therapy, its routine measurement cannot currently be recommended as it does not appear to add additional clinical data beyond those available in present laboratory exercise testing protocols.
Bronchodilator Agents↗
Lung mechanics and dyspnea during exacerbations of chronic obstructive pulmonary disease.
RATIONALE: Exacerbation of chronic obstructive pulmonary disease commonly causes hospitalization. The change in lung mechanics during exacerbation and its relationship to symptoms in spontaneously breathing individuals has not been described. OBJECTIVE: We hypothesized that changes in both airflow and lung volumes would occur during an exacerbation, but that only volume change would relate to symptomatic improvement. METHODS: Lung mechanics and resting dyspnea were recorded in 22 hospitalized patients during recovery from exacerbation. MEASUREMENTS: Spirometry, inspiratory capacity, respiratory system resistance and reactance, tidal breathing patterns, and expiratory flow limitation were recorded after nebulized bronchodilator therapy on the first 3 d after admission, at discharge, and 6 wk postadmission (Day 42). Prebronchodilator measurements were taken on Day 2, at discharge, and on Day 42. MAIN RESULTS: Postbronchodilator inspiratory capacity increased 0.23 +/- 0.07 L by discharge and 0.42 +/- 0.1 L by Day 42, FEV1 rose 0.09 +/- 0.04 and 0.2 +/- 0.05 L at discharge and Day 42, respectively, and FVC increased 0.21 +/- 0.08 and 0.47 +/- 0.09 L at discharge and Day 42 (all p < 0.05). Consistent reduction in dyspnea was seen as the exacerbation resolved. Respiratory system resistance, FEV1/FVC, and expiratory flow limitation were unchanged throughout, indicating that changes in lung volume rather than airflow resistance predominated. CONCLUSIONS: Improvement in operating lung volumes is the principal change seen as a chronic obstructive pulmonary disease exacerbation resolves and increase in inspiratory capacity is a useful guide to a reduction in dyspnea.
Aged↗
Proposal for a multidimensional staging system for chronic obstructive pulmonary disease.
The severity of chronic obstructive pulmonary disease (COPD) is currently assessed using a single physiological measurement, the forced expiratory volume in 1s (FEV1). COPD, however, has complex effects on other aspects of respiratory function, and in many patients is associated with important systemic changes. We hypothesized that a multidimensional staging system for COPD could provide a more complete assessment of the disease's impact. We considered over 40 potential staging variables, evaluating them according to sensitivity to change, measured reproducibly, independence of the information they provide and prognostic value. We finally selected three: FEV1 (including arterial blood gas measurements when FEV1 falls below 35% predicted), Medical Research Council dyspnea scale and body mass index (BMI). Each measure correlates independently with prognosis in COPD, is supported by a significant body of literature and serves as a surrogate for other potentially important variables. We then used principal components analysis (PCA) to determine the degree of association between 30 of the potential variables measured in 813 stable COPD patients. Using PCA, six groups of measurements defined independent categories of patient information: pulmonary function (including FEV1), symptoms of cough and sputum, dyspnea, health status, bronchodilator reversibility and BMI. These include the three principal variables selected for the staging system. Although the staging boundaries were based on existing literature, they have proven useful in predicting survival. We conclude that a multidimensional grading system is useful to assess the impact of COPD.
Age Factors↗
The role of corticosteroids in chronic obstructive pulmonary disease.
Oral corticosteroids are powerful relatively nonspecific antiinflammatory agents with a range of well-characterized side effects. There is good evidence to show that they accelerate the rate of resolution of exacerbations of COPD and relapse is less likely if patients receive these drugs. Maintenance therapy with oral preparations is associated with worse mortality and skeletal muscle myopathy is a particular problem. Corticosteroids have little effect on biopsy proven inflammation or its surrogates in COPD and did not change the rate of decline of FEV (1) over a range of spirometric disease severity in a number of trials each lasting 3 years. However, meta-analysis of the data suggests that a small effect (up to 10 ml /year) might be present. There is more consistent evidence for an effect on postbronchodilator FEV (1) with both fluticasone propionate and budesonide. In patients with a postbronchodilator FEV (1) < 50% predicted where self-reported exacerbations become more common, inhaled corticosteroids can reduce the number of attacks. This effect is the major factor accounting for the reduction in deterioration in health status seen in patients who receive inhaled corticosteroids. Inhaled corticosteroids are much safer than oral therapy, although they do have a predictably higher incidence of candidiasis and hoarseness of the voice. Skin bruising is seen in patients with better lung function who use these drugs. Triamcinolone use is associated with reduction in bone density but this was not seen with budesonide. Combining an inhaled corticosteroid and a long-acting beta-agonist in the same inhaler increases the efficacy of the latte drug in COPD patients, with a significantly larger improvement in FEV (1), a larger reduction in reported breathlessness, and a reduction in exacerbation numbers in those with severe disease where beta-agonists appear to be less effective. Inhaled corticosteroids are not suitable for monotherapy in COPD but can be helpfully combined with an inhaled bronchodilator in patients with symptomatic disease.
Administration, Inhalation↗
Minimal clinically important difference--exacerbations of COPD.
Exacerbations of COPD are now recognised as being important events in the natural history of the condition and become more frequent as the disease worsens. Defining a minimum clinically important difference in exacerbation rate is fraught with difficulty. There is substantial between and within subject differences in the occurrence of these events that makes an individual evaluation of their importance problematic. At present, the most widely used definition of an exacerbation identifies an episode where the patient seeks medical help rather than a predefined change in one or more symptoms. Despite these problems, intervention studies with bronchodilator drugs, inhaled corticosteroids, and pulmonary rehabilitation appear to reduce the frequency of exacerbation events. In patients with an FEV1 below 50% predicted there is reasonable consistency about the magnitude of change and a 4-unit improvement in the St George's Respiratory Questionnaire is commonly associated with a 20-25% reduction in the reported number of exacerbations. Individual studies vary depending upon the recruitment protocol. Patients who experience symptomatic benefit may be those in whom a clinically important change in exacerbations occurs but this concept requires testing prospectively. Existing methodologies for estimating clinically important differences are hard to apply with a binary outcome like this, and more work will be needed to develop a robust approach for dealing with this important clinical variable.
Data Interpretation, Statistical↗
Development of a population-based screening questionnaire for COPD.
COPD is commonly under-diagnosed, in part because people at risk are unaware of the relevant risk factors and do not recognize related symptoms. Providing this information might permit earlier disease identification but the questions chosen should identify those with spirometrically defined airflow obstruction. Using a population-based data set, we have determined which questions identify persons most likely to have airflow obstruction. Potential questions were selected by review of COPD risk factors and clinical features. Validation was by retrospective analysis of the NHANES III data set, a population-based U.S. household survey that included spirometry. We examined the predictive ability of individual questions in a multi-variate framework to correctly discriminate between persons with and without spirometric airway obstruction (defined as FEV1/FVC < 0.70). We then tested the discriminatory ability of the questions in combination. The following items showed significant predictive ability: increased age, smoking status, pack-years, cough, wheeze, and prior diagnosis of asthma or COPD. The best performing combination was age, smoking status, pack-years smoked, wheeze, phlegm, body mass index, and prior diagnosis of obstructive lung disease. Using this combination in a population of current and former smokers aged 40 and over, we achieved a sensitivity of 85% and specificity of 45%, with a positive predictive value of 38% and a negative predictive value of 88%. Performance of this tool is comparable to other screening methods designed for use in a general population. Symptom-based questionnaires can be a viable method to identify persons likely to have COPD in the general population. Dissemination of such tools should raise awareness among at-risk persons and help identify COPD patients in the primary care setting.
Adult↗
The GOLD classification has advanced understanding of COPD.
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Global Health↗
Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome.
AIMS: Obstructive sleep apnoea (OSA) is associated with increased cardiovascular morbidity and mortality. Although it was previously assumed that this was due to its relation with obesity, recent data suggest that OSA is independently associated with the cardiovascular risk factors that comprise metabolic syndrome, including hypertension, insulin resistance, impaired glucose tolerance, and dyslipidaemia. However, as previous studies have only considered these variables individually, it has not been possible to determine the overall association of OSA with this syndrome. METHODS AND RESULTS: We recruited 61 male subjects with OSA and 43 controls. Glucose, insulin, lipids, and blood pressure (BP) were measured following an overnight fast. Insulin resistance was estimated using homeostasis model assessment (HOMA). Metabolic syndrome was diagnosed according to National Cholesterol Education Program (NCEP) criteria. Subjects with OSA were more obese, had higher BP and fasting insulin, were more insulin resistant, had lower HDL cholesterol, and an increased incidence of metabolic syndrome (87% vs. 35%, p<0.0001). In order to determine whether these associations were independent of obesity and other known covariates, a regression analysis adjusted for age, BMI, smoking, and alcohol consumption was performed. This demonstrated that OSA was independently associated with increased systolic and diastolic blood pressure, higher fasting insulin and triglyceride concentrations, decreased HDL cholesterol, increased cholesterol:HDL ratio, and a trend towards higher HOMA values. Metabolic syndrome was 9.1 (95% confidence interval 2.6, 31.2: p<0.0001) times more likely to be present in subjects with OSA. CONCLUSIONS: OSA is independently associated with an increase in the cardiovascular risk factors that comprise the metabolic syndrome and its overall prevalence. This may help explain the increased cardiovascular morbidity and mortality associated with this condition.
Blood Glucose↗
Effect of corticosteroids on exacerbations of asthma and chronic obstructive pulmonary disease.
Periodic exacerbations of disease severity, which may lead to hospitalization, are a characteristic feature of asthma and chronic obstructive pulmonary disease (COPD), becoming more prevalent as disease severity increases. Oral corticosteroids increase the rate of resolution of these episodes in both diseases. Inhaled corticosteroids are much less effective at conventional doses and are not recommended as a primary treatment for exacerbations of either disease. Maintenance therapy with inhaled corticosteroids significantly reduces the chance that a further exacerbation will occur in asthma. In general, increasing doses of inhaled corticosteroids are more effective than placebo therapy in preventing exacerbations, at least until patients become persistently symptomatic and regular users of inhaled corticosteroid therapy. Thereafter, the gains from doubling the dose of inhaled corticosteroid maintenance therapy are modest and generally inferior to those that result from adding other antiinflammatory or bronchodilator agents to the treatment regime. The reduction in the incidence of exacerbations with inhaled corticosteroids, compared with placebo, ranges from 15 to 20% in COPD versus almost 50% in severe asthma. However, given the impact of exacerbations on overall quality of life in COPD, even this modest reduction is likely to be clinically important.
Administration, Inhalation↗
Reducing the frequency and severity of exacerbations of chronic obstructive pulmonary disease.
Exacerbations contribute significantly to impaired health status in chronic obstructive pulmonary disease (COPD), but current therapy can prevent these episodes. Immunization against, for example, influenza offers specific prophylaxis for a minority of episodes. Pulmonary rehabilitation reduces hospital attendance, but its effect wanes. Inhaled bronchodilators such as tiotropium produce similar reductions in exacerbation frequency. Database studies show an association between prescription of inhaled corticosteroids and reduced hospitalization in the older population, a finding confirmed by randomized trials in patients with an FEV(1) of less than 50% predicted. Three 1-year randomized clinical trials studied the effect of combining a long-acting beta-agonist with an inhaled corticosteroids. In these studies, exacerbation frequency was lower with therapy than placebo. Combination therapy had a similar effect to its monocomponents in the trial of inhaled steroids and long-acting beta agonists study using salmeterol and fluticasone. However, when patients with more severe COPD (an FEV(1) of less than 36% predicted) were studied using a combination of budesonide and formoterol, a clear improvement was seen in the overall exacerbation rate compared with the beta-agonist alone. In addition, the time to first exacerbation was increased compared with either drug alone. Health status changes mirrored these effects. In summary, combination therapy can effectively prevent exacerbations in patients with more advanced COPD.
Administration, Inhalation↗
Withdrawal from treatment as an outcome in the ISOLDE study of COPD.
OBJECTIVES: To investigate the determinants of patient withdrawal from our study, and the effect of these withdrawals on the outcome of treatment with inhaled corticosteroids in patients with COPD. DESIGN: A double-blind, placebo-controlled, randomized trial. SETTING: Eighteen outpatient centers in the United Kingdom. PARTICIPANTS: Seven hundred fifty-one patients with stable COPD defined clinically and as baseline postbronchodilator FEV(1) > or = 0.8 L and < 85% predicted, FEV(1)/FVC ratio < 70%, and FEV(1) change after albuterol < 10% of predicted. INTERVENTION: Random assignment of either 500 microg bid of inhaled fluticasone propionate (FP) using a spacer device or an identical placebo inhaler. Treatment was continued for 3 years or until patients withdrew from follow-up. MEASUREMENTS AND RESULTS: Postbronchodilator FEV(1) was measured on three occasions before randomization and every 3 months thereafter. Health status was assessed by the disease-specific St. George Respiratory Questionnaire (SGRQ) and the modified short-form 36 questionnaire (SF-36) at baseline and every 6 months. Three hundred thirty-nine patients withdrew, of whom 156 patients received FP. Prescription of frequent courses of oral prednisolone was the most common reason for withdrawing as specified in the protocol (69 patients in the FP group withdrew due to respiratory symptoms, compared with 93 patients in the placebo group). This explained the significantly greater dropout of placebo-treated patients that was most evident when FEV(1) was < 50% predicted. Patients withdrawing had a significantly more rapid decline in health status, measured by both the SGRQ and the SF-36 (p < 0.001). Those withdrawing from the placebo group had a more rapid decline in FEV(1) and more exacerbations than the FP-treated groups. Baseline FEV(1) was lower in dropouts than in patients completing the study receiving placebo, but there was no difference between the respective groups receiving FP. CONCLUSIONS: Patients who withdrew from follow-up were those with the most rapidly deteriorating health status and lung function. Losing these patients from the final analysis can reduce the power of a study to achieve its primary end point.
Adult↗