Chronic Obstructive Pulmonary Disease Function Research Articles

Effects of polycythemia on systemic endothelial function in chronic hypoxic lung disease

Chronic obstructive pulmonary disease (COPD) is a major risk factor for cardiovascular disease. Polycythemia, a common complication of hypoxic COPD, may affect systemic vascular function by altering blood viscosity, vessel wall shear stress (WSS), and endothelium-derived nitric oxide (NO) release. Here, we evaluated the effects of hypoxia-related polycythemia on systemic endothelial function in patients with COPD. We investigated blood viscosity, WSS, and endothelial function in 15 polycythemic and 13 normocythemic patients with COPD of equal severity, by recording brachial artery diameter variations in response to hyperemia and by using venous occlusion plethysmography (VOP) to measure forearm blood flow (FBF) responses to a brachial artery infusion of acetylcholine (ACh), bradykinin (BK), sodium nitroprusside (SNP), substance P (SP), isoptin, and N-monomethyl-L-arginine (L-NMMA). At baseline, polycythemic patients had higher blood viscosity and larger brachial artery diameter than normocythemic patients but similar calculated WSS. Flow-mediated brachial artery vasodilation was increased in the polycythemic patients, in proportion to the hemoglobin levels. ACh-induced vasodilation was markedly impaired in the polycythemic patients and negatively correlated with hemoglobin levels. FBF responses to endothelium- (BK, SP) and non-endothelium-dependent (SNP, isoptin) vasodilators were not significantly different between the two groups. L-NMMA infusion induced a similar vasoconstrictor response in both groups, in accordance with their similar baseline WSS. In conclusion, systemic arteries in polycythemic patients adjust appropriately to chronic or acute WSS elevations by appropriate basal and stimulated NO release. Overall, our results suggest that moderate polycythemia has no adverse effect on vascular function in COPD.

Cigarette Smoke-Induced Changes to Alveolar Macrophage Phenotype and Function Are Improved by Treatment with Procysteine

Defective efferocytosis may perpetuate inflammation in smokers with or without chronic obstructive pulmonary disease (COPD). Macrophages may phenotypically polarize to classically activated M1 (proinflammatory; regulation of antigen presentation) or alternatively activated M2 (poor antigen presentation; improved efferocytosis) markers. In bronchoalveolar lavage (BAL)-derived macrophages from control subjects and smoker/ex-smoker COPD subjects, we investigated M1 markers (antigen-presenting major histocompatibility complex [MHC] Classes I and II), complement receptors (CRs), the high-affinity Fc receptor involved with immunoglobulin binding for phagocytosis (Fc-gamma receptor, FcγR1), M2 markers (dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin [DC-SIGN] and arginase), and macrophage function (efferocytosis and proinflammatory cytokine production in response to LPS). The availability of glutathione (GSH) in BAL was assessed, because GSH is essential for both M1 function and efferocytosis. We used a murine model to investigate macrophage phenotype/function further in response to cigarette smoke. In lung tissue (disaggregated) and BAL, we investigated CRs, the available GSH, arginase, and efferocytosis. We further investigated the therapeutic effects of an oral administration of a GSH precursor, cysteine l-2-oxothiazolidine-4-carboxylic acid (procysteine). Significantly decreased efferocytosis, available GSH, and M1 antigen-presenting molecules were evident in both COPD groups, with increased DC-SIGN and production of proinflammatory cytokines. Increased CR-3 was evident in the current-smoker COPD group. In smoke-exposed mice, we found decreased efferocytosis (BAL and tissue) and available GSH, and increased arginase, CR-3, and CR-4. Treatment with procysteine significantly increased GSH, efferocytosis (BAL: control group, 26.2%; smoke-exposed group, 17.66%; procysteine + smoke-exposed group, 27.8%; tissue: control group, 35.9%; smoke-exposed group, 21.6%; procysteine + smoke-exposed group, 34.5%), and decreased CR-4 in lung tissue. Macrophages in COPD are of a mixed phenotype and function. The increased efferocytosis and availability of GSH in response to procysteine indicates that this treatment may be useful as adjunct therapy for improving macrophage function in COPD and in susceptible smokers.

Global muscle dysfunction as a risk factor of readmission to hospital due to COPD exacerbations

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with several modifiable (sedentary life-style, smoking, malnutrition, hypoxemia) and non-modifiable (age, co-morbidities, severity of pulmonary function, respiratory infections) risk factors. We hypothesise that most of these risk factors may have a converging and deleterious effects on both respiratory and peripheral muscle function in COPD patients. A multicentre study was carried out in 121 COPD patients (92% males, 63±11 yr, FEV(1), 49±17%pred). Assessments included anthropometrics, lung function, body composition using bioelectrical impedance analysis (BIA), and global muscle function (peripheral muscle (dominant and non-dominant hand grip strength, HGS), inspiratory (PI(max)), and expiratory (PE(max)) muscle strength). GOLD stage, clinical status (stable vs. non-stable) and both current and past hospital admissions due to COPD exacerbations were included as covariates in the analyses. Respiratory and peripheral muscle weakness were observed in all subsets of patients. Muscle weakness, was significantly associated with both current and past hospitalisations. Patients with history of multiple admissions showed increased global muscle weakness after adjusting by FEV(1) (PE(max), OR=6.8, p<0.01; PI(max), OR=2.9, p<0.05; HGSd, OR=2.4, and HGSnd, OR=2.6, p=0.05). Moreover, a significant increase in both respiratory and peripheral muscle weakness, after adjusting by FEV(1), was associated with current acute exacerbations. Muscle dysfunction, adjusted by GOLD stage, is associated with an increased risk of hospital admissions due to acute episodes of exacerbation of the disease. Current exacerbations further deteriorate muscle dysfunction.

1H Nuclear Magnetic Resonance Metabolomics Analysis Identifies Novel Urinary Biomarkers for Lung Function

Chronic obstructive pulmonary disease (COPD), characterized by chronic airflow limitation, is a serious public health concern. In this study, we used proton nuclear magnetic resonance ((1)H NMR) spectroscopy to identify and quantify metabolites associated with lung function in COPD. Plasma and urine were collected from 197 adults with COPD and from 195 without COPD. Samples were assayed using a 600 MHz NMR spectrometer, and the resulting spectra were analyzed against quantitative spirometric measures of lung function. After correcting for false discoveries and adjusting for covariates (sex, age, smoking) several spectral regions in urine were found to be significantly associated with baseline lung function. These regions correspond to the metabolites trigonelline, hippurate and formate. Concentrations of each metabolite, standardized to urinary creatinine, were associated with baseline lung function (minimum p-value = 0.0002 for trigonelline). No significant associations were found with plasma metabolites. Urinary hippurate and formate are often related to gut microflora. This could suggest that the microbiome varies between individuals with different lung function. Alternatively, the associated metabolites may reflect lifestyle differences affecting overall health. Our results will require replication and validation, but demonstrate the utility of NMR metabolomics as a screening tool for identifying novel biomarkers of pulmonary outcomes.

Influencing the decline of lung function in COPD: use of pharmacotherapy

Chronic obstructive pulmonary disease (COPD) is a common and deadly disease. One of the hallmarks of COPD is an accelerated decline in lung function, as measured by spirometry. Inflammation, oxidative stress and other pathways are hypothesized to be important in this deterioration. Because progressive airflow obstruction is associated with considerable morbidity and mortality, a major goal of COPD treatment has been to slow or prevent the accelerated decline in lung function. Until recently, the only known effective intervention was smoking cessation. However, newly reported large clinical trials have shown that commonly used medications may help slow the rate of lung function decline. The effect of these medications is modest (and thus required such large, expensive trials) and to be of clinical benefit, therapy would likely need to start early in the course of disease and be prolonged. Such a treatment strategy aimed at preservation of lung function would need to be balanced against the side effects and costs of prolonged therapy. A variety of newer classes of medications may help target other pathophysiologically important pathways, and could be used in the future to prevent lung function decline in COPD.

Impact of dietary shift to higher-antioxidant foods in COPD: a randomised trial

Chronic obstructive pulmonary disease (COPD) is characterised by increased oxidative stress. Dietary factors, such as ample consumption of foods rich in antioxidants, such as fruit and vegetables, might have beneficial effects in COPD patients. The association between dietary shift to foods rich in antioxidants and lung function in COPD was investigated in a 3-yr prospective study. A total of 120 COPD patients were randomised to follow either a diet based on increased consumption of fresh fruit and vegetables (intervention group (IG)) or a free diet (control group (CG)). The mean consumption of foods containing antioxidants was higher in the IG than in the CG throughout the study period (p<0.05). The relationship between consumption of foods rich in antioxidants and percentage predicted forced expiratory volume in 1 s was assessed using a general linear model for repeated measures; the two groups overall were different in time (p = 0.03), with the IG showing a better outcome. In investigating the effect of several confounders (sex, age, smoking status, comorbid conditions and exacerbation) of group response over time, nonsignificant interactions were found between confounders, group and time. These findings suggest that a dietary shift to higher-antioxidant food intake may be associated with improvement in lung function, and, in this respect, dietary interventions might be considered in COPD management.

Inhaled corticosteroids in chronic obstructive pulmonary disease: a review

Importance of the field: Chronic obstructive pulmonary disease (COPD) is a disease characterized by chronic airflow obstruction and a progressive lung function decline. Although widely used, the efficacy of inhaled corticosteroids (ICS) in the treatment of COPD remains a matter of debate.Areas covered in this review: This article reviews the evidence about the effects of inhaled corticosteroids in the treatment of COPD.What the reader will gain: Short-term treatment with ICS improves lung function and quality of life; in addition, several studies with longer follow-up have shown less decline over time in quality of life, and fewer exacerbations. By contrast, long-term studies have been unable to show substantial improvement in the decline of lung function in COPD. Based on these findings, it was concluded that the use of ICS did not influence the natural course of COPD. However, this conclusion has been challenged by two subsequent studies, TORCH and GLUCOLD, which both showed a reduction in lung-function decline over time with the use of ICS. These two studies indicate that ICS might indeed influence the natural course of the disease, at least in a subgroup of COPD patients.Take home message: Further studies are needed to identify which individuals have a favorable short- and long-term response to ICS treatment.

Effect of Fluticasone With and Without Salmeterol on Pulmonary Outcomes in Chronic Obstructive Pulmonary Disease

Inhaled corticosteroids (ICSs) and long-acting beta(2)-agonists (LABAs) are used to treat moderate to severe chronic obstructive pulmonary disease (COPD). To determine whether long-term ICS therapy, with and without LABAs, reduces inflammation and improves pulmonary function in COPD. Randomized, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00158847) 2 university medical centers in The Netherlands. 114 steroid-naive current or former smokers with moderate to severe COPD. Cell counts in bronchial biopsies and sputum (primary outcome); methacholine responsiveness at baseline, 6, and 30 months; and clinical outcomes every 3 months. Random assignment by minimization method to receive fluticasone propionate, 500 microg twice daily, for 6 months (n = 31) or 30 months (n = 26); fluticasone, 500 microg twice daily, and salmeterol, 50 microg twice daily, for 30 months (single inhaler; n = 28); or placebo twice daily (n = 29). 101 patients were greater than 70% adherent to therapy. Fluticasone therapy decreased counts of mucosal CD3(+) cells (-55% [95% CI, -74% to -22%]; P = 0.004), CD4(+) cells (-78% [CI, -88% to 60%]; P < 0.001), CD8(+) cells (-57% [CI, -77% to -18%]; P = 0.010), and mast cells (-38% [CI, -60% to -2%]; P = 0.039) and reduced hyperresponsiveness (P = 0.036) versus placebo at 6 months, with effects maintained after 30 months. Fluticasone therapy for 30 months reduced mast cell count and increased eosinophil count and percentage of intact epithelium, with accompanying reductions in sputum neutrophil, macrophage, and lymphocyte counts and improvements in FEV(1) decline, dyspnea, and quality of life. Reductions in inflammatory cells correlated with clinical improvements. Discontinuing fluticasone therapy at 6 months increased counts of CD3(+) cells (120% [CI, 24% to 289%]; P = 0.007), mast cells (218% [CI, 99% to 407%]; P < 0.001), and plasma cells (118% [CI, 9% to 336%]; P = 0.028) and worsened clinical outcome. Adding salmeterol improved FEV(1) level. The study was not designed to evaluate clinical outcomes. Measurement of primary outcome was not available for 24% of patients at 30 months. ICS therapy decreases inflammation and can attenuate decline in lung function in steroid-naive patients with moderate to severe COPD. Adding LABAs does not enhance these effects. .

Novel strategy to identify genetic risk factors for COPD severity: a genetic isolate

Studies using genetic isolates with limited genetic variation may be useful in chronic obstructive pulmonary disease (COPD) genetics, but are thus far lacking. The associations between single nucleotide polymorphisms (SNPs) in candidate genes and lung function in COPD were studied in a genetic isolate. In 91 subjects with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage >or=1 COPD, who were members of an extended pedigree including 6,175 people from the Genetic Research in Isolated Populations study, 32 SNPs were analysed in 13 candidate genes: a disintegrin and metalloprotease domain 33 gene (ADAM33), transforming growth factor-beta1 gene ( TGFB1), matrix metalloprotease-1 gene (MMP1), MMP2, MMP9, MMP12, tissue inhibitor of metalloprotease-1 gene (TIMP1), surfactant protein A1 gene (SFTPA1 ), SFTPA2, SFTPB, SFTPD, glutathione S-transferase P1 gene (GSTP1), and haem oxygenase 1 gene ( HMOX1). Their relation to forced expiratory volume in 1 s (FEV( 1)), inspiratory vital capacity (IVC) and FEV(1)/IVC were studied using restricted maximum likelihood linear mixed modelling, accounting for pedigree structure. Significant associations were replicated in the general Vlagtwedde/Vlaardingen study. Six SNPs in TGFB1, SFTPA1, SFTPA2 and SFTPD were significantly associated with FEV(1)/IVC in subjects with GOLD stage >or=1 COPD. Two SNPs in TGFB1 (C to T substitution at nucleotide -509 and substitution of leucine 10 with proline (Leu10Pro)), Leu50Val in SFTPA1 and Ala160Thr in SFTPD showed evidence suggestive of association with FEV(1)/IVC in subjects with GOLD stage >or=2 COPD. The TGFB1 associations were replicated in GOLD stage >or=2 patients from the Vlagtwedde/Vlaardingen population, with similar effect sizes. It was shown that a genetic isolate can be used to determine the genetics of lung function, which can be replicated in COPD patients from an independent population.

Overcoming steroid unresponsiveness in airways disease

Most of the patients with asthma are found to be successfully treated with conventional therapy. However, there are a small proportion of asthmatic patients who fail to respond to corticosteroids even at high doses or with supplementary therapy. In addition, even high doses of corticosteroids have a minimal effect on the inexorable decline in lung function in COPD (chronic obstructive pulmonary disease) and only a small effect in reducing exacerbations. Corticosteroid-insensitivity therefore presents a profound management problem. Corticosteroids act through a cytosolic receptor [GR (glucocorticoid receptor)], which is activated and translocates to the nucleus. Once in the nucleus, it either binds to DNA and switches on the expression of anti-inflammatory genes or represses the activity of distinct signalling pathways such as NF-kappaB (nuclear factor kappaB), AP-1 (activator protein-1) or MAPKs (mitogen-activated protein kinases). This latter step requires the recruitment of co-repressor molecules. A failure to respond to corticosteroids may therefore result from lack of binding to GR, reduced GR expression, lack of co-repressor activity or enhanced activation of inflammatory pathways. These events can be modulated by oxidative stress or high levels of inflammatory cytokines, which may lead to a reduced clinical outcome. Understanding the molecular mechanisms of GR action, and inaction, may lead to the development of new anti-inflammatory drugs or reverse the relative corticosteroid-insensitivity that is characteristic of these diseases.

Structure and Function in COPD

The recent definition that chronic obstructive pulmonary disease (COPD) is a “preventable and treatable disease state characterized by airflow limitation that is not fully reversible” reminds that the respiratory functional evaluation is an integral part in the diagnostic and follow-up process in this disease. This review has the scope to focus on some of the most debated pathophysiological and functional issues. One of these is how airflow obstruction occurs and progresses. To this aim, we will discuss the functional role of mucus, increased thickness of the submucosa and adventitia, airway smooth muscle, site of airway narrowing, collapsibility of the central airways, and loss of lung elastic recoil in decreasing flow. Then, we will present a functional clinical approach to the disease that covers the most important features of the disease, such as diagnosis, follow-up, severity assessment, lung hyperinflation, and bronchodilator response. Keywords: Airflow limitation, airway narrowing, lung elastic recoil, lung hyperinflation, bronchodilation, pathology, lung function tests

Neural respiratory drive in healthy subjects and in COPD

The aim of the present study was to use the diaphragm electromyogram (EMG(di)) to compare levels of neural respiratory drive (NRD) in a cohort of healthy subjects and chronic obstructive pulmonary disease (COPD) patients, and to investigate the relationship between NRD and pulmonary function in COPD. EMG(di) was recorded at rest and normalised to peak EMG(di) recorded during maximum inspiratory manoeuvres (EMG(di) % max) in 100 healthy subjects and 30 patients with COPD, using a multipair oesophageal electrode. EMG(di) was normalised to the amplitude of the diaphragm compound muscle action potential (CMAP(di,MS)) in 64 healthy subjects. The mean+/-sd EMG(di) % max was 9.0+/-3.4% in healthy subjects and 27.9+/-9.9% in COPD patients, and correlated with percentage predicted forced expiratory volume in one second, vital capacity and inspiratory capacity in patients. EMG(di) % max was higher in healthy subjects aged 51-80 yrs than in those aged 18-50 yrs (11.4+/-3.4 versus 8.2+/-2.9%, respectively). Observations in the healthy group were similar when peak EMG(di) or CMAP(di,MS) were used to normalise EMG(di). Levels of neural respiratory drive were higher in chronic obstructive pulmonary disease patients than healthy subjects, and related to disease severity. Diaphragm compound muscle action potential could be used to normalise diaphragm electromyogram if volitional inspiratory manoeuvres could not be performed, allowing translation of the technique to critically ill and ventilated patients.

Lėtine obstrukcine plaučių liga serganičių ligonių reabilitacija

Pagrindiniai plaučių ligų reabilitacijos tikslai yra lengvinti simptomus, gerinti paciento gyvenimo kokybę ir skatinti fizinį bei emocinį aktyvumą. Sprendžiamos ir kitos problemos: fizinio krūvio toleravimo mažėjimo, santykinės socialinės izoliacijos, nuotaikos sutrikimų, ypač depresijos, raumenų nykimo ir kūno masės mažėjimo. Didžiąją dalį pacientų, kuriems skiriama pulmonologinė reabilitacija, sudaro ligoniai, sergantys lėtine obstrukcine plaučių liga (LOPL). Straipsnyje apžvelgiamos naujausios Amerikos torakalistų bei Europos pulmonologų sąjungos parengtos pulmonologinės reabilitacijos rekomendacijos.

Reversing concepts on COPD irreversibility

Common diseases are complex. The study of complexity is based on a new way of thinking that stands in sharp contrast to the philosophy underlying Newtonian science, which is based on reductionism, determinism and objective knowledge. Initially, we might aim to reduce complexity to understand nature 1. In the current issue of the European Respiratory Journal ( ERJ ), Tashkin et al. 2 report the baseline results for bronchial hyperresponsiveness in patients recruited in an ongoing, large chronic obstructive pulmonary disease (COPD) clinical trial, the Understanding the Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial 3. This report 2 challenges the vastly established concept that lung function in COPD is largely irreversible. Tashkin et al. 2 concluded that over one-half to nearly two-thirds of participating subjects met the most commonly used criteria for acute bronchodilator responsiveness, and more than one-third showed acute responsiveness by an increase in the percentage predicted criterion. Most certainly, the combined strategy employed in the UPLIFT trial involving the use of two bronchodilators (80 μg ipratropium and 400 μg salbutamol) to ensure maximum or near-maximum bronchodilation magnifies this biological finding. Currently, both American Thoracic Society/European Respiratory Society 4 and Global Initiative for Chronic Obstructive Lung Disease 5 …

Effect of add-on therapy of tiotropium in COPD treated with theophylline

Although combination therapy with bronchodilators is recommended for chronic obstructive pulmonary disease (COPD), there is insufficient evidence for the efficacy of some combinations of long-acting bronchodilators. We investigated the effects of a combination therapy with tiotropium and theophylline in COPD patients. In a 12-week, open-labeled, parallel-group randomized study, pulmonary functions and dyspnea scores were compared between the combination and theophylline alone therapy at baseline, and 4 and 8 weeks after randomization in COPD. Sixty-one COPD patients completed the trial (31 combination therapy, 30 theophylline alone; mean age 70 years; 58 males; mean dyspnea score 2.0 and forced expiratory volume in one second (FEV1) 1.5 L [62.5% predicted]). FEV1 in the combination group, but not in the theophylline alone, was significantly increased at 4 (1.56 +/- 0.13 L, p < 0.001) and 8 weeks (1.60 +/- 0.13 L, p < 0.001) from the baseline (1.40 +/- 0.12 L). In the combination group, but not the theophylline alone group, the dyspnea score was significantly improved after 4 (p < 0.01) and 8 weeks (p <0.05) compared with baseline. In 17 patients who did not receive theophylline at screening, treatment with 4 or 8 weeks of theophylline alone did not improve dyspnea score or FEV1. Addition of tiotropium therapy to theophylline treatment can improve dyspnea and pulmonary function in COPD. Although this study did not assess whether there was any benefit of adding theophylline to patients treated with tiotropium, tiotropium can be a useful addition in COPD already treated with theophylline.

Interleukin-18 production and pulmonary function in COPD

Interleukin (IL)-18 production and pulmonary function were evaluated in patients with chronic obstructive pulmonary disease (COPD) in order to determine the role of IL-18 in COPD. Immunohistochemical techniques were used to examine IL-18 production in the lungs of patients with very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV, n = 16), smokers (n = 27) and nonsmokers (n = 23). Serum cytokine levels and pulmonary function were analysed in patients with GOLD stage I-IV COPD (n = 62), smokers (n = 34) and nonsmokers (n = 47). Persistent and severe small airway inflammation was observed in the lungs of ex-smokers with very severe COPD. IL-18 proteins were strongly expressed in alveolar macrophages, CD8+ T-cells, and both the bronchiolar and alveolar epithelia in the lungs of COPD patients. Serum levels of IL-18 in COPD patients and smokers were significantly higher than those in nonsmokers. Moreover, serum levels of IL-18 in patients with GOLD stage III and IV COPD were significantly higher than in smokers and nonsmokers. There was a significant negative correlation between serum IL-18 level and the predicted forced expiratory volume in one second in patients with COPD. In contrast, serum levels of IL-4, IL-13 and interferon-gamma were not significantly increased in any of the three groups. In conclusion, overproduction of interleukin-18 in the lungs may be involved in the pathogenesis of chronic obstructive pulmonary disease.

Correlation of oxidative status with BMI and lung function in COPD

Objectives: The imbalance in oxidative status together with nutrition depletion and low body weight play a vital role in the pathogenesis and severity of chronic obstructive pulmonary disease (COPD). The study was undertaken to ascertain if a relationship existed between oxidative status and BMI in COPD. In addition, association of oxidative status and BMI with lung function of the disease was also examined. Materials and methods: In 202 COPD patients and 136 healthy controls plasma lipid peroxidation (LPO), reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT) activities, BMI and FEV 1% predicted were looked for interactions. Results: The patients had increased LPO ( p = 0.006) and decreased antioxidants (GSH, p = 0.005; GPx, p = 0.035 and CAT, p = 0.008, respectively). Of note are the correlations of oxidative stress markers with BMI and FEV 1% predicted in the patients. LPO inversely and GSH, GPx, and CAT positively correlated with both BMI ( p = 0.007, p < 0.001, p = 0.045 and p = 0.009, respectively), and FEV 1% of predicted (LPO, p = 0.001; GSH, p < 0.001; GPx, p = 0.043 and CAT, p < 0.001) in the patients. Further, a positive correlation existed between BMI and FEV 1% predicted ( p = 0.016) in COPD. Conclusion: The intimate relationship of oxidative status with BMI and lung function, and the direct correlation between BMI and FEV 1 may potentiate severity of the disease.

Assessment of Pulmonary Function in COPD

Pulmonary function testing is used in the diagnosis of chronic obstructive pulmonary disease (COPD) and the staging of COPD severity. The current diagnostic criterion for airflow obstruction is a ratio of forced expiratory volume in 1 second (FEV (1)) to forced vital capacity (FVC) < 70%. However this absolute definition can lead to false-negative determinations in younger patients and false-positive determinations in the elderly. Nevertheless, screening spirometry is advocated and becomes feasible in the physician office setting with the availability of compact, relatively affordable apparatus that meets the appropriate technical specifications. Spirometry should be complemented by measurement of lung volumes using body plethysmography in those with evidence of airflow obstruction. Small airways disease can be detected by various techniques that measure airway and total respiratory system resistance. There is renewed interest in the forced oscillation technique and impulse oscillometry because of their noninvasiveness and potential ability to distinguish small from larger airway disease. Finally, pulmonary function testing has an important role in preoperative risk assessment; for example, in patients being considered for lung volume reduction surgery or resection of a lung nodule.

Approaches to slowing the progression of COPD.

Chronic obstructive pulmonary disease (COPD) is a major health problem across the world and its medical, societal and economic impacts continue to grow. There are several hypotheses regarding the pathogenesis of COPD and important new information on airway inflammation, oxidative stress and proteolysis in the lungs that are important for the development of effective treatments. The differences in susceptibility to COPD among cigarette smokers and the common familial risk of developing disease point to important genetic influences. The identification of candidate gene loci and various gene polymorphisms have improved our understanding of the mechanisms by which genetic factors predispose for COPD. The beneficial effects of smoking cessation in slowing the decline in lung function and the progression of disease have been clearly established. Whether other factors such as mucus hypersecretion, respiratory infections and airway hyperreactivity contribute to disease progression independent of cigarette smoking is still being debated. There is new interest in dietary strategies to prevent or control COPD and preliminary information suggesting the usefulness of diets favoring antioxidant-rich foods. On the other hand several large, long-term, randomized, controlled clinical trials have failed to show a beneficial effect of either anticholinergics or corticosteroids in slowing the rate of decline in lung function in COPD. Corticosteroid treatment, however, appears to reduce the frequency of COPD exacerbations and there is some suggestion that it may also reduce the risk of death in patients with severe COPD.

The Role of Antibiotics in Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Our understanding of the pathogenesis and consequences of acute exacerbations of chronic obstructive pulmonary disease (COPD) has increased considerably in the past decade. Several new lines of evidence support bacterial causation of about half the exacerbations. Contrary to previous data, recent studies with improved methodology have demonstrated that exacerbations do contribute to the loss of lung function in COPD. Another interesting new observation is that colonization by bacterial pathogens may not be innocuous, and in fact may lead to airway inflammation and contribute to pathogenesis of COPD. Evidence that bacteria cause exacerbations, that exacerbations contribute to loss of lung function, and that chronic colonization by bacteria may be harmful, has emphasized the potential importance of appropriate antibiotics in the treatment of exacerbations. An unfortunate paucity of data does not allow evidence-based recommendations to be made for optimal choice of antibiotics for exacerbations of COPD. Emerging data that antibiotics differ in unconventional measures of efficacy such as time to next exacerbation, improvement in health-related quality of life, and bacteriologic eradication will help us make concrete recommendations in the future.