Airflow Limitation In Patients Research Articles

Effect of threshold on the correlation between airflow obstruction and low attenuation volume in smokers assessed by inspiratory and expiratory MDCT

The estimation of emphysematous changes is very sensitive to computed tomography (CT) threshold level. In clinical practice, the predetermined threshold is usually set at -950 Hounsfield units (HU) for the detection of low attenuation volume (LAV). However, threshold levels that are tightly connected to pulmonary function abnormalities have not been determined. To determine the threshold level for calculating an LAV that closely reflects airflow limitation in patients with chronic obstructive pulmonary disease (COPD). Seventy-six consecutive non-COPD smokers and COPD patients underwent paired inspiratory and expiratory multidetector CT (MDCT). LAV% was segmented every 10 HU between -1000 and -750 HU to examine the correlation between LAV% and indexes of obstructive impairment. LAV% gradually increased as the threshold level increased on both inspiratory and expiratory images. LAV% on inspiratory images was higher than that on expiratory images at all threshold levels between -1000 and -750 HU. The threshold level that correlated with obstructive impairment differed between the two images: -930 HU on inspiratory and -870 or -880 HU on expiratory images. LAV% dramatically changed according to the threshold level on both inspiratory and expiratory images, indicating that LAV% is dependent on the attenuation threshold level in patients with COPD. The threshold linking LAV% to airflow limitation was higher on expiratory than on inspiratory images.

Paired maximum inspiratory and expiratory plain chest radiographs for assessment of airflow limitation in chronic obstructive pulmonary disease

BackgroundThe usefulness of paired maximum inspiratory and expiratory (I/E) plain chest radiography (pCR) for diagnosis of chronic obstructive pulmonary disease (COPD) is still unclear. ObjectivesWe examined whether measurement of the I/E ratio using paired I/E pCR could be used for detection of airflow limitation in patients with COPD. MethodsEighty patients with COPD (GOLD stage I=23, stage II=32, stage III=15, stage IV=10) and 34 control subjects were enrolled. The I/E ratios of frontal and lateral lung areas, and lung distance between the apex and base on pCR views were analyzed quantitatively. Pulmonary function parameters were measured at the same time. ResultsThe I/E ratios for the frontal lung area (1.25±0.01), the lateral lung area (1.29±0.01), and the lung distance (1.18±0.01) were significantly (p<0.05) reduced in COPD patients compared with controls (1.31±0.02 and 1.38±0.02, and 1.22±0.01, respectively). The I/E ratios in frontal and lateral areas, and lung distance were significantly (p<0.05) reduced in severe (GOLD stage III) and very severe (GOLD stage IV) COPD as compared to control subjects, although the I/E ratios did not differ significantly between severe and very severe COPD. Moreover, the I/E ratios were significantly correlated with pulmonary function parameters. ConclusionsMeasurement of I/E ratios on paired I/E pCR is simple and reproducible, and can detect airflow limitation in patients with severe and very severe COPD.

Risk factors for persistent airflow limitation: Analysis of 306 patients with asthma.

Objectives : To determine the risk factors associated with persistent airflow limitation in patients with asthma. Method s: This study was designed and carried out in the department of respiratory medicine, fourth People’s Hospital of Jinan City, Shandong province, China between Jan 2012 and Dec 2012. Three hundred and six asthma patients participating in the study were divided into persistent airflow limitation group (PAFL) and no persistent airflow limitation group (NPAFL). The patients participated in pulmonary function tests and sputum induction examination. The clinical data including age, gender, onset age, disease course, smoking history, family history, regular corticosteroid inhalation, hospitalization history and presence of atopy were collected. Results : In 306 patients, 128 (40.5%) were included in PAFL group and 178(59.5%) in NPAFL group. Multivariate analysis demonstrated smoking (≥10 pack-years; OR, 7.1; 95% CI, 1.8 to 31.2), longer asthma duration (≥ 20years) (OR, 6.3; 95% CI, 1.7 to 28.5), absence of regular corticosteroid inhalation (OR, 3.5; 95% CI, 1.1 to 14.5) and neutrophil in induced sputum≥65% (OR, 1.8; 95% CI, 1.0 to 2.8) were independent risk factors for PAFL. Conclusions : Smoking, longer asthma duration and increased neutrophil in induced sputum are risk factors for PAFL, while regular corticosteroid inhalation is protective factor. Smoking cessation and regular corticosteroid inhalation may play an important role in preventing the occurrence of persistent airflow limitation group (PAFL).

Echocardiography, Spirometry, and Systemic Acute-Phase Inflammatory Proteins in Smokers with COPD or CHF: An Observational Study

Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) may coexist in elderly patients with a history of smoking. Low-grade systemic inflammation induced by smoking may represent the link between these 2 conditions. In this study, we investigated left ventricular dysfunction in patients primarily diagnosed with COPD, and nonreversible airflow limitation in patients primarily diagnosed with CHF. The levels of circulating high-sensitive C-reactive protein (Hs-CRP), pentraxin 3 (PTX3), interleukin-1β (IL-1 β), and soluble type II receptor of IL-1 (sIL-1RII) were also measured as markers of systemic inflammation in these 2 cohorts. Patients aged ≥50 years and with ≥10 pack years of cigarette smoking who presented with a diagnosis of stable COPD (n=70) or stable CHF (n=124) were recruited. All patients underwent echocardiography, N-terminal pro-hormone of brain natriuretic peptide measurements, and post-bronchodilator spirometry. Plasma levels of Hs-CRP, PTX3, IL-1 β, and sIL-1RII were determined by using a sandwich enzyme-linked immuno-sorbent assay in all patients and in 24 healthy smokers (control subjects). Although we were unable to find a single COPD patient with left ventricular dysfunction, we found nonreversible airflow limitation in 34% of patients with CHF. On the other hand, COPD patients had higher plasma levels of Hs-CRP, IL1 β, and sIL-1RII compared with CHF patients and control subjects (p < 0.05). None of the inflammatory biomarkers was different between CHF patients and control subjects. In conclusion, although the COPD patients had no evidence of CHF, up to one third of patients with CHF had airflow limitation, suggesting that routine spirometry is warranted in patients with CHF, whereas echocardiography is not required in well characterized patients with COPD. Only smokers with COPD seem to have evidence of systemic inflammation.

Increased periostin associates with greater airflow limitation in patients receiving inhaled corticosteroids

Periostin, an extracellular matrix protein, contributes to subepithelial thickening in asthmatic airways, and its serum levels reflect airway eosinophilic inflammation. However, the relationship between periostin and the development of airflow limitation, a functional consequence of airway remodeling, remains unknown. We aimed to determine the relationship between serum periostin levels and pulmonary function decline in asthmatic patients on inhaled corticosteroid (ICS) treatment. Two hundred twenty-four asthmatic patients (average age, 62.3 years) treated with ICS for at least 4 years were enrolled. Annual changes in FEV1, from at least 1 year after the initiation of ICS treatment to the time of enrollment or later (average, 16.2 measurements over 8 years per individual), were assessed. At enrollment, clinical indices, biomarkers that included serum periostin, and periostin gene polymorphisms were examined. Associations between clinical indices or biomarkers and a decline in FEV1 of 30 mL or greater per year were analyzed. High serum periostin levels (≥ 95 ng/mL) at enrollment, the highest treatment step, higher ICS daily doses, a history of admission due to asthma exacerbation, comorbid or a history of sinusitis, and ex-smoking were associated with a decline in FEV1 of 30 mL or greater per year. Multivariate analysis showed that high serum periostin, the highest treatment step, and ex-smoking were independent risk factors for the decline. Polymorphisms of periostin gene were related to higher serum periostin levels (rs3829365) and a decline in FEV1 of 30 mL or greater per year (rs9603226). Serum periostin appears to be a useful biomarker for the development of airflow limitation in asthmatic patients on ICS.

Indacaterol on dyspnea in chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomized placebo-controlled trials.

BackgroundIndacaterol is a novel, once-daily (od), inhaled, long-acting ß2-agonist bronchodilator for maintenance treatment of airflow limitation in patients with COPD. The aim of this study was to evaluate the efficacy of indacaterol on dyspnea, using available randomized placebo-controlled trials.MethodsA systematic search was made of MEDLINE, EMBASE, the Cochrane trials databases, and a manual search of journals. Randomized placebo-controlled trials of 12 weeks or more comparing indacaterol with placebo were reviewed, and eligible studies were included in a meta-analysis. The odds ratio (OR) for likelihood of achieving TDI score ≥ 1 after 12 weeks of treatment was used as an outcome measure to compare indacaterol to placebo.ResultsSix trials were included in the analysis. Relative to placebo, the overall ORs for response were: indacaterol 75 μg od 1.784 (95% CI 1.282 to 2.482); indacaterol 150 μg od 2.149 (95% CI 1.746 to 2.645); and indacaterol 300 μg od 2.458 (95% CI 2.010 to 3.006). Overall OR for response in TDI tended to increase with higher indacaterol doses.ConclusionsPatients receiving indacaterol had clinically significant improvements in symptoms of dyspnea compared to placebo. Incremental benefits in TDI were observed with increasing doses. Indacaterol may provide patients and physicians with a useful treatment option in symptomatic patients with dyspnea.

English

Total of 104 patients were studied with an average age of 47.952 + 16.9112, with 77% of the patients being male. The maximum no of patient were of the middle aged adult males age group 31 - 40.The study comprised of 104 individuals of which 79 patients were males and 25 were females. The average weight of the 104 patients was 68.615 kg . The body mass index of our patients had a mean of 26.146 with a minimum BMI of 14.382 a maximum BMI of 48.828. Forced expiratory volume in 1 st second in our OBESE asthmatics was 1.78 ± 0.8150.& Forced vital capacity in the obese group was 2.102 ± 0.8638 .FEV1% was > 70 % in all the patients of the study population demonstrating no fixed airflow limitation in patients of our study population . ERV in the obese groups was .441 ± 0.2190 liters. The inspiratory capacity in the obese group was 1.771 ± 0.6628 liters . No significant statistical correlation was demonstrated in between the obese and no obese group . Significant correlation was demonstrated between BMI & Waist Circumference. BMI correlated with FEV1, FVC, FEV1% in the study population and a negative correlation was demonstrable. A statistically significant co relation could not be established between BMI & the dynamic spirometric variables. BMI correlated with ERV & VC in the study population and a negative correlation was demonstrable. A statistically significant co relation could not be established between BMI & the static spirometric variables. Waist circumference correlated with the FEV1, FVC, FEV1% in the study population and a negative correlation was demonstrable. A statistically significant co relation could not be established between waist circumference & the dynamic spirometric variables. Waist circumference correlated with ERV & VC in the study population and a negative correlation was demonstrable. A statistically significant co relation could not be established between waist circumference & the static spirometric variables.

Effects of Expiratory Positive Airway Pressure on Dynamic Hyperinflation During Exercise in Patients With COPD

Expiratory positive airway pressure (EPAP) is a form of noninvasive positive-pressure ventilatory support that, in spite of not unloading respiratory muscles during inspiration, may reduce the inspiratory threshold load and attenuate expiratory dynamic airway compression, contributing to reduced expiratory air-flow limitation in patients with COPD. We sought to determine the effects of EPAP on operational lung volumes during exercise in COPD patients. This was a nonrandomized, experimental comparison of 2 exercise conditions (with and without EPAP); subjects completed a treadmill exercise test and performed, before and immediately after exercise, lung volume measurements. Those who overtly developed dynamic hyperinflation (DH), as defined by at least a 15% reduction from pre-exercise inspiratory capacity (IC), were invited for an additional research visit to repeat the same exercise protocol while receiving EPAP through a spring loaded resistor face mask. The primary outcome was IC variance (pre-post exercise) comparison under the 2 exercise conditions. Forty-six subjects (32 males), a mean 65.0 ± 8.2 years of age, and with moderate to severe COPD (FEV(1) = 38 ± 16% predicted) were initially enrolled. From this initial sample, 17 (37%) presented overt DH, as previously defined. No significant difference was found between these subjects and the rest of the initial sample. Comparing before and after exercise, there was significantly less reduction in IC observed when EPAP was used (-0.18 ± 0.35 L vs -0.57 ± 0.45 L, P = .02), allowing greater IC final values (1.45 ± 0.50 L vs 1.13 ± 0.52 L, P = .02). The application of EPAP reduced DH, as shown by lower operational lung volumes after submaximal exercise in COPD patients who previously manifested exercise DH.

World Spirometry Day: intention to test should be intention to treat.

The increasing frequency of chronic respiratory disease1 is the justification for World Spirometry Day (WSD), a global initiative organised by the Forum of International Respiratory Societies (FIRS). WSD originated from the experience of public spirometry events during Congresses of the European Respiratory Society, where free spirometry was offered to the general public with the aim of raising awareness about lung health and diseases. During the first WSD, on 14 October 2010,2 a total of 102 487 lung function tests were performed: 67% in Europe, 13% in South America, 8% in Australasia, 6% in North America, 5% in Asia, and 0.01% (12 tests) in Africa.3 The second WSD, on 27 June 2012, will be an opportunity to raise awareness about lung health, although its objectives need to be clarified. While spirometry is recommended for the diagnosis of airflow limitation in patients with respiratory symptoms, several professional societies recommend against using it in individuals without respiratory symptoms, as it involves substantial cost and may result in over-diagnosis due to false-positive results, unnecessary disease labelling, and inadequate use of medicine without clear benefit in reducing future risks of exacerbation and lung function decline.4 Further, providing individuals with their spirometry results was not found to independently improve smoking cessation or the likelihood of continued abstinence.4 WSD should therefore aim at raising awareness about lung health, but not at using spirometry screening among asymptomatic individuals. As screening without adequate follow-up care will yield no benefit, intention to test should be intention to treat. The contribution of WSD in improving the management of patients with chronic airflow limitation in resource-limited settings should also be clarified. Unfortunately, quality-assured essential medicine, such as inhaled corticosteroids and bronchodilators, for patients with airflow limitation may not be accessible or affordable in low- and middle-income countries.5 Even simple diagnostic tools such as peak flow meters are usually not available, let alone spirometers, and large numbers of patients in resource-limited settings repeatedly make unplanned health visits due to asthma attacks or exacerbations of chronic obstructive pulmonary disease in the absence of long-term management and care. Intention to treat therefore demands a system-wide approach to address the needs of the vulnerable.

Non‐atopic males with adult onset asthma are at risk of persistent airflow limitation

Patients with asthma have on average a more rapid decline in FEV (1) as compared with the general population. Recent cluster analysis has revealed different asthma phenotypes that can be distinguished by age of onset and reversibility of airflow limitation. This study aimed at detecting risk factors associated with persistent airflow limitation in patients with the adult onset asthma phenotype. We recruited 88 patients with adult onset (≥ 18 years) asthma from an academic pulmonary outpatient clinic in the Netherlands. The associations of age, age of asthma onset, asthma duration, gender, race, atopy, smoking pack-years, BMI, use of oral corticosteroids with post-bronchodilator FEV (1) /FVC were investigated. Multiple linear regression analysis showed an association of absence of atopy (r = -0.27, B = -0.26, P = 0.01) and male gender (r = 0.31, B = 0.30, P = 0.004) with post-bronchodilator FEV (1) /FVC. Multiple logistic regression analysis showed that male patients were 10.8 (CI: 2.6-45.2) times the odds than women to have an FEV (1) /FVC < 0.7, and non-atopic patients were 5.2 (CI: 1.3-20.3) times the odds to have an FEV (1) /FVC < 0.7 than atopic patients. We conclude that in patients with adult onset asthma, male gender and absence of atopy are associated with persistent airflow limitation. This might suggest that amongst patients with adult onset asthma, non-atopic male patients are at increased risk of accelerated decline in lung function.

An epidemiological study of the effects of statin use on airflow limitation in patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is considered to be a systemic inflammatory disease, and systemic inflammation has been noted as a factor contributing to cardiovascular disease, which is one of the comorbidities associated with COPD. On the other hand, pleiotropic effects, such as the anti-inflammatory effects of statins, have attracted attention in recent years, and there have been a variety of reports regarding the usefulness of statins for patients with COPD. We investigated whether the use or non-use of statins influenced the prevalence of airflow limitation. All outpatients who were over the age of 40 years and who regularly visited a primary health care facility were invited to participate. Each participant underwent spirometry and completed a questionnaire regarding their clinical status, which was used to screen for COPD. A variety of factors that are potentially related to airflow limitation were assessed. Of the 853 patients included in the study, 81 (9.5%) had airflow limitation. The prevalence of airflow limitation was 2.3% among the 89 patients with a history of statin use, which was five times lower than the prevalence of airflow limitation among patients who had not used statins (10.5%). Among the 347 patients with a history of past or current smoking, airflow limitation was not observed in the 30 patients who had used statins. However, by multivariate analysis, statin use was not significantly associated with a lower prevalence of airflow limitation. This is the first cross-sectional study from Japan that has demonstrated that statin use has a potential impact on airflow limitation in patients with COPD.

Contributors of the Severity of Airflow Limitation in COPD Patients

of the severity of airflow limitation. Results: Multiple linear regression analysis showed that CT measurements of mean lung density ratio (standardized coefficient β=−0.46; p<0.001), emphysema severity (volume fraction of the lung less than −950 HU at full inspiration; β=−0.24; p<0.001), and airway wall thickness (mean wall area %; β=−0.19, p=0.001), as well as current smoking status (β=−0.14; p=0.009) were independent contributors to FEV1. Conclusion: Mean lung density ratio, emphysema severity, and airway wall thickness evaluated by volumetric CT and smoking status could independently contribute to the severity of airflow limitation in patients with COPD.

Undiagnosed airflow limitation in patients at cardiovascular risk

Chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVD) share risk factors and impair each other's prognosis. To assess the prevalence of airflow limitation (AL) compatible with COPD in a population at cardiovascular risk and to identify determinants of AL. All consecutive patients referred to the cardiovascular prevention unit of a university hospital in 2009 were studied in a cross-sectional analysis. Patients answered questionnaires on socioeconomic status, medical history and lifestyle, and underwent extensive physical examinations, biological measures and spirometry testing. AL was defined as FEV1/FVC<0.70, without any history of asthma. Determinants of AL were assessed using logistic regression. The sample comprised 493 participants (mean age 57.4±11.1 years); 60% were men, 18% were current smokers, 42% were ex-smokers and 10% of patients had a history of CVD. Ten-year risk of coronary heart disease (CHD) according to the Framingham equation was intermediate (10-20%) for 25% of patients and high (>20%) for 10%. Prevalence of AL was 5.9% (95% confidence interval [CI] 4.0-8.3%) in the whole population and 4.3% (2.6-6.6%) among subjects in primary cardiovascular prevention. AL was independently associated with CVD (adjusted odds ratio 4.18, 95% CI 1.72-10.15; P=0.002) but not with Framingham CHD risk. More than 80% of patients screened with AL had not been diagnosed previously and more than one in two patients was asymptomatic. Patients with CVD are at increased risk of AL and thus should benefit from AL screening as they are frequently asymptomatic.

Bronchial secretory immunoglobulin a deficiency correlates with airway inflammation and progression of chronic obstructive pulmonary disease.

Although airway inflammation can persist for years after smoking cessation in patients with chronic obstructive pulmonary disease (COPD), the mechanisms of persistent inflammation are largely unknown. We investigated relationships between bronchial epithelial remodeling, polymeric immunoglobulin receptor (pIgR) expression, secretory IgA (SIgA), airway inflammation, and mural remodeling in COPD. Lung tissue specimens and bronchoalveolar lavage were obtained from lifetime nonsmokers and former smokers with or without COPD. Epithelial structural changes were quantified by morphometric analysis. Expression of pIgR was determined by immunostaining and real-time polymerase chain reaction. Immunohistochemistry was performed for IgA, CD4 and CD8 lymphocytes, and cytomegalovirus and Epstein-Barr virus antigens. Total IgA and SIgA were measured by ELISA and IgA transcytosis was studied using cultured human bronchial epithelial cells. Areas of bronchial mucosa covered by normal pseudostratified ciliated epithelium were characterized by pIgR expression with SIgA present on the mucosal surface. In contrast, areas of bronchial epithelial remodeling had reduced pIgR expression, localized SIgA deficiency, and increased CD4(+) and CD8(+) lymphocyte infiltration. In small airways (<2 mm), these changes were associated with presence of herpesvirus antigens, airway wall remodeling, and airflow limitation in patients with COPD. Patients with COPD had reduced SIgA in bronchoalveolar lavage. Air-liquid interface epithelial cell cultures revealed that complete epithelial differentiation was required for normal pIgR expression and IgA transcytosis. Our findings indicate that epithelial structural abnormalities lead to localized SIgA deficiency in COPD airways. Impaired mucosal immunity may contribute to persistent airway inflammation and progressive airway remodeling in COPD.

Prevalence of Airflow Limitation in Patients Diagnosed and Treated for Symptoms of Chronic Bronchitis by General Practitioners in Tochigi Prefecture, Japan

Physicians have provided care to only 0.2 million of the 5.3 million Japanese over the age of 40 years old who have chronic obstructive pulmonary disease (COPD). Among such individuals, many patients with respiratory symptoms diagnosed as chronic bronchitis (CB) are prescribed mainly expectorants. To determine the current status of COPD subjects diagnosed with and treated for CB, we investigated the prevalence of airflow limitation (AFL) in CB patients diagnosed by general practitioners (GPs) and the therapies administered to them. Patients receiving treatment by GPs as CB completed a questionnaire and the FEV(1)/FEV(6) ratio was measured by their GPs with a Piko-6. The prevalence of AFL (FEV(1)/FEV(6) <73%) and the correlation between FEV(1)/FEV(6) and FEV(1)/FVC were examined. Prescription behavior and comorbid lifestyle diseases were also examined. Data from 197 patients with CB were analyzed. Among those who underwent spirometry, the correlation between FEV(1)/FVC and FEV(1)/FEV(6) was r(2)=0.38 (p<0.0001), and the sensitivity and specificity of the Piko-6 were 85.7% and 61.1%, respectively. The prevalence of AFL was 47.2% and increased to 54.1% among patients aged 70-79 years. Expectorants were prescribed for 39.8% of CB patients with AFL, but inhaled bronchodilators were prescribed for only 22.6%. Smoking history and age were significantly higher in the group with AFL than in those without AFL (p<0.05). The prevalence of comorbid lifestyle diseases was 73.1% in patients with AFL. AFL was prevalent among patients with CB. Therefore, GPs should test pulmonary function in CB patients to ensure that the appropriate therapy is administered.

High Prevalence of Undiagnosed Airflow Limitation in Patients With Cardiovascular Disease

The prevalence of airflow limitation (AL) in patients with cardiovascular disease (CVD) is unknown, and whether AL is adequately diagnosed and treated in these patients has not been investigated before, to our knowledge. We compared clinical and spirometric data in three groups of individuals. Two of them were participants in the follow-up of an ongoing population-based study according to the presence or absence of CVD. The third group included patients with coronary artery disease (CAD) confirmed by coronariography regularly visited at a tertiary referral university hospital. AL was defined according to the Global Initiative for Obstructive Lung Disease guidelines. We studied 450 population participants without CVD, 52 population participants with CVD, and 119 hospital patients with CAD. The prevalence of AL in these three groups was 17.5% (95% CI, 14.0-21.0), 19.2% (95% CI, 8.1-30.7), and 33.6% (95% CI, 25.0-42.2), respectively (P < .05). Underdiagnosis of AL ranged from 60% in population participants with CVD up to 87.2% in hospital patients with CAD. Sixty percent of those with spirometrically confirmed AL (in all three groups) did not receive any respiratory treatment. AL is frequent in individuals with CVD, particularly in those with CAD attended in the hospital, is largely underdiagnosed and therefore is highly undertreated. Clinicaltrials.gov; Identifier: NCT00787748.

Ventilation-perfusion imbalance and chronic obstructive pulmonary disease staging severity

Chronic obstructive pulmonary disease (COPD) is characterized by a decline in forced expiratory volume in 1 s (FEV(1)) and, in many advanced patients, by arterial hypoxemia with or without hypercapnia. Spirometric and gas exchange abnormalities have not been found to relate closely, but this may reflect a narrow range of severity in patients studied. Therefore, we assessed the relationship between pulmonary gas exchange and airflow limitation in patients with COPD across the severity spectrum. Ventilation-perfusion (V(A)/Q) mismatch was measured using the multiple inert gas elimination technique in 150 patients from previous studies. The distribution of patients according to the GOLD stage of COPD was: 15 with stage 1; 40 with stage 2; 32 with stage 3; and 63 with stage 4. In GOLD stage 1, AaPo(2) and V(A)/Q mismatch were clearly abnormal; thereafter, hypoxemia, AaPo(2), and V(A)/Q imbalance increased, but the changes from GOLD stages 1-4 were modest. Postbronchodilator FEV(1) was related to Pa(O(2)) (r = 0.62) and Pa(CO(2)) (r = -0.59) and to overall V(A)/Q heterogeneity (r = -0.48) (P < 0.001 each). Pulmonary gas exchange abnormalities in COPD are related to FEV(1) across the spectrum of severity. V(A)/Q imbalance, predominantly perfusion heterogeneity, is disproportionately greater than airflow limitation in GOLD stage 1, suggesting that COPD initially involves the smallest airways, parenchyma, and pulmonary vessels with minimal spirometric disturbances. That progression of V(A)/Q inequality with spirometric severity is modest may reflect pathogenic processes that reduce both local ventilation and blood flow in the same regions through airway and alveolar disease and capillary involvement.

Association of glutathione-S-transferase omega haplotypes with susceptibility to chronic obstructive pulmonary disease

Cigarette smoking is the main risk factor for developing the inflammatory lung disease chronic obstructive pulmonary disease (COPD). Differences in susceptibility among smokers have been attributed to a genetic predisposition. A recent publication on the Framingham Heart Study found a strong association of the Asn142Asp SNP in Glutatthione-S-transferase Omega (GSTO) 2 with forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC). FEV1 is the main parameter reflecting the degree of airflow limitation in patients with COPD. Therefore the present study was undertaken to investigate whether the Asn142Asp polymorphism in GSTO2 occurs more frequently in patients with COPD than healthy subjects and to replicate the finding that it strongly correlates with FEV1. Furthermore, the Ala140Asp substitution in GSTO1 was examined. Genotyping was carried out in 195 healthy controls and 355 patients with COPD. The results demonstrate that the Asn142Asp polymorphism in GSTO2 and the GSTO1140Asp/GSTO2142Asp haplotype were associated with increased risk of COPD. However, single-marker and haplotype-based analyses failed to reveal an association between lung function parameters and investigated non-synonymous coding SNPs in the GSTO genes. In conclusion, GSTO2 is a candidate gene for COPD, but is not associated with FEV1.

Expression and significance of beta(2)-adrenoreceptor in inflammatory cells of patients with chronic obstructive pulmonary disease

To investigate the relationship between beta(2)-adrenoceptor (beta(2)-AR) expression in inflammatory cells and airflow limitation in patients with chronic obstructive pulmonary disease (COPD). According to the severity of COPD, 37 patients with stable COPD were divided into three groups. Samples of peripheral blood and induced sputum were collected from 37 COPD patients, 11 of II grade, 12 of grade III, and 14 of grade IV. Counting and classification of white blood cells in the peripheral blood and induced sputum were made. Radioligand binding assay was used to detect the maximum binding capacity (Bmax) reflecting the density, and balance dissociation constant (Kd) reflecting the affinity of beta(2)-AR in the peripheral blood mononuclear cells (PBMC) from both kinds of specimens. Thirteen normal smokers were used as control group. No significant differences were found in peripheral blood leukocyte count, classification and induced sputum cell count among the 3 COPD groups and control group, but the neutrophil cell count levels of induced sputum of the COPD groups were all significantly higher than that of the control group (all P = 0.00). For the control, and COPD grade II, III, and IV groups, the Bmax levels of PBMC beta(2)-AR were (106 +/- 52), (156 +/- 72), (135 +/- 57) and (123 +/- 58) fmol/mg respectively (F = 1.45, P = 0.24); the Kd levels of PBMC beta(2)-AR were (548 +/- 267), (343 +/- 144), (297 +/- 150), and (375 +/- 95) pmol/L respectively (F = 4.84, P = 0.01); the Bmax levels of beta(2)-AR of induced sputum cells were (126 +/- 46), (116 +/- 54), (106 +/- 36), and (76 +/- 30) respectively (F = 3.46, P = 0.02); and the Kd levels of beta(2)-AR of induced sputum cells were (570 +/- 290), (405 +/- 197), (404 +/- 139), and (347 +/- 123) respectively (F = 2.97, P = 0.04). There was a positive correlation between the forced expiratory volume in one second in percentage of predicted and density of beta(2)-AR in induced sputum cells from the COPD patients (r = 0.43, P = 0.01). There was a positive correlation between the Bmax of beta(2)-AR in PBMC and induced sputum cells (r = 0.40, P = 0.02). The expression of beta(2)-AR in PBMC and induced sputum cells from COPD patients is down-regulated with progression of the disease. The expression of beta(2)-AR in the induced sputum cells changes more significantly than that in the PBMC. The expression of beta(2)-AR in inflammatory cells in the airway may play a more important role in the COPD progress.

Association Between Neutrophilic Airway Inflammation and Airflow Limitation in Adults With Asthma

There is debate about the mechanisms of persistent airflow limitation in patients with asthma. Chronic inflammation is assumed to be important, although there is limited and contradictory information about the relationship between airway inflammation and postbronchodilator FEV1. We have assessed the cross-sectional relationship between prebronchodilator and postbronchodilator FEV1 and measures of airway inflammation after allowing for the effects of potential confounding factors. Multivariate analysis was performed on data collected from 1,197 consecutive patients with asthma seen at the respiratory outpatient clinic at Glenfield Hospital between 1997 and 2004. Relationships between induced sputum total neutrophil and differential eosinophil cell counts, and prebronchodilator and postbronchodilator lung function were examined. Sputum total neutrophil but not differential eosinophil count was associated with lower postbronchodilator FEV1. Both differential eosinophil and total neutrophil count were associated with lower prebronchodilator FEV1. These effects were independent after adjustment for age, smoking, ethnicity, asthma duration, and inhaled corticosteroid use. A 10-fold increase in neutrophil count was associated with a 92 mL reduction (95% confidence interval, 29 to 158; p = 0.007) in postbronchodilator FEV1. In this large heterogeneous population of adults with asthma, we have shown that prebronchodilator FEV1 is associated with neutrophilic and eosinophilic airway inflammation, whereas sputum total neutrophil counts alone are associated with postbronchodilator FEV1. This supports the hypothesis that neutrophilic airway inflammation has a role in the progression of persistent airflow limitation in asthma and raises the possibility that this progression and the development of COPD share a common mechanism.