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Dyslipidemia is often comorbid with obstructive sleep apnea (OSA), but few population-based studies have investigated their relationship. Short sleep duration is associated with hypertension and diabetes; however, its association with dyslipidemia is not well known. We investigated relationships among OSA, sleep duration, and the lipid profile in a community-based study.We measured the respiratory disturbance index (RDI) and sleep duration by a type 3 portable device and actigraph in 275 men in a Japanese company. Fasting blood parameters were obtained from periodic inspection data.According to Japanese criteria, 143 subjects had dyslipidemia. Percent sleep time of oxygen saturation as measured by pulse oximetry (SpO2)lt; 90% and prevalence of severe OSA were greater and sleep duration and mean SpO2 during sleep were lower in subjects with dyslipidemia than in those without. Univariate analysis showed that the RDI was positively correlated with serum triglyceride (TG) levels (ρ = 0.20, Plt; .01), and sleep duration was negatively correlated with serum total cholesterol (TC) levels (γ = -0.13, P = .03) and serum low-density lipoprotein cholesterol levels (γ = -0.12, P = .04). Stepwise multiple regression analysis revealed that TG was correlated with RDI (β = 0.14, P = .02), BMI (β = 0.20, Plt; .01), and alcohol intake (β = 0.20, Plt; .01), and that TC was correlated with sleep duration (β = -0.13, P = .03), age (β = 0.15, P = .02), and waist/hip ratio (β = 0.15, P = .02).Short sleep duration was associated with TC levels and RDI was positively associated with TG levels among working-aged men in an urban Japanese company. Correcting the status of OSA and/or short sleep duration might improve the lipid profile and cardiovascular consequences.

Background Mycobacterium avium-intracellulare complex (MAC) is a ubiquitous pathogen found in soil and water. Environmental exposure is the primary route for MAC infection. However, specific environmental risk factors have been poorly determined in immunocompetent patients with pulmonary MAC disease. Methods A case-control study was performed with 106 patients with pulmonary MAC disease (men [women], 23 [83]; age, 64.3 ± 9.2 years) and 53 age-matched control patients with bronchiectasis but not pulmonary MAC infection (men [women], 7[46]; age, 63.0 ± 11.0 years). All participants completed a standardized questionnaire that included questions about medical history, smoking history, alcohol usage, age at menopause, and environment exposures. Environment exposures included soil exposure from farming or gardening; water exposure from bathing, showering, hot tub use, dishwashing, swimming, and drinking water; and pet exposure. Results No differences were identified in the patient characteristics and underlying diseases. More case patients experienced high soil exposure (≥ 2 per week) than control patients (23.6% vs 9.4%, P = .032); this remained significant after multivariate analysis (OR, 5.9; 95% CI, 1.4-24.7; P = .015). There were no significant differences in other environmental exposures. Case patients with high soil exposure were significantly older than those with low soil exposure (67.3 ± 7.3 years vs 64.3 ± 9.5 years, P = .037). Other characteristics, underlying diseases, and mycobacterial species did not differ between the two groups. Conclusions Patients with pulmonary MAC disease had significantly more soil exposure than noninfected control patients, which suggests that environmental soil exposure is a likely risk factor for the development of pulmonary MAC disease.

Background Sputum cell-subtype profiles in cough-variant asthma (CVA) are unknown. Methods Ninety-eight inhaled corticosteroid (ICS)-naive CVA patients were classified according to sputum eosinophil (eos)/neutrophil (neu) counts, as reported in subjects with asthma, as eosinophilic (E) (eos ≥ 1.0%, neu Results Subtype N patients, predominantly women, were marginally older than the other subtypes, but FEV 1 , airway responsiveness, and total and specific IgE results did not differ. ECP levels were higher in M and E than in N and P subtypes, being similar between M and E or N and P subtypes. Levels of IL-8 and NE were higher in M than in other subtypes, being similar among the latter. ICS doses were initially similar in all subtypes (800 μg equivalent of beclomethasone) but were higher in M than in N and P subtypes throughout follow-up, with E being intermediate between M and N or P subtypes. ICS doses decreased (halved or quartered) in E, N, and P patients followed for 24 months ( P Conclusions In addition to eosinophils, neutrophils, which are possibly activated in the presence of eosinophils, may participate in the pathophysiology of CVA.

Sensitization to Trichophyton, a major dermatophyte, has been associated with asthma. Whether such sensitization is generally associated with the severity of asthma, like other molds such as Alternaria, is unknown.We compared 258 patients with asthma, which was classified by severity as mild (n = 123), moderate (101), or severe (34), and 114 healthy control subjects, with regard to specific IgE titers against Trichophyton rubrum and other common allergens such as mixed molds, house-dust mite, cat dander, dog dander, Japanese cedar pollen, mixed Graminea pollens and mixed weed pollens.Positive rate of Trichophyton-specific IgE was higher in the patients with moderate asthma (15.8%) than in the control subjects (7.0%, p = 0.04) and patients with mild asthma (4.9%, p0.006), and it was also higher in the patients with severe asthma (32.4%) than in control subjects (p = 0.0001), and patients with mild asthma (p0.0001) and moderate asthma (p = 0.04), but it did not differ between the control subjects and patients with mild asthma. The positive rates of mixed molds, cat dander, and dog dander were almost invariably higher in patients in all asthma subgroups than in the control subjects but did not differ among patients in the three asthma subgroups. The positive rates of other allergens were not different in all groups. Reanalysis of positive rate of Trichophyton-specific IgE after excluding 52 subjects with positive results for mixed molds showed a similar statistical trend to that of the original cohort. This may negate the potential effect of cross-reactivity to these molds. Multivariate analysis of asthma subgroups identified positive IgE results for Trichophyton as an independent determinant of asthma severity.Specific IgE response to Trichophyton may be associated with more severe asthma.

Background Osteoporosis is one of the important systemic features of COPD. Although COPD itself is regarded as one risk factor for osteoporosis, the relationship between the extent of emphysema and reduced bone density is still unclear. Our first aim was therefore to measure vertebral bone density and the percentage of low-attenuation area (LAA%) in the lungs using chest CT scans in COPD patients. Our second aim was to investigate the relationships among CT scan measurements, anthropometric parameters, and pulmonary function. Methods Chest CT scans and pulmonary function tests were performed in 65 male patients with COPD. Using CT images, the CT scan density of the thoracic and lumbar vertebrae (T4, T7, T10, and L1) and the LAA% were measured quantitatively, and their correlations were analyzed. Results Linear regression analyses revealed that LAA% had a significant negative correlation with bone mineral density (BMD) [r = −0.522]. In addition, multiple regression analysis showed that only LAA% and body mass index (BMI) were predictive of BMD among age, BMI, smoking index, FEV1, arterial blood gas, and LAA%. Conclusions The extent of pulmonary emphysema significantly correlated with reduced bone density. Our study suggested that COPD itself could be a risk factor for osteoporosis and that chest CT scanning is useful for the management of COPD as a systemic disease.

To evaluate the long-term clinical course of patients with idiopathic pulmonary fibrosis (IPF) complicated with pulmonary arterial hypertension.Prospective analysis of consecutive IPF patients undergoing initial workup with right-heart catheterization (RHC) and pulmonary function testing (PFT). Pulmonary arterial pressure (PAP) and diffusion capacity of the lung for carbon monoxide (Dlco) were focused on.University hospital.Seventy-eight patients with IPF (67 men, 11 women; diagnosis by pathology, n = 59; clinical diagnosis, n = 19) had been followed up after initial workup for a maximum of 14 years.RHC data on 61 patients and PFT data on 52 patients were available. Five-year survival rates were 62.2% in the normal-PAP group (mean PAP17 mm Hg, n = 37) and 16.7% in the high-PAP group (mean PAP17 mm Hg, n = 24) [p0.001]; 70.4% in the preserved-Dlco group (percentage of predicted40%, n = 27) and 20.0% in the low-Dlco group (percentage of predicted40%, n = 25) [p0.001]; and 82.6% in group 1 (normal PAP and preserved Dlco, n = 23) and 15.6% in group 2 (high PAP, low Dlco, or both, n = 32) [p0.0001]. The relative risks of mortality within 5 years after RHC were 2.20 (95% confidence interval [CI], 1.40 to 3.45) in the high-PAP group, 2.70 (95% CI, 1.46 to 4.99) in the low-Dlco group, and 4.85 (95% CI, 1.97 to 11.97) in group 2.Dlco was a critical factor for evaluating disease status and prognosis, and PAP status provided feasible information in the initial workup of IPF patients.

Airflow limitation is found in some patients with sarcoidosis, and it is associated with a poor prognosis. The aim of this study was to investigate clinical and radiographic indices associated with airflow limitation in patients with sarcoidosis.A prospective, observational study was performed on 228 consecutive sarcoidosis patients followed up at our patient clinic at the Central Clinic of Kyoto. Patients underwent pulmonary function tests, and high-resolution CT (HRCT) of the lung was evaluated for the presence of lymph node enlargement, lung opacity, reticular shadow, and thickening of bronchovascular bundles (BVB). Airflow limitation was defined as FEV(1)/FVC70%. Airway reversibility was tested in subjects with airflow limitation. The frequency of airflow limitation was evaluated, and clinical and radiographic parameters were compared between patients with and without airflow limitation.Among all 228 subjects, 20 subjects (8.8%) had airflow limitation, and none showed airway reversibility. Patients with airflow limitation were predominantly male, smokers, and had advanced chest radiographic stage, increased frequency of lung opacities, reticular shadows, and thickened BVB on HRCT. Stepwise regression analysis showed that chest radiographic stage IV, higher age, smoking, and thickened BVB were independently associated with lower FEV(1)/FVC.The frequency of airflow limitation was 8.8% in Japanese sarcoidosis patients. Chest radiographic stage IV, higher age, smoking, and thickened BVB were associated with airflow limitation in patients with sarcoidosis.

Objective To investigate the frequency of pulmonary hypertension (PH) and clinical parameters associated with PH in sarcoidosis patients. Methods A prospective, observational study was performed on 246 consecutive Japanese sarcoidosis patients followed up at the outpatient sarcoidosis clinic in the Central Clinic of Kyoto. The patients were evaluated for PH by Doppler echocardiography. Among these patients, 192 underwent pulmonary function tests. In addition, high-resolution CT of the lung was evaluated for the presence of lymph node enlargement, lung opacity, and thickening of bronchovascular bundles in 122 patients. PH was defined as estimated systolic pulmonary artery pressure (sPAP) ≥ 40 mm Hg. The frequency of PH was evaluated, and clinical parameters were compared between patients with PH and those without PH. Results Among 212 patients who were successfully evaluated for sPAP, 12 patients (5.7%) had PH. Patients with PH had the following clinical characteristics: advanced chest radiographic stage, decreased oxygen saturation, predominantly male gender, and decreased percentage of predicted vital capacity, percentage of predicted FVC, percentage of predicted FEV 1 , percentage of predicted functional residual capacity, and percentage of predicted total lung capacity (%TLC). Multivariate logistic regression analysis showed that decreased %TLC was independently associated with PH. There was a weak negative correlation between sPAP and %TLC (p Conclusions The frequency of PH in Japanese sarcoidosis patients was 5.7% evaluated with Doppler echocardiography. Decreased lung volume increases the risk of PH developing in patients with sarcoidosis.

Background Although exercise capacity is an important outcome measure in patients with COPD, its longitudinal course has not been analyzed in comparison to the change in pulmonary function. Purpose To examine how exercise capacity would deteriorate over time in patients with COPD, and what factors would contribute to it. Methods A total of 137 male outpatients with moderate-to-very-severe COPD were examined. The average age was 69.0 ± 6.6 years (± SD), and the mean postbronchodilator FEV1 was 45.9 ± 15.4% predicted. Progressive cycle ergometry and pulmonary function testing were performed at entry, and every 6 months thereafter over 5 years. Due to the presence of missing data, a mixed-effect model analysis was then used to estimate the longitudinal changes in various clinical parameters. Results Peak oxygen uptake ( V ˙ o2), peak minute ventilation ( V ˙ e), and peak tidal volume (Vt) during exercise declined significantly over time (p < 0.0001), which was no less rapid than the deterioration in FEV1. The mean decline rates for peak V ˙ o2 were 32 ± 60 mL/min/yr and 0.5 ± 1.0 mL/min/kg/yr. Multiple regression analysis revealed that the changes in peak V ˙ e, peak Vt, and peak respiratory rates were significant predictors for the change in peak V ˙ o2. Conclusion We demonstrated clear evidence of measurable and progressive deterioration in exercise capacity in COPD patients, which was no less rapid than the decline in airflow limitation. Dynamic ventilatory constraints during exercise also deteriorated over time, which most significantly contributed to this exercise capacity deterioration. In addition to pulmonary function, the longitudinal follow-up of exercise capacity is important not to miss the overall deterioration in COPD.

Study objectives: Hypoxemia increases corrected QT dispersion (QTcD), which is the difference between the maximum and minimum QT intervals and is a strong risk factor for cardiovascular mortality. The aim of this study was to investigate the QTcD in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS), and the relationship between the QTcD and 123 I-metaiodobenzylguanidine (MIBG) cardiac imaging, which reflects cardiac sympathetic activity. Setting: A university hospital. Patients: Forty-eight OSAHS patients without cardiac diseases (mean [ SD] age, 45.9 10.8 years; apnea-hypopnea index [AHI] 51.9 18.5 events per hour) who underwent polysomnography before treatment and on the first night of nasal continuous positive airway pressure (nCPAP) treatment. Methods: Before and after nCPAP treatment was started, we measured the QTcD with computer software, before, during, and after sleep, as well as the washout rate of the MIBG administered for cardiac imaging. As a control, QTcD was also measured in the morning from 26 healthy subjects. Results: Before treatment, the mean QTcD during sleep (65.0 14.6 ms) was greater than that before sleep (57.0 13.5 ms; p < 0.0001). Meanwhile, after 1 night of nCPAP therapy, the QTcD during sleep (50.6 11.4 ms) decreased from that before treatment (p < 0.0001) and was smaller than the QTcD before sleep (56.2 13.3 ms; p 0.003). Before treatment, the QTcD during sleep correlated with the AHI (r 0.38; p 0.009) and the percentage of time that SaO2 was < 90% (SaO2 < 90% time) [r 0.34; p 0.018]. The QTcD did not correlate with the body mass index or the washout rate of MIBG. However, the washout rate of MIBG correlated with the AHI and the SaO2 < 90% time. Conclusions: Nocturnal QTcD is increased in OSAHS patients but is decreased by nCPAP therapy independently of cardiac sympathetic function. (CHEST 2004; 125:2107–2114)

Background Investigations using high-resolution CT (HRCT) show that bronchial dilatation (BD) is found in many patients with asthma. However, the pathogenesis and pathophysiologic relevance of BD in asthma are poorly understood. A balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may control the remodeling of extracellular matrix, and excess MMPs have been associated with destruction or dilatation of airways in patients with bronchiectasis. Objectives To study the prevalence of BD as assessed by HRCT according to standard subjective criteria in 37 patients with stable asthma and 10 healthy control subjects, and to examine the relation of BD in asthmatic patients to clinical characteristics and sputum indices, including MMP-9 and TIMP-1 levels. Design A prospective cohort study. Results At least one dilated bronchus was present in 23 asthmatic subjects (62%) and 2 control subjects (20%) [p = 0.030]. The ratio of dilated bronchi to all eligible bronchi in each subject (individual BD%) was higher in the asthmatic patients than in the control subjects (11.4 ± 16.1% vs 1.3 ± 3.0%, p=0.011) [mean ± SD]. Asthmatic patients with (n = 23) and those without BD (n = 14) were similar with regard to age, duration and severity of asthma, atopy, pulmonary function, sputum eosinophil or neutrophil count, and sputum levels of MMP-9 or TIMP-1 and their molar ratio. Individual BD% of asthmatic patients was also unrelated to these clinical and sputum variables. When analysis was confined to the 23 patients with BD, however, individual BD% correlated with the severity score of asthma ( r = 0.49, p=0.023). The results of follow-up HRCT obtained from 19 patients suggested that BD was a fixed rather than transient phenomenon. Conclusion BD is more prevalent in asthmatic patients than in normal subjects and might be associated with the severity of asthma. Cellular inflammation or possible imbalance between MMP-9 and TIMP-1 was not demonstrated in this study to be related to BD in asthma.

Background: The finding that only 15 to 20% of cigarette smokers acquire COPD suggests that there is a genetic predisposition to the disease. Genetic polymorphism of the group-specific component of serum globulin (Gc-globulin), also known as vitamin-D– binding protein, is considered one of the candidates for the susceptibility to COPD. However, the role of Gc-globulin polymorphism in the development of COPD remains inconclusive. Study objectives: To determine whether Gc-globulin gene polymorphism plays a role in the development of COPD in the Japanese population, and whether it is associated with the physiologic deterioration in COPD, and its radiologically detectable correlates. Design: Association study. Subjects and methods: One hundred three patients with COPD and 88 healthy smokers sampled from the Japanese population were genotyped for Gc-globulin by the restriction fragment-length polymorphism method. Based on the results of the genotyping, we investigated the relationship between Gc-globulin polymorphism and a physiologic/radiologic indicator of lung function, namely, the annual decline of FEV1 (dFEV1) in 86 patients with COPD and 21 healthy smokers. Additionally, highresolution CT parameters such as low-attenuation area percentage (LAA%) and average CT number (mean CT score) were measured in 85 patients with COPD. Results: There was an increased proportion of Gc*1F homozygotes in the patients with COPD (32%) compared with the healthy smokers (17%) [p 0.01; odds ratio, 2.3; 95% confidence interval, 1.2 to 4.6]. Patients with COPD and the Gc*1F allele showed a larger dFEV1 (p 0.01), higher frequency with LAA% > 60% (p 0.01), and lower mean CT score than patients without this allele (p 0.03). Conclusion: Gc-globulin polymorphism is significantly associated with susceptibility to COPD, and also with the severity of the disease. (CHEST 2004; 125:63–70)

Asthma and COPD are the most prevalent of lung diseases and contribute an enormous burden of morbidity in North America and globally. In both conditions, inflammation leads to airway remodeling, which contributes to airway narrowing. To date, airway remodeling has only been assessed using histological examination of airways. However, it may now be possible to assess and quantify the extent of airway remodeling in vivo using high-resolution CT (HRCT). The aim of this article is to review the use of HRCT in the investigation of airway remodeling. A number of investigators have reported techniques to make measurements of airway dimensions using CT and an increasing number of quantitative methods are being developed. Using these techniques, airway dimensions have been examined in patients with asthma and COPD. In patients with asthma, the airway wall area was increased without a decrease in luminal area, whereas in patients with COPD, the airway luminal area was decreased and airway wall area was increased. The different pattern of remodeling may reflect fundamental differences in the inflammatory processes in asthma and COPD and could influence the reversibility of the narrowing. It has also been shown that, by quantifying both the extent of emphysema and of airway remodeling, CT is useful in differentiating COPD patients who have primarily parenchymal disease from those who have primarily airway pathology. With additional advances in technology, it is likely that quantitative assessment of airway wall dimensions will ultimately provide a valuable tool for the study of airway disease.

CT scanning allows assessment of airway-wall thickness and is useful for diagnosing and assessing various lung diseases, including asthma and COPD. Several studies have reported that CT scan-estimated dimensions are positively correlated with pulmonary function test results and a positive response to treatment. However, to our knowledge, airway disease complicated by inflammatory bowel disease has not yet been assessed using CT scan-estimated dimensions. A 61-year-old woman with ulcerative colitis (UC) complained of cough, sputum, and fever 4 months after undergoing a total colectomy and rectal mucosectomy. Examination of bronchial biopsy samples demonstrated lymphocytic and plasma cell infiltration of the epithelium and submucosa. CT scan-estimated dimensions indicated thickening of the airways. Chronic bronchitis complicated with UC was diagnosed, and high-dose inhaled corticosteroid therapy was prescribed. Three months later, the CT scan-estimated dimensions of the patient's airways, her symptoms, and pulmonary function test results were dramatically improved.

We developed an automated method to recognize the lung in a computed tomographic (CT) image. With computer-assisted analysis, we were able to describe the continuous low attenuation (less than -960 Hounsfield units) areas (CLA) on chest CT scans. The size (CLAs) and number (CLAn) of the CLA and the percentage of total lung area occupied by low attenuation area (LAA%) were measured using CT scans obtained from 24 patients with chronic pulmonary emphysema (CPE) and 13 control patients. The automated algorithm recognized the lung areas successfully in all patients. The CLAs and LAA% were significantly higher, and CLAn was significantly lower in patients with CPE than in controls. There was a significant correlation between CT parameters and pulmonary function test results. The histograms of the size of CLA could be represented as a power function in each patient. This automated method should be useful in objectively defining the affected areas in the lungs of patients with CPE.

Sputum cell-subtype profiles in cough-variant asthma (CVA) are unknown.Ninety-eight inhaled corticosteroid (ICS)-naive CVA patients were classified according to sputum eosinophil (eos)/neutrophil (neu) counts, as reported in subjects with asthma, as eosinophilic (E) (eos ≥ 1.0%, neu61%; n = 28), neutrophilic (N) (eos1.0%, neu ≥ 61%; n = 31), mixed granulocytic (M) (eos ≥ 1.0%, neu ≥ 61%; n = 12), and paucigranulocytic (P) (eos1.0%, neu61%; n = 27) subtypes. Patient characteristics; sputum levels of eosinophil cationic protein (ECP), IL-8, and neutrophil elastase (NE); and daily ICS doses required to maintain control during follow-up (6, 12, 18, and 24 months) were compared, retrospectively.Subtype N patients, predominantly women, were marginally older than the other subtypes, but FEV(1), airway responsiveness, and total and specific IgE results did not differ. ECP levels were higher in M and E than in N and P subtypes, being similar between M and E or N and P subtypes. Levels of IL-8 and NE were higher in M than in other subtypes, being similar among the latter. ICS doses were initially similar in all subtypes (800 μg equivalent of beclomethasone) but were higher in M than in N and P subtypes throughout follow-up, with E being intermediate between M and N or P subtypes. ICS doses decreased (halved or quartered) in E, N, and P patients followed for 24 months (P.0001 for all) but remained unchanged in M subjects. IL-8 and NE levels correlated positively with ECP levels.In addition to eosinophils, neutrophils, which are possibly activated in the presence of eosinophils, may participate in the pathophysiology of CVA.

Background Emphysematous change as assessed by CT imaging has been reported to correlate with COPD prognostic factors such as FEV 1 and diffusing capacity of the lung for carbon monoxide (D lco ). However, few studies have assessed the relationship between CT scan assessment and COPD mortality from mild to severe stages of the disease. In this study, we analyzed this relationship in patients with various stages of COPD. Methods Two hundred and fifty-one outpatients with stable COPD were included in the study. CT scan and pulmonary function tests were performed at study entry in a single institution. The percentage of low attenuation area was measured to quantitatively evaluate emphysematous change with a custom-made software. Prognostic data also were collected, and the median follow-up time was 8 years. Results Of the 251 patients, 79 died, with 40 classified as respiratory deaths not involving lung cancer. Univariate Cox analysis revealed that emphysematous change as assessed by CT scan, lung function, age, or BMI were significantly correlated with mortality. Multivariate analysis revealed that emphysematous change as assessed by CT scan had the best association with mortality. Conclusions Emphysematous change as assessed by CT scan predicts respiratory mortality in outpatients with various stages of COPD.

Mucus hypersecretion is an important pathophysiologic index of airway disease. Measurement of secreted mucin in sputum has been reported in asthma, but not in chronic cough with or without increased sputum production.We studied 49 patients with classic asthma (CA), 39 with cough-variant asthma (CVA), nine and five with chronic cough associated with sinobronchial syndrome (SBS) and gastroesophageal reflux disease (GERD), respectively, and 11 healthy controls. Seventeen patients with CA, but none from the other groups, were taking antiinflammatory medications. Mucin levels in induced sputum supernatants were measured by enzyme-linked immunosorbent assay, which detects airway mucin, probably including MUC5AC and MUC5B.Mucin levels were higher in patients with CA (674.2 +/- 548.8 microg/mL) and SBS (638.4 +/- 650.7 microg/mL) than in controls (212.0 +/- 167.1 microg/mL) (P = .0037 and .044). They were also higher in patients with CA than in those with CVA (350.4 +/- 374.0 microg/mL) and GERD (134.3 +/- 93.1 microg/mL) (P = .0016 and 0.015), but results did not differ between the latter groups and controls. When the four disease groups were combined, patients with frequent sputum production had greater mucin levels than those with occasional (P = .0023) or no sputum production (P.0001). Patients with CA showed negative correlations of mucin levels with respiratory resistance indices on impulse oscillation and with airway sensitivity to methacholine.Sputum mucin levels differ in various respiratory conditions when compared with controls, primarily reflecting the degree of sputum production. Airway mucin might possibly exert protective effects in asthma, at least between exacerbations, but this issue needs to be further clarified by future studies.

Background It is unclear whether an abnormal swallowing reflex affects COPD exacerbations. This study investigated the prevalence of abnormal swallowing reflexes and its relationship with COPD exacerbation prospectively. We also clarified its association with gastroesophageal reflux disease (GERD) and airway bacterial colonization. Methods Swallowing reflex and serum C-reactive protein (CRP) levels were examined in subjects with stable COPD and in control subjects. Concurrently, GERD symptoms were assessed using a self-reported questionnaire, and sputum bacterial cultures were investigated in the same subjects. Exacerbations were counted prospectively during the following 12 months. Results The study group comprised 67 subjects with COPD and 19 controls. The prevalence of abnormal swallowing reflex was significantly higher in subjects with COPD (22/67) than controls (1/19; P = .02). Among subjects with COPD, the serum CRP level, GERD symptoms, isolation of sputum bacteria, and the frequency of exacerbations were significantly increased in those with abnormal swallowing reflexes compared with controls (2.72 vs 1.04 mg/L, P = .04, for serum CRP level; 6.75 vs 4.10 points, P = .04, for GERD symptoms; 5/11 vs 3/22, P = .04, for the isolation of sputum bacteria; and 2.82 vs 1.56/y, P = .007, for the annual frequency of exacerbations). Multivariable analysis confirmed that abnormal swallowing reflex was significantly associated with frequent exacerbations (≥ 3/y; P = 0.01). Conclusions Abnormal swallowing reflexes frequently occurred in subjects with COPD and predisposed them to exacerbations. Abnormal swallowing reflexes in COPD might be affected by the comorbidity of GERD, and cause bacterial colonization.

Smoking and obesity are leading global causes of death. The aim of the present study was to develop a test to detect early lung abnormalities caused by smoking and/or obesity and to elucidate the underlying mechanisms and major contributory factors.One hundred twenty-nine healthy adults, 20 to 40 years of age, with normal spirometry findings, were divided into the following five groups: 38 healthy subjects (15 female subjects); 46 smokers (5 female smokers); 18 overweight nonsmokers (2 female nonsmokers; normal body mass index [BMI],or= 25 kg/m(2); range, 25.0 to 37.2 kg/m(2)); 19 overweight smokers (1 female smoker; BMI range, 25.2 to 33.5 kg/m(2)); and 8 ex-smokers (BMI range, 20.8 to 24.1 kg/m(2)). A modified pulse oximeter was employed for measuring the fall in pulse oximetric saturation caused by 20-s breath-holding (dSpo(2)) at resting end expiration in the sitting posture.In healthy subjects, dSpo(2) had no significant correlation with age (r(2) = 0.009; p = 0.66). In smokers, dSpo(2) correlated with both the number of pack-years (r(2) = 0.590; p0.001) and closing volume (CV)/vital capacity (VC) ratio (r(2) = 0.573; p0.001). In overweight nonsmokers, dSpo(2) increased significantly with BMI alone (r(2) = 0.667; p0.001). In overweight smokers, the largest increase in the mean dSpo(2) was observed. Multiple linear regression analysis suggested that BMI and CV/VC are the two major contributing factors determining dSpo(2) during breath-holding. In young former smokers, no significant increase in the mean dSpo(2) was observed (p = 0.77) a mean (+/- SD) duration of 5.2 +/- 2.9 years after the cessation of smoking. No significant difference in dSpo(2) was observed between men and women.A new test that measures oxygen saturation during breath-holding reveals early lung abnormalities in subjects who either smoke or are overweight, especially if these factors are combined. Peripheral airway abnormalities and/or lung volume reduction may play roles in the greater desaturation.

Although exercise capacity is an important outcome measure in patients with COPD, its longitudinal course has not been analyzed in comparison to the change in pulmonary function.To examine how exercise capacity would deteriorate over time in patients with COPD, and what factors would contribute to it.A total of 137 male outpatients with moderate-to-very-severe COPD were examined. The average age was 69.0 +/- 6.6 years (+/- SD), and the mean postbronchodilator FEV(1) was 45.9 +/- 15.4% predicted. Progressive cycle ergometry and pulmonary function testing were performed at entry, and every 6 months thereafter over 5 years. Due to the presence of missing data, a mixed-effect model analysis was then used to estimate the longitudinal changes in various clinical parameters.Peak oxygen uptake (Vo(2)), peak minute ventilation (Ve), and peak tidal volume (Vt) during exercise declined significantly over time (p0.0001), which was no less rapid than the deterioration in FEV(1). The mean decline rates for peak Vo(2) were 32 +/- 60 mL/min/yr and 0.5 +/- 1.0 mL/min/kg/yr. Multiple regression analysis revealed that the changes in peak Ve, peak Vt, and peak respiratory rates were significant predictors for the change in peak Vo(2).We demonstrated clear evidence of measurable and progressive deterioration in exercise capacity in COPD patients, which was no less rapid than the decline in airflow limitation. Dynamic ventilatory constraints during exercise also deteriorated over time, which most significantly contributed to this exercise capacity deterioration. In addition to pulmonary function, the longitudinal follow-up of exercise capacity is important not to miss the overall deterioration in COPD.

Investigations using high-resolution CT (HRCT) show that bronchial dilatation (BD) is found in many patients with asthma. However, the pathogenesis and pathophysiologic relevance of BD in asthma are poorly understood. A balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may control the remodeling of extracellular matrix, and excess MMPs have been associated with destruction or dilatation of airways in patients with bronchiectasis.To study the prevalence of BD as assessed by HRCT according to standard subjective criteria in 37 patients with stable asthma and 10 healthy control subjects, and to examine the relation of BD in asthmatic patients to clinical characteristics and sputum indices, including MMP-9 and TIMP-1 levels.A prospective cohort study.At least one dilated bronchus was present in 23 asthmatic subjects (62%) and 2 control subjects (20%) [p = 0.030]. The ratio of dilated bronchi to all eligible bronchi in each subject (individual BD%) was higher in the asthmatic patients than in the control subjects (11.4 +/- 16.1% vs 1.3 +/- 3.0%, p = 0.011) [mean +/- SD]. Asthmatic patients with (n = 23) and those without BD (n = 14) were similar with regard to age, duration and severity of asthma, atopy, pulmonary function, sputum eosinophil or neutrophil count, and sputum levels of MMP-9 or TIMP-1 and their molar ratio. Individual BD% of asthmatic patients was also unrelated to these clinical and sputum variables. When analysis was confined to the 23 patients with BD, however, individual BD% correlated with the severity score of asthma (r = 0.49, p = 0.023). The results of follow-up HRCT obtained from 19 patients suggested that BD was a fixed rather than transient phenomenon.BD is more prevalent in asthmatic patients than in normal subjects and might be associated with the severity of asthma. Cellular inflammation or possible imbalance between MMP-9 and TIMP-1 was not demonstrated in this study to be related to BD in asthma.

Study objectives To assess the optimal cutoff level of breath CO concentration to distinguish actual smokers from nonsmokers among patients with asthma and COPD. Setting Kyoto University Hospital outpatient clinic. Subjects and methods Three hundred thirty-one consecutive outpatients (161 with asthma and 170 with COPD) were examined cross-sectionally by self-reported smoking status, breath CO monitoring, and serum cotinine concentration. Actual smoking status was verified by serum cotinine concentration. Results Mean serum cotinine concentrations of never smokers, former smokers, and current smokers with asthma were 6.0 ± 5.2 ng/mL, 12.1 ± 25.0 ng/mL, and 198.3 ± 181.7 ng/mL, respectively (± SD). Mean serum cotinine concentrations of former smokers and current smokers with COPD were 23.2 ± 69.2 ng/mL and 191.1 ± 109.8 ng/mL, respectively. Mean breath CO levels of never smokers, former smokers, and current smokers with asthma were 6.1 ± 2.4 ppm, 7.7 ± 3.2 ppm, and 19.9 ± 17.3 ppm, respectively. Mean breath CO levels of former smokers and current smokers with COPD were 7.7 ± 4.3 ppm and 13.5 ± 6.5 ppm, respectively. The optimal cutoff level of breath CO to discriminate between actual smokers and nonsmokers was 10 ppm in patients with asthma and 11 ppm in patients with COPD, giving 85.0% and 73.1% sensitivity, and 85.8% and 84.7% specificity, respectively. Conclusion The optimal cutoff level of breath CO to assess actual smoking status was 10 ppm in patients with stable asthma and 11 ppm in patients with stable COPD. In patients with asthma and COPD, breath CO levels were potentially influenced by underlying airway inflammation, suggesting misclassification in the assessment of smoking status by breath CO.

Asthma and COPD are the most prevalent of lung diseases and contribute an enormous burden of morbidity in North America and globally. In both conditions, inflammation leads to airway remodeling, which contributes to airway narrowing. To date, airway remodeling has only been assessed using histological examination of airways. However, it may now be possible to assess and quantify the extent of airway remodeling in vivo using high-resolution CT (HRCT). The aim of this article is to review the use of HRCT in the investigation of airway remodeling. A number of investigators have reported techniques to make measurements of airway dimensions using CT and an increasing number of quantitative methods are being developed. Using these techniques, airway dimensions have been examined in patients with asthma and COPD. In patients with asthma, the airway wall area was increased without a decrease in luminal area, whereas in patients with COPD, the airway luminal area was decreased and airway wall area was increased. The different pattern of remodeling may reflect fundamental differences in the inflammatory processes in asthma and COPD and could influence the reversibility of the narrowing. It has also been shown that, by quantifying both the extent of emphysema and of airway remodeling, CT is useful in differentiating COPD patients who have primarily parenchymal disease from those who have primarily airway pathology. With additional advances in technology, it is likely that quantitative assessment of airway wall dimensions will ultimately provide a valuable tool for the study of airway disease.

Background: Disease-specific health status measures are characterized by higher responsiveness than generic measures and may be preferred in clinical trials. However, comparisons of responsiveness between various disease-specific measures have rarely been performed in asthma studies. Study objective: We investigated and compared the responsiveness of health status scores in asthmatic patients during treatment using three different disease-specific measures: the Juniper Asthma Quality of Life Questionnaire (AQLQ), the Living with Asthma Questionnaire (LWAQ), and the Airways Questionnaire 20 (AQ20). Methods: We attempted to follow up 170 patients with newly diagnosed asthma over a 6-month period. Patients underwent treatment with inhaled corticosteroids in accordance with the guideline. A health status evaluation using three disease-specific measures, and pulmonary function tests were performed on the initial visit, and at 3 months and 6 months. The effect size and the standardized response mean were used as responsiveness indexes. Results: A total of 109 patients completed the 6-month follow-up and were then analyzed. All health status scores and FEV1 measures improved during the first 3 months (p < 0.001). The total of the AQLQ scores showed high responsiveness indexes ranging from 1.28 to 1.46 between baseline and 3 months, and baseline and 6 months. Spearman correlation coefficients were smaller between the change in FEV1 and the change in the LWAQ. Although the AQ20 also demonstrated high responsiveness, a ceiling effect was indicated. Conclusions: The AQLQ was the most responsive measure during asthma treatment. The relationship between the change in airflow limitation and the change in the LWAQ was weaker compared to the AQLQ and the AQ20. Although the AQ20 was also responsive and its simplicity is favorable, the ceiling effect should be considered when using it. (CHEST 2002; 122:1228 –1233)

Background: The benefits of inhaled corticosteroids in the management of COPD are less apparent than they are in asthma therapy, and the potential for adverse systemic effects of high-dose inhaled corticosteroids has been recognized recently. It is therefore essential to know the maximal obtainable benefits in order to assess the risk/benefit ratio of this treatment. Purpose: The aim of this study was to investigate the maximal obtainable benefits of high-dose inhaled corticosteroids, 3 mg/d of beclomethasone dipropionate (BDP), when used in combination with adequate doses of regular bronchodilators in patients with stable COPD. Study Design: Thirty patients with stable COPD completed a randomized, double-blind, placebocontrolled cross-over trial with either 3 mg/d of BDP or with a matching placebo using a metered-dose inhaler with a spacer device for 4 weeks during each treatment period. All of the patients continued to inhale both 400 mg of salbutamol qid and 80 mg of ipratropium bromide qid. Results: The mean prebronchodilator FEV1 was 0.97 6 0.35 L during the placebo period and 1.08 6 0.38 L during the BDP period (p < 0.001). While on BDP, five patients demonstrated a response in their FEV1 of more than 8.5% of the predicted value, which was above the range that covered 95% of the distribution of the placebo response. The mean absolute improvement in the FEV1 in these 5 objective responders was 0.34 6 0.10 L, compared to 0.06 6 0.09 L in the 25 objective nonresponders. Symptom scores for wheezing and dyspnea were significantly better with BDP than with placebo. Hoarseness and sore throat were associated more with BDP treatment. Conclusion: Although a considerable minority of patients benefited substantially from this treatment, the overall outcome does not seem to justify the widespread use of this treatment in the light of increasing recognition of the potential adverse systemic effects of high-dose inhaled corticosteroids. (CHEST 1999; 115:31‐37)

Study objectives To investigate the etiology of posthyperventilation (post-HV) hypoxemia following voluntary hyperventilation (VHV), we examined the effects of hypocapnic (hypo-CO 2 ) and isocapnic (iso-CO 2 ) VHV on the hypoxic ventilatory response (O 2 -response) and on the sensation of breathlessness during the O 2 -response. Methods O 2 -responses and visual analog scale (VAS) scores for estimating breathlessness in 10 normal subjects during the O 2 -response under iso-CO 2 conditions and under hypo-CO 2 conditions immediately following voluntary maximal HV of 3 min duration were examined. Results Although there was no significant difference in the post-HV ventilation levels following hypo-CO 2 vs iso-CO 2 VHV, the VAS scores at the start of the O 2 -response following hypo-CO 2 VHV (30.2±24.2 mm) were significantly higher (p 2 -response following iso-CO 2 VHV (13.7±8.4 mm). However, VHV did not have a significant effect on the O 2 -response at 2 min after the VHV when the arterial O 2 saturation (SaO 2 ) was below 90%. The nonsteady-state hypo-CO 2 induced by VHV greatly attenuated the O 2 -response below 90% SaO 2 and VAS scores at 70% SaO 2 . Conclusions Elevated VAS scores immediately following the hypo-CO 2 VHV, which might be independent of actual breathing levels, and the attenuation of the O 2 -response following the hypo-CO 2 VHV were not due to input from lung and chest wall mechanoreceptors induced by the hyperpnea itself, but rather to the hypo-CO 2 induced by hyperpnea.

Study objective To determine the physiologic factors that influence the health-related quality of life (HRQL) in patients with stable COPD and to identify the factors that most influence HRQL. Methods The Nottingham Health Profile (NHP) was used as a general HRQL measure and the Chronic Respiratory Disease Questionnaire (CRQ) was used as a disease-specific HRQL measure to investigate 132 patients with stable COPD, and measurements of HRQL were compared with physiologic measures. Results Vital capacity, FEV 1 , the ratio of the FEV 1 to the FVC, diffusion capacity for carbon monoxide, diffusion capacity corrected for alveolar volume, lifetime cigarette consumption expressed as pack-years, and age were weakly correlated with several dimensions of both the NHP and the CRQ. Factor analysis reduced these variables to three factors. Two factors mainly referring to airflow limitation and diffusing capacity were weakly correlated with several dimensions of both the NHP and the CRQ. Logistic regression analysis identified 4 independent predictors of HRQL: airflow limitation (odds ratio [OR]=0.59 to 0.69), diffusing capacity (OR=0.75 to 0.82), pack-years (OR=1.20 to 1.23), and age (OR=2.13). The CRQ was more sensitive to impairment of HRQL than the NHP. Conclusions The HRQL of patients with stable COPD is partly determined by airflow limitation, diffusing capacity, pack-years, and age. However, these factors could not predict the whole spectrum of HRQL, and the contribution of these factors to HRQL was limited. Therefore, HRQL should be measured directly in addition to physiologic measures.