Preoperative use of inhaled tiotropium in lung cancer patients with untreated COPD

Background and objective:   Lung cancer patients with COPD are at high risk during surgery. Tiotropium, a long-acting bronchodilator, is a preferred maintenance therapy for COPD, but its efficacy in the perioperative period has not been clarified.
Methods:   A retrospective review was performed of the medical records of 102 patients with primary lung cancer and COPD, who underwent scheduled surgery. Twenty-one lung cancer patients with untreated mild-to-severe COPD received tiotropium preoperatively. Spirometry was performed prior to and after 2 weeks of treatment with tiotropium, and at 3 months after surgery.
Results:   Two-week preoperative treatment with tiotropium significantly improved respiratory symptoms and pulmonary function as reflected by FVC (median 3.43 L pretreatment vs 3.52 L post-treatment), FEV₁ (median 2.06 L vs 2.32 L) and FEV₁% (73.2% vs 81.0%) (all P  < 0.001). Postoperative FEV₁% was significantly increased from a median of 56.0% (interquartile range 51.6–60.3) to 63.4% (60.8–66.0) ( P  < 0.001). The increase in FEV₁ was inversely associated with severity of COPD ( r  = −0.59, P  < 0.005). Lung resections were successfully accomplished without complications. The postoperative FEV₁ predicted prior to tiotropium treatment was underestimated (median predicted postoperative FEV₁ 1.65 L vs median measured postoperative FEV₁ 1.96 L, P  < 0.001).
Conclusions:   Preoperative treatment with tiotropium may facilitate surgical treatment for lung cancer patients with COPD. This is encouraging for COPD patients who may require curative lung resections.     

Air trapping: The major factor limiting diaphragm mobility in chronic obstructive pulmonary disease patients

Background and objective:   Patients with COPD can have impaired diaphragm mechanics. A new method of assessing the mobility of the diaphragm, using ultrasound, has recently been validated. This study evaluated the relationship between pulmonary function and diaphragm mobility, as well as that between respiratory muscle strength and diaphragm mobility, in COPD patients.
Methods:   COPD patients with pulmonary hyperinflation ( n  = 54) and healthy subjects ( n  = 20) were studied. Patients were tested for pulmonary function, maximal respiratory pressures and diaphragm mobility using ultrasound to measure the craniocaudal displacement of the left branch of the portal vein.
Results:   COPD patients had less diaphragm mobility than did healthy individuals (36.5 ± 10.9 mm vs 46.3 ± 9.5 mm, P  = 0.001). In COPD patients, diaphragm mobility correlated strongly with pulmonary function parameters that quantify air trapping (RV: r  = −0.60, P  < 0.001; RV/TLC: r  = −0.76, P  < 0.001), moderately with airway obstruction (FEV₁: r  = 0.55, P  < 0.001; airway resistance: r  = −0.32, P  = 0.02) and weakly with pulmonary hyperinflation (TLC: r  = −0.28, P  = 0.04). No relationship was observed between diaphragm mobility and respiratory muscle strength (maximal inspiratory pressure: r  = −0.11, P  = 0.43; maximal expiratory pressure: r  = 0.03, P  = 0.80).
Conclusion:   The results of this study suggest that the reduction in diaphragm mobility in COPD patients is mainly due to air trapping and is not influenced by respiratory muscle strength or pulmonary hyperinflation.     

The utility of the chest radiograph in diagnosing exacerbations of pulmonary sarcoidosis

Background and objective:   To quantify the CXR using a profusion of small lung opacities score in patients with pulmonary exacerbation of sarcoidosis. In particular, the study sought to determine whether the CXR changes were a reliable indicator of disease exacerbation.
Methods:   The study recruited patients with an exacerbation of pulmonary sarcoidosis, who were attending a university medical centre sarcoidosis clinic. Pulmonary exacerbation was defined as worsening pulmonary symptoms, thought to be related to sarcoidosis, that responded to an increase in corticosteroid dose. A subset of patients were identified who met the criteria of spirometric decline of ≥10% in FVC or FEV₁ from the previous (baseline) visit. Patients required a baseline CXR and spirometry and had CXR and spirometry performed at the initial assessment. Two International Labour Organisation B readers interpreted the CXR in a blinded manner.
Results:   All study patients ( n  = 36) were African American; there were 24 patients in the 'spirometric decline' subgroup. Agreement between the B readers was moderate (kappa = 0.54, P  < 0.01). The mean profusion score increased, or worsened by 1.38 points (SD = 3.60, P  = 0.008) for the exacerbation group while the 'spirometric decline' group worsened by an average of 1.80 points (SD = 3.81, P  = 0.031). There was too much variation for a cut-off to be identified that would reliably diagnose exacerbations. There was no significant correlation between FVC or FEV₁ and profusion score.
Conclusions:   The CXR International Labour Organisation profusion score is not a reliable test to detect pulmonary exacerbations of sarcoidosis. However, a CXR may be useful to exclude other diagnostic possibilities.     

Association between CRHR1 polymorphism and improved lung function in response to inhaled corticosteroid in patients with COPD

Background and objective:   Inhaled corticosteroids are used to treat COPD and asthma. An association between sequence variants in the corticotrophin-releasing hormone receptor 1 ( CRHR1 ) gene and improved lung function in asthmatics treated with inhaled corticosteroids was reported recently. This study investigated the association between the change in lung function in response to inhaled corticosteroids and single-nucleotide CRHR1 polymorphisms in patients with COPD.
Methods:   COPD patients ( n  = 87) with a positive smoking history were recruited from the pulmonary clinics of 11 hospitals in Korea. Patients were treated with fluticasone propionate and salmeterol for 12 weeks and lung function was measured at baseline and after the 12-week treatment. Eighty-four of the 87 subjects were successfully genotyped.
Results:   Seventy-one patients with the wild-type GG genotype and 13 patients with the heterozygous GT genotype in rs242 941 were evaluated. After 12-week treatment, the change in FEV₁ was significantly higher in patients with wild-type GG genotype (6.0 ± 0.8% of predicted FEV₁) than in GT heterozygotes (−0.8 ± 1.8, P  = 0.003).
Conclusions:   Improved FEV₁ following inhaled corticosteroid and a long-acting β2-agonist was associated with CRHR1 genetic polymorphism in patients with COPD.     

Non-invasive ventilation improves peripheral oxygen saturation and reduces fatigability of quadriceps in patients with COPD

Background and objective:   Non-invasive ventilation (NIV) might improve peripheral muscle function and exercise capacity in severely disabled patients. This study evaluated the physiological impact of NIV on isokinetic concentric strength and endurance of lower limb muscles in patients with severe COPD.
Methods:   This clinical trial tested COPD patients ( n  = 24) and healthy subjects ( n  = 18). Subjects underwent isokinetic dynamometry tests while given either bi-level positive airway pressure ventilation (BV) or sham ventilation (SV), in a randomized order with 30 min of rest prior to each intervention. The inspiratory level of BV was set up to 14 cm H₂O and expiratory pressure up to 6 cm H₂O. Peripheral oxygen saturation (SpO₂), heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP) at the peak of exercise were measured for each intervention.
Results:   Compared with controls, COPD patients had lower values of SpO₂ and HR ( P  < 0.01) during both BV and SV and lower values of DBP ( P  < 0.01) during BV. BV improved SpO₂ ( P  < 0.01), and reduced SBP in both COPD ( P  < 0.01) and control groups ( P  < 0.05) and reduced DBP in COPD patients ( P  < 0.01). BV also reduced the fatigue index in COPD patients when compared with SV ( P  = 0.003). Variation (BV-SV) of total work at the peak of the test was higher in the control group than in the COPD group ( P  < 0.05).
Conclusions:   BV improved SpO₂ and reduced the fatigability of the quadriceps muscle in patients with severe COPD. These results support the need for further evaluation of BV as adjunct during high-intensity strength exercise training in these patients.     

Non-invasive ventilation during arm exercise and ground walking in patients with chronic hypercapnic respiratory failure

Background and objective:   People with chronic hypercapnic respiratory failure (HRF) often have a ventilatory limitation to exercise with difficulty performing activities of daily living. Although non-invasive ventilation (NIV) appears to reduce the ventilatory limitation and improve exercise performance in people with severe COPD, the effect of NIV during functional activities such as unsupported arm exercise (UAE) and ground walking in people with chronic HRF is unclear.
Methods:   Seventeen patients with chronic HRF (PaCO₂ 52.1 ± 5.3 mm Hg) performed a series of UAE tests, and 15 patients (PaCO₂ 51.7 ± 3.8 mm Hg) performed a series of endurance shuttle walk tests, with and without NIV in a randomized cross-over design.
Results:   NIV during UAE increased endurance time by a mean of 91 s (95% confidence interval (CI): 10–172, P  = 0.031) and reduced dyspnoea by a mean of 2.3 on the Borg scale (95% CI: 1.0–3.7, P  = 0.002) compared with exercise without NIV. There was a non-significant increase in walking endurance time with NIV during exercise (119 s, 95% CI: −17 to 254, P  = 0.081); however, isotime dyspnoea was unchanged compared with walking without NIV (−1.0, 95% CI: −3.0 to 1.0, P  = 0.29).
Conclusion:   NIV during UAE increased endurance time and reduced dyspnoea compared with exercise without NIV in patients with chronic HRF. Investigation of the role of NIV as an adjunct to UAE training is warranted. In contrast, NIV during ground walking did not improve exercise capacity. However, the pressure support provided may have been inadequate as dyspnoea was not reduced.     

Association of beta-2-adrenoceptor polymorphisms and pulmonary function in patients with chronic obstructive pulmonary disease

Aims:   The Dutch Hypothesis suggests that asthma and chronic obstructive pulmonary disease may share some pathogenic mechanisms. There is considerable evidence that polymorphisms of the β₂ adrenoceptor have disease-modifying roles in juvenile onset asthma, determining severity and response to β agonists, but not determining disease susceptibility. There is evidence from family and twin studies to suggest that chronic obstructive pulmonary disease (COPD) also has a significant genetic component. We therefore hypothesized that β₂ adrenoceptor polymorphisms would have similar disease modifying roles in patients with COPD.
Methods:   One hundred and ninety-five COPD subjects and 142 matched controls were recruited. All had detailed clinical phenotyping. Subjects were genotyped for the Agr → Gly polymorphism at codon 16, the Gln → Glu polymorphism at codon 27, and the SNPC/T-47 promoter polymorphism.
Results:   In patients with COPD (mean age 67, 57% male), individuals with the homozygous Gly16/homozygous Glu27/homozygous SNP −47*C genotype had significantly worse lung function as measured by forced expiratory volume 1, expressed as a percentage of its predicted value (39.2 compared with 45.8, P  = 0.004), and for forced vital capacity (FVC) percent predicted (77.2 compared with 70.4, P  = 0.02). The polymorphisms had no effect on disease susceptibility.
Conclusion:   The Arg16, Gln27, SNPC/T-47 β₂ adrenoceptor polymorphisms may have disease modifying roles in patients with COPD.     

Longitudinal study of airway dimensions in chronic obstructive pulmonary disease using computed tomography

Background and objective:   Chest CT has been widely used for the evaluation of structural changes in lung parenchyma and airways in cross-sectional studies. There has been no report on the annual changes in airway dimensions as assessed by CT in COPD patients. The objective of this study was to investigate the annual changes in airway dimensions and lung attenuation using CT in patients with COPD and to evaluate the correlations among annual changes in CT measurements and pulmonary function.
Methods:   Eighty-three men with COPD had completed five annual assessments of CT scans and pulmonary function tests over 4 years. Airway dimensions of the basal segment bronchi and lung attenuation on CT images were analysed in 38 subjects in whom the same airway could be measured at least three times, including at entry and at the end of the study.
Results:   Mean annual decline in FEV₁ was 21 mL/year. Annual changes in the percentage of low attenuation areas were not significantly correlated with decline in FEV₁. On the other hand, annual changes in the percentage of wall area (WA%/year) were significantly inversely correlated with annual changes in FEV₁ ( r  = −0.363, P  = 0.025), whereas WA%/year did not differ among severity stages at entry and did not correlate with baseline FEV₁.
Conclusions:   The results showing that annual changes in airway thickening correlated with annual decline in air flow limitation suggests the importance of treatment of airway inflammation in COPD. CT is a useful tool for quantitative estimation not only of emphysema but also of airway lesions in longitudinal studies.     

Non-invasive model predicting clinically-significant portal hypertension in patients with advanced fibrosis

Background and Aims:  Hepatic venous pressure gradient (HVPG) has been established as a predictor for the development of varices, clinical decompensation and death. In the present study, the primary objectives were to determine the diagnostic accuracy of the model developed by using readily-available data in predicting the presence of significant portal hypertension and esophageal varices.
Methods:  This study included a total of 61 consecutive treatment-naive patients with advanced fibrosis (METAVIR F3, F4), established by liver biopsy. All patients underwent subsequent HVPG measurement and upper gastrointestinal endoscopy within 1 week of liver biopsy.
Results:  Seventeen patients (F3, 2/26; F4, 15/35) had clinically-significant portal hypertension (HVPG ≥ 10 mmHg). The Risk Score for predicting significant portal hypertension was 14.2 − 7.1 × log₁₀ (platelet [10⁹/L]) + 4.2 × log₁₀ (bilirubin [mg/dL]). The area under the receiver–operator curve (AUC) curve was 0.91 (95% confidence interval [CI], 0.84–0.98). The optimized cut-off value (Risk Score = −1.0) offered a sensitivity of 88% (95% CI, 62–98%) and a specificity of 86% (95% CI, 72–94%). The AUC of the Risk Score in predicting varices was 0.82 (95% CI, 0.67–0.98). The cut-off had a sensitivity of 82% (95% CI, 48–97%) and a specificity of 76% (95% CI, 62–86%).
Conclusion:  A predictive model that uses readily-available laboratory results may reliably identify advanced fibrosis patients with clinically-significant portal hypertension as well as esophageal varices. However, before accepted, the results of the current study certainly should be validated in larger prospective cohorts.     

Acidosis and raised norepinephrine levels are associated with exercise dyspnoea in idiopathic pulmonary fibrosis

Background and objective:   Exertional dyspnoea limits patients with IPF in their activities of daily living. The mechanism, however, has not been elucidated. This study tested the hypothesis in IPF that exertional dyspnoea correlates with cardiopulmonary exercise responses, specifically changes in arterial blood pH and plasma norepinephrine (NE).
Methods:   Cardiopulmonary exercise testing with measurements of dyspnoea (Borg scale), plasma NE, plasma lactate and arterial blood gases were performed in 29 patients with IPF and in nine controls.
Results:   Both groups showed obvious break points in dyspnoea changes during exercise. In IPF, an abrupt change in the Borg scale, pH, PaCO₂ and plasma NE occurred in the late exercise phase after the 'break point'. Compared with controls, patients with IPF had significantly higher HCO₃^- levels and physiologic dead space/tidal volume during exercise. In IPF, during both exercise phases, the dyspnoea slope (ΔBorg scale/Δminute ventilation) correlated with the pH slope (ΔpH/Δoxygen uptake) (before the break point: r  = −0.537, P  = 0.0022; r  = −0.886, P  < 0.0001, after the break point) and the NE slope (ΔNE/Δoxygen uptake) (before the break point: r  = 0.481, P  = 0.0075; R  = 0.784, P  < 0.0001, after the break point).
Conclusions:   In patients with IPF, exercise-induced acidosis and increases in circulating NE levels were associated with intensity of exertional dyspnoea.     

Protein malnutrition in elderly patients with chronic obstructive pulmonary disease

Background: It has been suggested that hypermetabolism or reduction of total caloric intake or a combination of both conditions occur in malnourished patients with chronic obstructive pulmonary disease (COPD). It is hypothesized that protein malnutrition plays a role in the metabolism of malnourished elderly COPD patients.
Methods: Thirteen COPD patients (mean age: 75.7 years) with severe obstructive ventilatory disorder were divided into two groups: body mass index greater than 20 (group N; n  = 8) and less than 20 (group L; n  = 5). A nutritional survey and metabolic study were performed.
Results: Energy balances appeared more highly positive in group L than in group N and serum concentrations of total protein, albumin and transferrin tended to be lower in group L than in group N (all showed no statistically significant difference). The mean protein digestibility did not show any significant difference between the two groups, suggesting that group L subjects digested and absorbed the ingested dietary protein normally. Mean nitrogen balance was more highly positive in group L than in group N. The FEV₁ decreased significantly with increases in the basal metabolic rate (BMR), total daily energy expenditure and urinary nitrogen excretion, respectively (all P  < 0.05). PaO₂ was positively and significantly correlated with serum concentrations of albumin and transferrin ( P  = 0.001 and P  < 0.05), respectively. Body mass index (BMI) was negatively correlated with BMR ( P  < 0.05).
Conclusions: It is suggested that malnourished COPD patients with lower BMI showed enhanced protein and energy metabolism. Thus, it is likely that malnourished elderly COPD patients could improve through not only supplementation of total carolic intake but also sufficient protein intake.     

Pulmonary gas exchange in the morbidly obese

The literature on pulmonary gas exchange at rest, during exercise, and with weight loss in the morbidly obese (body mass index or BMI ≥ 40 kg m⁻²) is reviewed. Forty-one studies were found (768 subjects weighted mean = 40 years old, BMI = 48 kg m⁻²). The alveolar-to-arterial oxygen partial pressure difference (AaDO₂) was large at rest in upright subjects at sea level (23, range 5–38 mmHg) while the arterial pressure of oxygen (PaO₂) was low (81, range 50–95 mmHg). Arterial pressure of carbon dioxide (PaCO₂) was normal. At peak exercise (162 W), gas exchange improves. Weight loss of 45 kg (BMI = −13 kg m⁻²) over 18 months is associated with an improvement in PaO₂ (by 10 mmHg, range 1–23 mmHg), a reduction in AaDO₂ (by 8 mmHg, range −3 to −16 mmHg), and PaCO₂ (by −3 mmHg, range 3 to −14 mmHg) at rest. Every 5–6 kg reduction in weight increases PaO₂ by 1 and reduces AaDO₂ by 1 mmHg, respectively. Morbidly obese women have better gas exchange at rest compared with morbidly obese men which is likely due to lower waist-to-hip ratios in women than from differences in weight or BMI.     

The effectiveness of a bronchial drainage technique (ELTGOL) in COPD exacerbations

Background and objective:   Exacerbations of COPD are often characterized by increased mucus production that is difficult to treat and worsens patients' outcome. This study evaluated the efficacy of a chest physiotherapy technique (expiration with the glottis open in the lateral posture, ELTGOL) during acute exacerbations of COPD using as outcome measures sputum volume, length of hospitalization, reduction in dyspnoea (Borg score), improvement in quality of life (assessed by the St George Respiratory Questionnaire) and incidence of COPD exacerbations during follow up.
Methods:   The study recruited 59 patients hospitalized for the treatment of acute exacerbation of COPD, who were randomly assigned to a control group and an intervention group. The control group was treated with standard medical therapy while the intervention group was treated with ELTGOL plus medical therapy. A subgroup of patients was followed for 6 months to verify the effects on COPD exacerbations and need for hospitalizations.
Results:   At the time of hospital discharge there was no significant difference between the two groups in the outcome measures, with the exception of the Borg score, which was significantly improved in the ELTGOL group (4.3 ± 1.5 in the control group vs 3.0 ± 1.8 in the ELTGOL group, P  = 0.004). After 6 months there was no significant difference in the other measured parameters between a subset of the groups available for follow up. During follow up, the ELTGOL group had numerically fewer exacerbations and less need for hospitalization though differences were not statistically significant.
Conclusions:   Chest physiotherapy using the ELTGOL technique has a limited role in patients with mild exacerbation of moderate to severe COPD with a tendency towards fewer exacerbations and hospitalizations.     

Lipohypertrophy: does it matter in daily life? A study using a continuous glucose monitoring system

Aims:  To use continuous glucose monitoring (CGMS) to compare glucose profiles in people with type 1 diabetes following injection of insulin into an area affected by lipohypertrophy vs. an area not affected by lipohypertrophy.
Methods:  Eight patients with type 1 diabetes underwent 72 h of CGMS while following a standardized diet and injecting all insulin either into an area with or without lipohypertrophy. Patients underwent two testing periods in random order, separated by 4 days. On day 1 of each test subjects were admitted for measurement of insulin and plasma glucose levels immediately prior to, and hourly for 4 h following, a standardized lunch.
Results:  Insulin area under the curve (AUC)_{0–4 h} was similar for both test periods; 656; interquartile range (IQR): 518–1755 (normal tissue) vs. 602; IQR: 382–1436 (lipohypertrophic tissue), z  = 1.7, p = 0.09. There was also no difference in the median time to maximal insulin concentration (Time_max 2 h; IQR: 2–3 h; z  = 0.6; p = 0.6). There was a 37.5% increase in mean plasma glucose levels following a standardized meal; however this was not significant between sites (AUC_{0–4 h} t  = −1.7; p = 0.1). Moreover, there was no difference in CGMS profiles (AUC_{1–72 h} t  = −0.9; p = 0.4) across the 72-h monitoring period. Overall the prevalence of hypoglycaemia (CGMS readings < 4 mmol/l) was similar between injection sites (11.6 vs. 10.6%, p = 0.1).
Conclusion:  The pharmacokinetic and pharmacodynamic effect of injecting into lipohypertrophic tissue is small in comparison to the usual clinical variation observed with insulin injections.     

Acute effects of hyperoxia on resting pattern of ventilation and dyspnoea in COPD

Background and objective:   Hyperoxia has been shown to reduce resting ventilation, hyperinflation and dyspnoea in patients with severely hypoxaemic COPD. This study assessed the effects of hyperoxia on these resting measures in patients with COPD of varying disease severity and characterized those patients who responded.
Methods:   Measurements of dyspnoea (Borg score), oxyhaemoglobin saturation (SpO₂), inspiratory capacity (IC), minute ventilation, tidal volume, breathing and cardiac frequency were performed at rest in 51 patients with COPD while they breathed air and 44% oxygen, in a randomized double-blinded fashion.
Results:   Hyperoxia induced significant reductions in cardiac frequency and dyspnoea and a significant increase in SpO₂. No significant change was noted in IC for the group overall, and there was substantial inter-subject variation in this measurement. No significant changes were found in ventilation, and there was no correlation between change in dyspnoea and change in IC. In patients with moderate to severe airflow obstruction (FEV₁ < 70% predicted), a significant association was found between the degree of airflow obstruction and change in IC induced by hyperoxia.
Conclusions:   Hyperoxia improved dyspnoea but did not significantly alter resting pulmonary hyperinflation in a group of patients with COPD of varying severity. However, in a subset patients with moderate to severe airflow obstruction a relationship existed between the severity of airflow obstruction and volume response to hyperoxia.     

Procalcitonin as a prognostic factor in severe acute exacerbation of chronic obstructive pulmonary disease

Background and objective:   Little is known about the value of procalcitonin in predicting mortality in patients with an exacerbation of COPD. This study evaluated the clinical and biological predictors of intensive care unit (ICU) mortality in patients with a severe acute exacerbation of COPD.
Methods:   A prospective observational cohort study was conducted of consecutive patients with severe acute exacerbation of COPD requiring intubation and mechanical ventilation. At ICU admission, data were collected on the patients' clinical condition, blood leukocyte count, C-reactive protein and procalcitonin. Cox proportional hazards model was used to determine the risk factors for ICU mortality.
Results:   One hundred and sixteen patients were included in this study. Mean age was 67 years. The mean simplified acute physiology score was 43. Sixty-five per cent of study patients had chronic respiratory insufficiency. Bacteria were cultured at levels considered significant in 36% of study patients. Logistic organ dysfunction score (hazard ratio (95% CI) = 1.19 (1.03–1.37), P  = 0.013), rapidly fatal underlying disease (3.33 (1.40–7.87), P  = 0.003) and procalcitonin level (1.01 (1–1.03), P  = 0.018) were independently associated with increased risk for ICU mortality. Non-invasive mechanical ventilation use before intubation was independently associated with reduced risk for ICU mortality (0.34 (0.14–0.84), P  = 0.020).
Conclusions:   In patients with severe acute exacerbation of COPD requiring intubation and mechanical ventilation, logistic organ dysfunction score, rapidly fatal underlying disease and procalcitonin are independently associated with increased risk for ICU mortality. Non-invasive mechanical ventilation use before intubation was independently associated with reduced risk for ICU mortality.     

A Randomized, Single-Blind Study of Lansoprazole for the Prevention of Exacerbations of Chronic Obstructive Pulmonary Disease in Older Patients

OBJECTIVES: To investigate whether proton pump inhibitor (PPI) therapy reduces the frequency of common colds and exacerbations in patients with chronic obstructive pulmonary disease (COPD).
DESIGN: Twelve-month, randomized, observer-blind, controlled trial.
SETTING: A university hospital and three city hospitals in Miyagi prefecture in Japan.
PARTICIPANTS: One hundred patients with COPD (mean age ± SD 74.9 ± 8.2) participated. They were all ex-smokers and had received conventional therapies for COPD, including smoking cessation and bronchodilators. Patients with gastroesophageal reflux disease or gastroduodenal ulcer were excluded.
INTERVENTION: Patients were randomly assigned to conventional therapies (control group) or conventional therapies plus PPI (lansoprazole 15 mg/d; PPI group) and observed for 12 months.
MEASUREMENTS: Frequency of common colds and COPD exacerbations.
RESULTS: The number of exacerbations per person in a year in the PPI group was significantly lower than that in the control group (0.34 ± 0.72 vs 1.18 ± 1.40; P <.001). The adjusted odds ratio with logistic regression for having exacerbation (≥once/year) in the PPI group compared with the control group was 0.23 ( P =.004). In contrast, there was no significant difference in the numbers of common colds per person per year between the PPI group and the control group (1.22 ± 2.09 vs 2.04 ± 3.07; P =.12). PPI therapy significantly reduced the risk of catching frequent common colds (≥3 times/year), the adjusted odds ratio of which was 0.28 ( P =.048).
CONCLUSION: In this single-blind, nonplacebo-controlled trial, lansoprazole was associated with a significant decrease in COPD exacerbations. More definitive clinical trials are warranted.     

Airway responses to salbutamol after exposure to chemical warfare

Background and objectives:   Increased airway responsiveness to β-agonists is noted in asthmatics and smokers. The lung may be exposed to chemical warfare agents such as mustard gas and pulmonary complications of exposure range from no effect to severe bronchial stenosis. There is little understanding of airway hyperresponsiveness to β-agonist drugs in chemical war victims and this study examined airway responsiveness to salbutamol in victims of chemical warfare.
Methods:   The threshold concentrations of inhaled salbutamol required for a 20% change in FEV₁ as PC₂₀, or a 35% change in specific airway conductance (sGaw) as PC₃₅ were measured in 22 persons exposed to chemical warfare and 15 normal control subjects.
Results:   In 11 of the 22 subjects PC₂₀ salbutamol could be measured and in 15 of the 22 subjects PC₃₅ salbutamol could be measured. This group of patients was the responder group (PC₂₀ = 10.79 and PC₃₅ = 8.55 mg/L) and in them the concentration of salbutamol needed for a response was significantly lower than that required in normal controls (PC₂₀ = 237.68 and PC₃₅ = 88.72 mg/L, P  < 0.001). There was a significant correlation between FEV₁ and PC₂₀ salbutamol ( r  = 0.815, P  < 0.001).
Conclusions:   These results showed increased airway responsiveness to salbutamol in most subjects exposed to chemical warfare; this was correlated with airway calibre.     

Association between angiotensin-converting enzyme gene polymorphisms and exercise performance in patients with COPD

Background and objective:   Recent studies have shown that polymorphisms of the angiotensin-converting enzyme (ACE) gene are closely associated with pulmonary disorders. The ACE gene is involved in the regulation of inflammatory reactions to lung injury, respiratory drive, erythropoiesis and tissue oxygenation. The hypothesis for this study was that the ACE gene may be associated with the ventilatory response to exercise and the aerobic work efficiency of skeletal muscle in patients with COPD.
Methods:   Sixty-one Chinese Han COPD patients and 57 healthy control subjects performed incremental cardiopulmonary exercise testing on a cycle ergometer. ACE genotypes were determined using PCR amplification.
Results:   Resting lung function and blood gas index were not significantly different among the three ACE genotype COPD groups. Similarly, there were no significant differences in AT, maximal O₂ uptake, maximal O₂ pulse, maximal dyspnoea index, ventilatory response (ΔVE/ΔVCO₂), O₂ cost of ventilation (VO₂/W/VE), end-tidal partial pressure of carbon dioxide at maximal exercise and maximal SaO₂ among the three ACE genotype COPD patients. Maximal work load and aerobic work efficiency were higher in the COPD group with the II genotype than in those with the ID or DD genotype. There were no significant differences in resting lung function and cardiopulmonary exercise testing parameters among the three ACE genotype control groups.
Conclusions:   The ACE gene may be involved in the regulation of skeletal muscle aerobic work efficiency, but is not associated with the ventilatory responses to exercise in COPD patients.     

Efficacy and safety of entecavir in nucleoside-naive, chronic hepatitis B patients: Phase II clinical study in Japan

Background and Aim:  Entecavir has demonstrated clinical efficacy for chronic hepatitis B. This study evaluated the efficacy and safety of entecavir in nucleoside-naive Japanese chronic hepatitis B patients.
Methods:  In this multicenter, double-blind study, 66 nucleoside-naive Japanese chronic hepatitis B patients were randomized to 0.1 mg entecavir ( n  = 32) or 0.5 mg entecavir ( n  = 34) daily for 52 weeks. The primary endpoint was the proportion of patients whose serum hepatitis B virus (HBV) DNA decreased from baseline by ≥2 log₁₀ copies/mL or became undetectable (<400 copies/mL by polymerase chain reaction assay) at week 48.
Results:  One hundred percent of patients in both treatment groups achieved the primary efficacy endpoint, with 81% and 68% of patients achieving undetectable HBV DNA in the 0.1 mg and 0.5 mg treatment groups, respectively. Mean changes from baseline in HBV DNA were −4.49 log₁₀ and −4.84 log₁₀ copies/mL for the 0.1 mg and 0.5 mg groups, respectively. Significant improvements in necroinflammation were seen in both groups, as assessed by Knodell and New Inuyama classifications. Most adverse events were transient and classified as grade 1 or 2. There were no clinically significant differences in adverse events across the two treatment groups and no discontinuations due to adverse events in either group.
Conclusions:  In Japanese nucleoside-naive patients with chronic hepatitis B, 0.1 mg or 0.5 mg entecavir daily provided excellent efficacy and was well tolerated. The 0.5 mg dose was selected for the treatment of nucleoside-naive patients.