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.     

Effect of enalapril on exercise cardiopulmonary performance in chronic obstructive pulmonary disease: A pilot study

BackgroundSome studies suggest that the sympathetic nervous system and the renin–angiotensin system are activated in patients with chronic obstructive pulmonary disease (COPD), potentially resulting in negative cardiopulmonary and muscular effects. The aim of this pilot study was to evaluate the efficacy of an angiotensin converting enzyme (ACE) inhibitor on cardiopulmonary exercise performance in COPD patients. Primary outcome was the effect of treatment on the ventilatory response to exercise (VE/VCO₂ slope). Secondary outcomes were exercise variables evaluated by the cardiopulmonary exercise test, and pulmonary function according to ACE genotyping.Methods4 weeks treatment with enalapril (10 mg od) or placebo was evaluated in 21 COPD patients (FEV₁ < 60%) and without cardiovascular disease in a double-blind, cross-over study.Results18 patients completed the study. Enalapril did not exert a significant effect on exercise VE/VCO₂ slope or on peak O₂ consumption. However enalapril significantly improved peak O₂ pulse and work rate compared to placebo. A mild but significant worsening of the diffusion capacity of the lung was observed. ACE genotype did not significantly affect patients' response to treatment, except for a trend toward a more evident effect of treatment in patients with II ACE genotype in terms of O₂ pulse and gas diffusion.ConclusionsIn this pilot study, ACE inhibition did not affect the ventilatory response to exercise in COPD patients. However, treatment resulted in improvement in work rate and O₂ pulse, suggesting that ACE inhibitor therapy warrants consideration and may provide beneficial effect on the cardiovascular response to exercise in 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.     

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.     

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.     

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 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.     

Cough-reflex sensitivity to inhaled capsaicin in COPD associated with increased exacerbation frequency

Background and objective:   The causes of exacerbations in COPD patients are poorly understood. This study examined the association between cough-reflex sensitivity in patients with stable COPD and the frequency of subsequent exacerbations.
Methods:   The sampling frame for cases and controls for this study was patients attending a hospital outpatient clinic. cough-reflex sensitivity was evaluated using the log concentration of capsaicin causing five or more coughs (log C₅). Subsequent COPD exacerbations were identified prospectively via symptom-based diaries over a 12-month period.
Results:   The study group comprised 45 COPD subjects and 10 controls. Mean log C₅ was lower in the COPD group than in the control group (0.97 (95% confidence interval (CI): 0.76–1.18) versus 1.26 (95% CI: 0.81–1.71), P  = 0.095). In the COPD group, log C₅ was negatively correlated with serum CRP level ( r  = −0.36, P  = 0.02) and significantly associated with the exacerbation frequency ( r  = −0.38, P  = 0.01). Stepwise multiple regression analysis showed that cough-reflex sensitivity was significantly associated with exacerbation frequency ( r ² = 0.15, P  = 0.01).
Conclusions:   Hypersensitivity of the cough reflex to inhaled capsaicin might reflect airway inflammation in stable COPD patients, which predisposes to frequent exacerbations.     

慢性阻塞性肺疾病患者运动能力与通气效率的相关性分析

目的:通过分析二氧化碳通气当量和运动能力的关系,探讨稳定期慢性阻塞性肺疾病(COPD)患者运动中通气效率与最大运动能力的相关性。方法:选取54例稳定期COPD患者,行运动心肺功能测试,实时监测摄氧量(VO2)、分钟通气量(VE)和二氧化碳排出量(VCO2),根据公式:EqCO2=VE/VCO2计算得出静态二氧化碳通气当量(EqCO2rest)、无氧阈时二氧化碳通气当量(EqCO2at)和最大运动状态下的二氧化碳通气当量(EqCO2max)。结果:1.EqCO2rest、EqCO2at及EqCO2max呈递减趋势,差异有统计学意义(P=0.001)。2.EqCO2at与最大摄氧量(VO2max)(r=-0.294,P<0.05)、EqCO2max与VO2max(r=-0.301,P<0.05)均呈负相关;EqCO2rest与最大摄氧量占预计值的百分比(VO2max/Pred)呈负相关(r=-0.345,P<0.05)。3.肺功能GOLD 3级患者(21例)的VO2max(15.99±3.39)mL·min-1·kg-1明显低于GOLD 2级患者(25例)的VO2max[(18.88±5.36)mL·min-1·kg-1,P=0.038]。两组的EqCO2rest、EqCO2at及EqCO2max差异无统计学意义。结论:稳定期COPD患者运动中通气效率呈进行性下降趋势,这可能是导致其运动能力下降的重要因素之一。     

Melatonin protects neurons from singlet oxygen-induced apoptosis

Abstract: Singlet oxygen (O₂[¹Δg]) is a very reactive molecule that can be produced by living cells and may contribute to cytotoxicity. The pineal hormone melatonin has been reported to possess potent antioxidant activity, and to be capable of scavenging O₂(¹Δg). We investigated whether melatonin might reduce the neurotoxic action of O₂(^lΔg). The cytotoxic effect of singlet oxygen was studied in primary cultures of cerebellar granule neurons pretreated with a photosensitive dye, rose bengal, and exposed to light—a procedure that generates O₂(¹Δg). We found that this procedure triggers neuronal death, which is preceded by mitochondrial impairment (assayed by the rate of the reduction of MTT, 3-[4,5-di-methylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, into formazan), and by DNA fragmentation—a marker of apoptosis. DNA fragmentation was determined in situ by terminal deoxynucleotidyl transferase assay; cell death was assayed with 0.4% trypan blue solution—viable cells with an intact membrane are not permeable to trypan blue; dead cells are, and thus, they are stained blue. Neuroprotection was obtained with the pineal hormone melatonin. In a cell-free system, melatonin also protected the enzyme creatine kinase (EC 2.7.3.2) from the rose bengal-induced injury. The results suggest that melatonin might counteract the cytotoxic action of singlet oxygen. Further studies are needed to clarify the exact role singlet oxygen and melatonin might play in neurodegenerative diseases.     

SRD5B1 gene analysis needed for the accurate diagnosis of primary 3-oxo-Δ4-steroid 5β-reductase deficiency

Background and Aim:  We encounter hyper-3-oxo-Δ⁴ bile aciduria in patients with severe cholestatic liver disease or fulminant liver failure during the neonatal period. However, simply by bile acid analysis, it is difficult to distinguish hyper-3-oxo-Δ⁴ bile aciduria from primary 3-oxo-Δ⁴-steroid 5β-reductase deficiency.
Methods:  To determine whether 3-oxo-Δ⁴-steroid 5β-reductase ( SRD5B1 ) gene analysis is required for the accurate diagnosis of 3-oxo-Δ⁴-steroid 5β-reductase deficiency, we evaluated the laboratory data, bile acid analysis and SRD5B1 gene analysis from six patients with hyper-3-oxo-Δ⁴ bile aciduria.
Results:  Based upon the results, four patients who had developed neonatal liver failure were diagnosed as having neonatal hemochromatosis. Two patients with chronic cholestasis were diagnosed as having primary 3-oxo-Δ⁴-steroid 5β-reductase deficiency by SRD5B1 gene analysis. The SRD5B1 gene in these two patients had a heterozygous mutation, G737A (Gly 223 Glu) in one patient and C217T (Arg 50 stop) in the other.
Conclusions:  Based upon our limited data, we conclude that SDR5B1 gene analysis is required for the accurate diagnosis of 3-oxo-Δ⁴-steroid 5β-reductase deficiency. Moreover, we think that it is important to elucidate whether there is a heterozygous or a compound heterozygous mutation of the SRD5B1 gene in our two patients.     

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.     

Exercise hyperventilation chronic congestive heart failure, and its relation to functional capacity and hemodynamics.

The ventilatory response to exercise was evaluated in 26 normal sedentary men and 68 patients with chronic heart failure using the slope of the relation between minute ventilation (VE) and carbon dioxide production (VCO2). All subjects underwent maximal upright bicycle cardiopulmonary exercise testing; 33 patients also underwent right-sided cardiac catheterization. The slope of VE/VCO2 was calculated by linear regression analysis using data from all the exercise tests and the first 60% of exercise duration; a high correlation was seen between these results (r = 0.83; p less than 0.001). The slope of VE/VCO2 was significantly, though weakly, related to peak exercise work load, oxygen consumption and ventilatory threshold (r = -0.49, -0.56 and -0.49, respectively), several peak exercise hemodynamic parameters and peak exercise dead space/tidal volume ratio (r = 0.70). With use of multivariate analysis, the only independent determinants of the slope were peak exercise dead space/tidal volume ratio and cardiac index. Thus, in patients with heart failure, exercise hyperventilation can contribute to the impairment of functional capacity and can be considered a compensatory response to abnormal hemodynamics and lung blood distribution in order to keep blood gas concentrations normal.     

Impact of GH substitution on exercise capacity and muscle strength in GH-deficient adults: a meta-analysis of blinded, placebo-controlled trials

Background  Several but not all trials suggest that GH replacement in GH-deficient adults improves aerobic exercise capacity, whereas its effect on muscle strength is more dubious. However, a denominator of these studies is a low sample size.
Objective  We systematically reviewed and analysed all randomized, double-blind, placebo-controlled trials on the effects of GH administration on aerobic exercise capacity and muscle strength in GH-deficient adults.
Study selection  Fifteen trials were identified from four databases. We conducted an analysis of effects on aerobic exercise capacity, performed on either a treadmill or a bicycle ergometer, muscle strength assessed by a dynamometer, and muscle mass assessed by computerized tomography.
Results  The total number of patients included was 306 and the duration of treatment ranged from 3 to 12 months. GH replacement significantly increased aerobic exercise capacity [8·9 ± 0·8%, ( P  < 0·001)] including VO₂ max [0·17 ± 0·02 l/min ( P  < 0·001)], as well as muscle volume [7·1 ± 1·6%, ( P  < 0·001)]. In contrast, muscle strength measured in 113 patients was not significantly increased [3·2 ± 2·2% ( P  = 0·15)].
Conclusion  GH replacement in GH-deficient adults is associated with a significant positive effect on aerobic exercise capacity and muscle mass.     

Small airways obstruction syndrome in clinical practice

Background and objective:   Small airways obstruction syndrome (SAOS) is a particular pulmonary function test (PFT) pattern showing decreased VC and FEV₁ but a normal FEV₁/VC ratio and TLC. The significance of this syndrome in clinical practice has not been comprehensively investigated.
Methods:   This study retrospectively identified all patients who had performed PFT that showed a SAOS pattern at a university teaching hospital over 1 year. A simple algorithm for differential diagnosis was developed and validated.
Results:   Of the 3207 PFT performed, 153 (4.8%) showed a pattern indicating SAOS. Among these, a final diagnosis was confirmed for 85 (63.4%) of the patients. The causes of SAOS included both restrictive and obstructive lung diseases with the leading causes being early interstitial lung disease ( n  = 20; 23.3%), chest wall deformity ( n  = 12; 14.1%) and asthma ( n  = 10; 11.6%). Using a cut-off point of TLC of <95% predicted value to identify restrictive ventilatory defects ( P  = 0.002) and of ≥95% predicted combined with RV/TLC ≥55% to identify obstructive ventilatory defects ( P  < 0.001), a simplified algorithm with good accuracy (86.6%) was identified. Validation in an independent group showed accuracy of 91%.
Conclusions:   The PFT pattern called SAOS is not uncommon. The most common causes of SAOS were early interstitial lung disease, chest wall deformity and asthma. A diagnostic algorithm was proposed, which may help physicians' decision-making in their daily practice.     

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.     

Inflammatory markers in exhaled breath condensate from patients with asthma

Background and objective:   Evaluation of airway inflammation is important for the diagnosis and treatment of asthma. Exhaled breath condensate (EBC) is a minimally invasive method for assessing inflammation and may be useful for monitoring airway inflammation in asthma. The aims of this study were to establish an EBC collection method, to assess biomarkers reflecting asthmatic airway inflammation, and to determine the relationship of these biomarkers with asthma severity and lung function.
Methods:   Fifty-eight non-smoking healthy subjects, seven asymptomatic smokers, nine subjects with common cold and 55 asthmatics with disease severity ranging from mild intermittent to severe persistent were studied. The efficacy of a pipette method was compared with that of a commercial collecting device. pH, CRP, albumin, hydrogen peroxide (H₂O₂) and nitrite/nitrate levels were measured in EBC.
Results:   Except for the quantity of EBC collected and albumin levels, there were no differences between the commercial method and the pipette method in levels of biomarkers measured. Levels of CRP, H₂O₂ and nitrite/nitrate were significantly higher in the asthma group than that in the control group. In terms of asthma severity, pH and levels of CRP, H₂O₂ and nitrate were significantly higher in the mild persistent group than that in the other groups. In addition, H₂O₂ levels in EBC correlated significantly with the level of nitrite/nitrate. FEV₁ and PEF showed significant negative correlations with H₂O₂ and nitrite/nitrate levels.
Conclusion:   Measurement of EBC biomarkers is a non-invasive and useful way to evaluate airway inflammation in patients with asthma.     

Exercise responses during incremental and high intensity and low intensity steady state exercise in patients with obstructive lung disease and normal control subjects

A study was undertaken to compare the cardiac and ventilatory responses to different types of exercise between 12 patients with COPD and ten normal age-matched control subjects. Both groups attained comparable heart rates and the percentage of their maximum predicted heart rate. Patients had a higher heart rate and VE with a lower O2P at every level of work load. Patients had a mean VT which approximated their FEV1 and increased their VE predominantly by increasing their respiratory frequency. During the low intensity test, despite the differences in work load, the patients had comparable heart rates and VE. No resting spirometric value accurately predicted work load, VE, or maximal VO2. We conclude that patients have a reduced work tolerance that is not adequately explained by their reduced lung function. Thus, cardiac factors, deconditioning, and the dyspneic sensation may be determinants of exercise limitation in some patients.     

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.