The dose-response association of urinary metals with altered pulmonary function and risks of restrictive and obstructive lung diseases: a population-based study in China.

OBJECTIVE: Reduced pulmonary function is an important predictor of environment-related pulmonary diseases; however, evidence of an association between exposures to various metals from all possible routes and altered pulmonary function is limited. We aimed to investigate the association of various metals in urine with pulmonary function, restrictive lung disease (RLD) and obstructive lung disease (OLD) risks in the general Chinese population. DESIGN: A cross-sectional investigation in the Wuhan cohort population. SETTING: A heavily polluted Chinese city. PARTICIPANTS: A total of 2460 community-living Chinese adults from the Wuhan cohort were included in our analysis. MAIN OUTCOME MEASURES: Spirometric parameters (FVC, forced vital capacity; FEV1, forced expiratory volumes in 1 s; FEV1/FVC ratio), RLD and OLD. RESULTS: The dose-response associations of pulmonary function, and RLD and OLD, with 23 urinary metals were assessed using regression analysis after adjusting for potential confounders. The false discovery rate (FDR) method was used to correct for multiple hypothesis tests. Our results indicated that there were positive dose-response associations of urinary iron with FEV1 and FEV1/FVC ratio, vanadium with FEV1, and copper and selenium with FEV1/FVC ratio, while a negative dose-response association was observed between urinary lead and FEV1/FVC ratio (all p<0.05). After additional adjusting for multiple comparisons, only iron was dose dependently related to FEV1/FVC ratio (FDR adjusted p<0.05). The dose-response association of iron and lead, with decreased and increased chronic obstructive pulmonary disease risk, respectively, was also observed (both p<0.05). Additionally, we found significant association of urinary zinc with RLD and interaction effects of smoking status with lead on FEV1/FVC, and with cadmium on FVC and FEV1. CONCLUSIONS: These results suggest that multiple urinary metals are associated with altered pulmonary function, and RLD and OLD prevalences.

Evaluation of blood serum, erythrocyte and urine magnesium concentrations in babies with pneumonia or bronchial obstructive bronchitis.

Physiological properties of magnesium (Mg) as a catalyst of enzymatic processes mainly are known quite well. Still unclear, however, are the changes in its concentrations in the body that occur in the course of many diseases, among others in babies with bronchial obstructive bronchitis and pneumonia. Therefore research was undertaken to determine the concentrations of magnesium in blood serum, erythrocytes and urine in babies suffering from pneumonia (54 babies) and bronchial obstructive bronchitis (46 babies). The results found that magnesium concentrations in the blood serum, erythrocytes and urine differ significantly in the groups of sick and healthy babies. Compared to the control group significantly lowest Mg concentrations in the blood serum, erythrocytes and highest in the urine were found both before and after the treatment in the babies suffering from bronchial obstructive bronchitis.

Comparison of urinary desmosine excretion in patients with chronic obstructive pulmonary disease or cystic fibrosis.

Neutrophil elastase is involved in the pathogenesis of several pulmonary diseases; a strategy for monitoring in vivo elastase activity is to measure changes in biochemical markers. The objective of this study was to determine whether differences in the urinary excretion of the elastin crosslinks, desmosine and isodesmosine (which are unique amino acid products of elastase activity), could be discerned between groups of patients with chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF), and non-diseased, age-matched controls. Twenty-four-hour urine collections were analysed to eliminate variations in excretion throughout the day, and urine was collected on four separate days in 29-31 subjects/group to investigate the variability in desmosines excretion among the groups. Both sets of patient populations had significantly more variable desmosines readings (higher standard deviations) relative to their respective age-matched control group. The means for three adult groups (COPD, controls and a COPD-smoker subset) ranged from 28.4 to 35.5 pmol desmosines/mg creatinine and there were no differences among the groups. Values in children were higher: 55 pmol desmosines/mg creatinine in the non-CF children and 77 pmol desmosines/mg creatinine for the CF group (P<0.01 vs. age-matched controls). The results of this study show that urinary desmosines, as a surrogate marker for enhanced elastase activity, are more highly variant in both patient populations relative to age-matched controls, and an overall increase in the mean value is further observed in patients with cystic fibrosis.

MEKC of desmosine and isodesmosine in urine of chronic destructive lung disease patients.

Degradation of extracellular matrix components is central to many pathological features of chronic destructive lung disorders. Desmosine and isodesmosine are elastin-derived cross-linked amino acids whose urine levels are considered representative of elastin breakdown. The aim of this study was to apply a novel methodology, based on high-performance capillary electrophoresis, to the quantification of desmosine and isodesmosine in 11 patients with stable chronic obstructive pulmonary disease (COPD), 10 with an exacerbation of COPD, nine with alpha1-antitrypsin deficiency, 13 with bronchiectasis, and 11 adults with cystic fibrosis, in comparison to 24 controls. It was found that, in patients with stable COPD, urinary desmosine levels were higher than in controls (p=0.03), but lower than in COPD subjects with an exacerbation (p< or =0.05). The highest desmosine levels were found in subjects with alpha1-antitrypsin deficiency, bronchiectasis and cystic fibrosis (p<0.001 versus stable COPD). In a short-term longitudinal study, five stable COPD patients showed a constant rate of desmosine excretion (mean coefficient of variation <8% over three consecutive days). In conclusion, the present method is simple and suitable for the determination of elastin-derived cross-linked amino acid excretion in urine, giving results similar to those obtained using other separation methods. In addition, evidence is presented that urinary desmosine excretion is increased in conditions characterized by airway inflammation, such as exacerbations of chronic obstructive pulmonary disease, bronchiectasis and cystic fibrosis. Results obtained in subjects with alphal-antitrypsin deficiency suggest that this method might be used to evaluate the putative efficacy of replacement therapy.

Chronic obstructive pulmonary disease is associated with an increase in urinary levels of isoprostane F2alpha-III, an index of oxidant stress.

Oxidative stress has been suggested as a potential mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). It has been difficult to address this hypothesis because of the limitations of conventional indices of lipid peroxidation in vivo. F2-isoprostanes (iPs) are prostaglandin isomers formed by free radical dependent peroxidation of arachidonic acid. Urinary iPF2alpha-III is a relatively abundant iPs produced in humans. In the present study, we investigated whether COPD is associated with enhanced oxidative stress by measuring urinary levels of this compound. Urinary excretion of iPF2alpha-III was determined in 38 patients with COPD and 30 sex- and age-matched healthy control subjects. Levels of iPF2alpha-III were significantly higher in patients with COPD (median, 84 pmol/ mmol creatinine; range, 38 to 321) than in healthy controls (median, 35.5 pmol/mmol creatinine; range, 15 to 65) (p < 0.0001). This elevation was independent of age, sex, smoking history, or duration of the disease. An inverse relationship was observed with the level of PaO2 (r = -0.38, p = 0. 019). Aspirin treatment failed to decrease urinary levels of iPF2alpha-III (102 +/- 8 versus 99.2 +/- 7.3 pmol/ mmol creatinine), whereas 11-dehydro TxB2 was significantly reduced (695 +/- 74 versus 95 +/- 10 pmol/mmol creatinine) (p < 0.0001). Elevated levels of iPF2alpha-III (median, 125 pmol/mmol creatinine; range, 110 to 170) in five patients with COPD declined (median, 90 pmol/mmol creatinine; range, 70 to 110) (p < 0.001) as an acute exacerbation in their clinical condition resolved. Increased urinary iPF2alpha-III is consistent with the hypothesis that oxidative stress occurs in COPD. This provides a basis for dose finding and evaluation of antioxidant therapy in the treatment of this disease.

Micellar electrokinetic chromatography for the determination of urinary desmosine and isodesmosine in patients affected by chronic obstructive pulmonary disease.

The presence in urine of desmosine (DES) and isodesmosine (IDES), two crosslinked amino acids unique to the elastic fiber network, can be used as a specific indicator of degradation of mature elastin. Compared to methodologies so far available, the capillary electrophoretic technique reported here seems to be suitable and convenient for determining desmosines in urine of patients affected by chronic obstructive pulmonary disease (COPD). By using 35 mM sodium tetraborate pH 9.3 containing 65 mM SDS as the background electrolyte, the peaks of DES and IDES could be detected in hydrolyzed urine samples from controls and patients. Owing to the simultaneous determination of endogenous urinary creatinine used as appropriate internal standard, the amount of these amino acids could be accurately quantified. The results obtained were of the same order of magnitude as the data already reported in the literature for COPD patients. Thus micellar electrokinetic chromatography (MEKC) may be considered as a reliable technique for studying the turnover of the elastic fiber in clinical conditions.

Cosinor analysis of circadian peak expiratory flow variability in normal subjects, passive smokers, heavy smokers, patients with chronic obstructive pulmonary disease and patients with interstitial lung disease.

Peak expiratory flow (PEF) presents a circadian rhythm with a maximum in the afternoon, and a significant variability in its diurnal variations has been reported in normal subjects and in chronic obstructive pulmonary disease (COPD). In order to investigate whether passive smoking, active tobacco smoking, COPD and interstitial lung disease (ILD) are associated with changes in the circadian rhythm of PEF, five groups of adult male subjects, comparable for age, weight and height, were studied: group A: 30 clinically healthy subjects who never smoked, group B: 30 subjects passively exposed to tobacco smoking, group C 30 heavy smokers (> 20 cigarettes daily for at least 5 years), group D: 30 patients with nonasthmatic COPD (emphysema and/or chronic bronchitis), and group E: 15 patients with ILD (pneumoconiosis). Active tobacco smoking and exposure to passive smoking were assessed by the determination of the urinary cotinine concentration. A portable spirometer was used to measure PEF over a whole day, at 0.00, 6.00, 8.00, 10.00, 12.00, 14.00, 16.00, 18.00, 20.00, 22.00, and 24.00 h, all subjects leading a normal life. The 'mean cosinor' method was used for statistical analyses; the PEF variability was evaluated by the amplitude percent mesor (daily mean). All groups showed diurnal fluctuations in PEF values with significant (p < 0.05) circadian rhythms. The peaks of PEF rhythms occurred in the early afternoon, without significant (p > 0.05) differences between the groups. The cosinor mean was significantly (p < 0.05) lower in heavy smokers, in passive smokers, and in COPD patients than in controls. Controls, passive smokers, heavy smokers, COPD and ILD patients presented a PEF amplitude percent mesor (95% confidence limits) of 6.26% (range 4.57-7.95), 7.79% (range 5.07-10.51), 12.60% (range 7.61-17.59), 17.19% (range 10.18-23.50), and 3.98% (range 2.09-5.87), respectively, with significant differences (p < 0.05) between all groups, except between controls and passive smokers. These data suggest that tobacco smoke, both passive and active, does not modify the circadian peak of PEF, but modifies significantly its mesor and amplitude. In this respect, heavy smokers have the same pattern of COPD: lower mesor and greater amplitude; passive smokers present an intermediate situation. An increased diurnal variability in PEF could be considered as an early index of tobacco smoke damage and of developing COPD. When studying diurnal PEF variability, active and passive smoking habits should be considered.

A comparison of nebulized budesonide with oral prednisolone in the treatment of exacerbations of obstructive pulmonary disease.

Nebulized corticosteroids in acute bronchospasm may offer topical anti-inflammatory activity while minimizing undesirable systemic effects. We compared the side-effect profile of nebulized budesonide (2 mg twice daily) with that of oral prednisolone (30 mg once daily) in a randomized parallel-group study of 19 adults with severe acute airway obstruction. Over the 5 days of the study, baseline forced expiratory volume in 1 second (FEV1) increased from 1.8 (95% confidence interval [CI], 0.7) to 2.1 (95% CI, 0.7) L in the group that received oral corticosteroids compared with 1.9 (95% CI, 0.7) to 2.0 (95% CI, 0.7) L in the group that received nebulized corticosteroid. All biochemical variables were similar at day 1. Comparison of budesonide treatment with prednisolone on day 5 showed that urinary corticosteroid metabolites were significantly higher (2012 [95% CI, 812] compared with 1079 [95% CI, 346] mg/24 hr [p < 0.05]), urinary androgen metabolites were not different, serum osteocalcin was elevated (2.3 [95% CI, 1.4] compared with 0.6 [95% CI, 0.6] ng/ml [p < 0.05]), and 24-hour urinary calcium to creatinine ratios were lower (0.28 [95% CI, 0.1] compared with 0.53 [95% CI, 0.2]), whereas urinary hydroxyproline to creatinine ratios were similar. The biochemical markers associated with corticosteroid side effects improve in patients treated with nebulized corticosteroids compared with patients who receive conventional treatment.

Altered composition of urinary heparan sulfate in patients with COPD.

In patients with emphysema the integrity of the extracellular matrix (connective tissue skeleton) is compromised. In this study we analyzed glycosaminoglycans, which are main constituents of this matrix, in urines from patients with chronic obstructive pulmonary disease (COPD)/emphysema. Glycosaminoglycans (GAGs) were purified by anion exchange chromatography and quantified using the 1,9-dimethylmethylene blue assay. Heparan sulfate (HS) was assayed using three different chemical methods: digestion with heparitinase or with nitrous acid and by use of an adapted 1,9-dimethylmethylene blue assay. A specific epitope on the HS molecule, defined by the monoclonal antibody JM403, was determined using an inhibition enzyme immunoassay. In patients with COPD total urinary glycosaminoglycan and HS content were not altered. The JM403 epitope of HS, however, was greatly decreased in patients (0.6 versus 4.1 units/mg creatinine for control subjects, p < 0.0001). A similar pattern was observed when patients with bronchial carcinoma with and without emphysema were compared (0.4 versus 2.4 units/mg creatinine respectively, p < 0.0005). Patients with sarcoidosis did not show a decreased epitope content. These results indicate a structural change or an altered processing of the HS molecule in patients with emphysema. Taking into consideration the importance of HS for the stability of the alveolar extracellular matrix, this change may be associated with the pathogenesis of emphysema.

Relación entre microalbuminuria y función pulmonar en enfermedad pulmonar obstructiva crónica (EPOC)

Introducción: Se sospecha que la alteración de órganos y sistemas diferentes del respiratorio, entre ellos el riñon y el endotelio, es frecuente en pacientes con EPOC. Los estudios de evaluación funcional glomerular en EPOC son escasos y han sido objeto de serias críticas. La excreción urinaria de albúmina es una medida muy sensible de alteración glomerular y endotelial. Objetivo: Evaluar la prevalencia de microalbuminuria en sujetos con EPOC sin otras causas de lesión glomerular y relacionarla con las pruebas funcionales respiratorias estándar. Pacientes y Métodos: Treinta y dos pacientes con edad promedio de 60 años, con EPOC moderado a severo (promedio del VEF1/CVF 49 por ciento del predicho) e hipoxemia leve (PaO2 promedio 52 mmHg) para la altura de Santafé de Bogotá (2640 m). Se realizaron exámenes de curva flujo-volumen, espirometría y gases arteriales, recolección de una muestra de orina durante seis horas para determinación de excreción de albúmina y uroanálisis y determinación de creatinina sérica en sangre venosa. Se buscaron relaciones entre la excreción de albúmina y los demás valores de función respiratoria, oxigenación y equilibrio ácido-básico (coeficiente de correlacción de Pearson) y diferencias entre grupos (ANOVA, Kruskal Wallis H). Resultados: La prevalencia de microalbuminuria patológica (30 microgramos/minuto) fue de 3,12 por ciento (1/32 pacientes). No hubo asociación significativa entre ninguna variable descriptiva, del estado funcional, la severidad de la obstrucción, la oxigenación y excreción urinaria de albúmina. Tampoco se demostró diferencia en la excreción de albúmina entre grupos al separarlos de acuerdo con el grado de obstrucción. Conclusión: La prevalencia de microalbuminuria en estos sujetos con EPOC, sin otros factores de riesgo para la lesión endotelial, es baja (31,12 por ciento) y la magnitud de la excreción urinaria de albúmina no esta determinada por la obstrucción espiratoria ni por la hipoxemia arterial. Aunque es necesario realizar otras pruebas de función endotelial, parece que este órgano no es afectado de manera directa por la EPOC

Clinical pharmacokinetics of meropenem after the first and tenth intramuscular administration.

We investigated the pharmacokinetics of meropenem after the first and tenth i.m. administration in patients with respiratory tract infections. Ten patients (mean age 63.8 +/- 5.2 years) received meropenem 500 mg tds for at least ten doses, and plasma and urine antibiotic concentrations were determined by microbiological assay. After the first injection a mean peak plasma concentration of 7.93 +/- 1.29 mg/L was observed at 1 h. Trough levels at 8 h (0.29 +/- 0.16 mg/L) were detectable in five of ten treated patients. The mean terminal half-life was 1.08 +/- 0.2 h with an area under the curve (AUC) value of 23.8 +/- 4.59 mg/L.h, and a cumulative urinary recovery at 8 h of 48.43 +/- 3.12%. There was no evidence of change in the pharmacokinetics of meropenem after repeated i.m. administration, though the mean peak plasma concentration and AUC value were slightly increased. The accumulation ratio (assessed using AUC values) was 1.18 +/- 0.19 after multiple doses and was considered to be of little kinetic and clinical importance. Moreover, many of the trough concentrations of meropenem were below the limit of detection of the assay. After i.m. administration meropenem concentrations exceeded 0.5 mg/L for longer than previously described following i.v. infusion. No adverse events were reported.

Elastin and collagen degradation products in urine of smokers with and without chronic obstructive pulmonary disease.

It has been hypothesized that emphysema results from damage to the elastic fiber network of the lungs as a result of elastase-antielastase imbalance. We used a new assay for urinary desmosine (DES) and isodesmosine (IDES), specific markers for the degradation of mature crosslinked elastin, and hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), specific markers for the degradation of mature crosslinked collagen, in order to examine elastin and collagen degradation in relation to current cigarette smoking and the presence of chronic obstructive pulmonary disease (COPD). The study sample consisted of 22 never-smokers (NSM group), 13 current smokers without airflow obstruction (SM group), and 21 patients with COPD (COPD group), including both current and former smokers. The relation between the creatinine-height index and FEV1 was used to correct for possible loss of muscle mass and decreased excretion of creatinine in the COPD group. Mean urinary excretion of elastin-derived crosslinks in the COPD group (DES, 11.8 +/- 5.1 [mean +/- SD]; IDES, 11.3 +/- 5.0 micrograms/g creatinine) and in the SM group (DES, 11.0 +/- 4.2; IDES, 10.2 +/- 2.5 micrograms/g creatinine) was significantly higher than in the NSM group (DES, 7.5 +/- 1.4; IDES, 6.9 +/- 1.3 micrograms/g creatinine). In multivariate analysis, current smoking and the presence of COPD were significantly and independently associated with higher urinary excretion of elastin degradation products, and there was no significant interaction between current smoking and the presence of COPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of angiotensin converting enzyme inhibition on sodium excretion in patients with hypoxaemic chronic obstructive pulmonary disease.

BACKGROUND: Some patients with hypoxaemic chronic obstructive pulmonary disease (COPD) develop cor pulmonale with sodium and water retention. The sodium retention has been explained as a result of increased plasma levels of aldosterone. If this was true angiotensin converting enzyme (ACE) inhibition would be expected to lower plasma levels of aldosterone and improve the renal excretion of sodium. METHODS: Six patients with stable hypoxaemic COPD (PaO2 < 8.0 kPa) and a history of an oedematous exacerbation received an intravenous hypertonic saline load (6 ml/kg body weight of 2.7% saline over one hour) before and while taking 4 mg/day perindopril, an ACE inhibitor, for one month. Aldosterone, antidiuretic hormone (ADH), plasma and urine electrolyte levels, osmolality, and volume were measured over four hours. The repeatability of the saline load test was assessed in six patients with a similar severity of hypoxaemic COPD. For comparison the saline load test was also performed in six patients with mild COPD. RESULTS: The hypertonic saline load test results were repeatable. Perindopril reduced the mean (SD) plasma level of aldosterone from 142 (88) pg/ml to 54 (24) pg/ml at 0 minutes before the saline infusion, and from 64 (35) pg/ml to 30 (17) pg/ml after the infusion without improving the urinary volume or sodium excretion. Before starting treatment with perindopril 43.7 (6.9) mmol (20%) of the sodium load was excreted compared with 49.6 (7.9) mmol (22% of load) when taking perindopril. Patients with mild COPD excreted more sodium (77.6 (21.4) mmol (38.7% of load)) despite having similar plasma aldosterone levels to those in the patients receiving perindopril. CONCLUSIONS: Patients with stable hypoxaemic COPD have an impaired ability to excrete sodium which is not improved by the administration of an ACE inhibitor. ACE inhibition lowered the plasma level of aldosterone without improving sodium excretion. This suggests that the inability of patients with hypoxaemic COPD to excrete sodium is not caused by their increased plasma levels of aldosterone.

Increased 24-hour endothelin-1 urinary excretion in patients with chronic obstructive pulmonary disease.

Abnormalities in endothelin-1 (ET-1) pulmonary metabolism have been reported in patients with pulmonary hypertension, asthma and chronic obstructive pulmonary disease (COPD). In this study we have evaluated the 24-hour urinary excretion of ET-1 in COPD patients both during acute exacerbation and stable phase of the disease. ET-1 plasma and urinary levels were measured in 13 COPD patients on admission to the hospital for an acute exacerbation and at the recovery period. Ten healthy volunteers were also studied. Determination of plasma and 24-Hour urinary ET-1 levels were carried out with a radioimmunoassay test. Plasma ET-1 levels in COPD patients were similar during exacerbation and recovery and were not significantly different from those in the healthy subjects. 24-hour urinary excretion of ET-1 was increased in COPD patients during acute exacerbation; it decreased during recovery, but remained elevated when compared to normal subjects. A negative correlation was found between arterial oxygen pressure and ET-1 excretion; no correlation was found between plasma and urinary ET-1 values. In conclusion, COPD patients excrete higher amounts of ET-1 compared to healthy subjects. Urinary ET-1 values are further increased during acute exacerbation of the disease.

[Enteral nutrition in patients with chronic obstructive bronchopathy treated by artificial ventilation. Effect of conventional feeding on anthropometric and biochemical parameters]. / Nutrition entérale chez le bronchopathe chronique obstructif soumis à une ventilation artificielle. Influence d'une alimentation conventionnelle sur les paramètres anthropométriques et biochimiques.

The influence of conventional gastric tube feeding on anthropometric and biochemical parameters was studied prospectively during 12 months in 14 patients with chronic obstructive lung disease put on mechanical ventilation for respiratory failure. The anthropometric parameters were: body weight, tricipital skin fold, brachial and brachial muscle circumferences. The biochemical parameters included albumin, transferrin, retinol binding protein, transthyretin, acid alpha-1-glycoprotein, C-reactive protein, fibronectin and amino acids in blood, and 3-methylhistidine in urine. Measurements were performed on inclusion, then every 3 days until D15. After 15 days of a nutrition bringing 28.8 +/- 8.9 calories/kg/day and 13.9 +/- 2.2 grams of nitrogen per day, no improvement in anthropometric parameters was observed. On D0, comparisons with healthy controls showed that visceral serum proteins levels were significantly lower and inflammatory proteins levels significantly higher (P < 0.05); the levels of protein metabolism markers were higher, but not significantly, and those of the principal glucose-forming amino acids were significantly lower (P < 0.01). On D15, comparisons with the initial values showed that the values of retinol binding protein and transthyretin were increased (P < 0.05 and 0.01 respectively), whereas the values of the other visceral proteins were little modified; yet their concentrations remained significantly lower than those found in controls, except for the retinol binding protein. Inflammatory proteins levels were high, with a significant (P = 0.05) difference for the acid alpha-1-glycoprotein, and the patients remained in slight catabolism while their nitrogen balance was positive. These results should encourage to carry out studies on the qualitative composition of artificial nutrition in order to optimize its effectiveness in the treatment of these patients.

Overnight urinary uric acid: creatinine ratio for detection of sleep hypoxemia. Validation study in chronic obstructive pulmonary disease and obstructive sleep apnea before and after treatment with nasal continuous positive airway pressure.

During hypoxia ATP degradation to uric acid is increased in animal models and humans. To assess the reliability of an overnight increase in uric acid excretion as a marker of nocturnal hypoxemia, we selected 10 normal volunteers (7 males and 3 females), 29 COPD patients (26 males and 3 females), and 49 subjects with obstructive sleep apnea (OSA) (43 males and 6 females). The patients underwent standard polysomnography, which was repeated in 14 subjects with nasal continuous positive airway pressure (CPAP), and were subdivided into two groups: Group D included desaturating subjects who spent at least 1 h at SaO2 < 90% and 15 min below 85%, and Group ND were nondesaturating subjects. The overnight change in the uric acid:creatinine ratio (delta UA:Cr) was negative in normal subjects (-27.5 +/- 9.1 [mean +/- SD]) and ND groups: -19.7 +/- 14.3 in COPD, -16.1 +/- 13.0 in OSA. In both COPD and OSA Group D, the ratio was usually positive: delta UA:Cr was 17.9 +/- 31.4 in Group D COPD (p < 0.001 versus ND) and 10.1 +/- 30.7 in Group D OSA (p < 0.001 versus ND and versus normal subjects) despite 4 of 15 false negative results in COPD and 8 of 20 in OSA. CPAP effective treatment induced a marked reduction ((p = 0.0024) in delta UA:Cr, leading to a negative value. We conclude that delta UA:Cr seems to be a promising index of significant nocturnal tissue hypoxia, with good specificity but poor sensitivity (about 30% false negative), which might be useful for the long-term follow-up of outpatients on nasal CPAP with a positive ratio at baseline.