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Urinary hydroxyproline excretion in smokers, non-smokers and passive smokers
Abstract
The urinary hydroxyproline/creatinine ratio was reported to be increased after smoking, passive smoking and exposure to ambient air polluted with nitrogen dioxide. In two field studies we tried to verify the results obtained in smokers. A weak positive association was found between the hydroxyproline/creatinine ratio and cigarette consumption for male smokers. In contrast, the amount of hydroxyproline excreted in the 24-h urine was not increased in male and female smokers as compared to their non-smoking counterparts. Standardizing the data for body surface led to the same results. From the findings obtained in smokers we conclude that passive smoking does not lead to an elevation of hydroxyproline excretion either.
In addition, we measured lower amounts of creatinine excreted in the 24-h urine of male, but not female smokers and higher 24-h urine volumes in smokers of both sexes as compared with non-smokers. Whereas an inverse correlation was found between the extent of smoking and the excretion of creatinine, the association between the extent of smoking and urinary volume was positive. Both findings acting together may explain the increased hydroxyproline/creatinine ratio as seen in smokers. Therefore the hydroxyproline/creatinine ratio is not a measure of the hydroxyproline excretion in smokers, nor is its determination an appropriate method of detecting lung damaging effects due to smoking and passive smoking.
Veröffentlicht in der Reihe Biologische Arbeitsstoff‐Toleranz‐Werte (BAT‐Werte) und Expositionsäquivalente für krebserzeugende Arbeitsstoffe (EKA) , 9. Lieferung, Ausgabe 2000
Der Artikel enthält folgende Kapitel:
Einleitung
Struktur und Funktion der Niere
Filtration/Resorption
Aktive Sekretion/Resorption
Passive Diffusion
Bezugsgrößen bei der Angabe von Stoffkonzentrationen
Vor‐ und Nachteile verschiedener Bezugsgrößen
Volumen
Osmolalität
Spezifisches Gewicht
Kreatinin als Bezugsgröße
Vorteile der Bezugsgröße Kreatinin
Nachteile der Bezugsgröße Kreatinin
Schlußfolgerungen
Since the early studies of Durston and Ames in 1974, the Salmonella oxygenase test (Ames et al. 1973 b) and the bacterial fluctuation tests (Gatehouse and Delow 1979; Green et al. 1977) have been extended for the detection of mutagenic metabolites of the environmental carcinogens in urine of man and laboratory animals (Aeschbacher and Ruch 1982; Commoner et al. 1974; Durston and Ames 1974; Falck et al. 1980; Gibson et al. 1983; Kriebel et al. 1983; Legator et al. 1975; McCann and Ames 1975; Norpoth 1984). Histidine-requiring mutants of Salmonella typhimurium which revert to prototrophy by a variety of mutagens are used to detect mutagenic activity in the urine of patients receiving chemotherapeutic agents and workers exposed to various mutagens.
The indicators used to identify the effects of environmental tobacco smoke (ETS) and exposure to low level nitrogen dioxide (NO2) on the respiratory system are so weak that they can not be detected using traditional markers such as the increased prevalence of respiratory symptoms and a decrease in lung function. After studying urinary hydroxyproline (HOP) starting in 1977, we first reported the significant relationship between HOP and smoking, ETS and NO2 in the air, in 1981. Since then, the coherent association between urinary HOP and the established pathological and biological development of lung diseases has been studied. Bias problems based on confounding factors, misclassification of nonsmokers and over- or underestimation of ETS effects also have been discussed.
Among articles presented by us during the past 4 years, several papers and some arguments for and against this study on urinary HOP were introduced:
1)
The effect of cessation from smoking on the urinary excretion of hydroxyproline [19].
2)
A prospective repeated cross-sectional study on the possible health effects caused by automobile exhaust and passive smoking [20].
3)
Impact of smoking on the concentration and activity of alpha-1-antitripsin in serum, in relation to the urinary excretion of hydroxyproline. Matsuki H, Kasuga H et al., 1988.
4)
Behavior of urinary hydroxyproline and effect of cigarette smoking in silicosis. Osaka F, Kasuga H, Matsuki H et al., 1985.
5)
Opinions contrary to the relationship between urinary hydroxyproline and smoking, ETS and NO2.
We report a procedure for determining nicotine and cotinine in plasma. Nicotine is extracted from 1 ml of plasma with diethyl ether, back extracted, and analyzed by gas-liquid chromatography with a nitrogen/phosphorus detector. Nicotine and its internal standard, modaline, had retention times of 1.9 and 2.9 min, respectively. Cotinine is then extracted from the same plasma with dichloromethane and similarly analyzed. Cotinine and its internal standard, lidocaine, had retention times of 3.8 and 4.9 min. Day-to-day reproducibilities (CV) within 14% for nicotine and within 6% for cotinine are attainable for the respective concentration ranges 1-100 microgram/liter and 1-200 microgram/liter. Nornicotine and related alkaloids do not interfere. The sensitivity was such that less than 0.1 microgram (0.62 nmol) of nicotine and 0.1 microgram (0.62 nmol) of nicotine and 0.1 microgram (0.57 nmol) of cotinine could be detected per liter.
A series of epidemiologic studies on the health effects caused by smoking and air pollution with NO2 were carried out. Urinary hydroxyproline (HOP) which is excreted into the urine by catabolism of lung collagen was used as a biochemical marker. Urinary HOP of smokers increased dose-dependently with increasing numbers of cigarettes smoked and this result was accepted under blind conditions. Urinary HOP of nonsmokers also increased with increasing the amounts of involuntary smoking caused by smokers in their families although the increases in HOP by passive smoking were less than those by active smoking. Health effects caused by indoor air pollution with NO2 in winter and automobile exhaust in summer were also demonstrated using urinary HOP. The effects of cessation of smoking were followed up for 14 weeks by the decrease in urinary HOP. In practice, the HOP to creatinine ratio (HOP ratio) in random urine samples was used as representative of the 24-hour urine samples. Some confounding factors for urinary HOP were taken into consideration in these studies.
Groups of rats were exposed to four dilutions of cigarette smoke over a period of our weeks. Compared to the control (untreated) group of animals, the 24-hour hydroxyproline output (relative to creatinine) was lower for all dilutions of smoke and showed a negative dose-response relationship. In human smoking studies, in which groups of 20 male subjects and 20 female subjects were switched between various cigarettes for periods of 2 weeks, hydroxyproline output (relative to creatinine) for each sex did not change with increasing nicotine uptake although the outputs for men and women were significantly different.
Eight serum chemistry levels were studied in over 65,000 cigarette smokers and non-smokers. On the average, creatinine and albumin levels were lower in the smokers of both sexes, while the opposite was true for 1-hr post-challenge serum glucose. Globulin levels were consistently lower in the women smokers only. Uric acid concentrations were lower in the men who smoked. Cholesterol levels were higher in the white men who smoked but not in the black male smokers. Calcium and SGOT levels of smokers were quite similar to those of nonsmokers.Alcohol consumption played a role in smoker-nonsmoker differences in serum glucose concentration. However, for other chemistries no additional factors were identified that could explain the relationships to cigarette smoking. Thus they may be either directly affected by smoking or related to undefined underlying differences between smokers and nonsmokers.
Urinary hydroxyproline excretion was investigated in 125 male cigarette smokers, 194 male pipe and/or cigar smokers, and 24 male nonsmokers. Hydroxyproline excretion was calculated either as hydroxyproline/creatinine ratio or as body surface-standardized amounts of hydroxyproline excreted in urine sampled during day, during night, or over 24 hr. The association of hydroxyproline excretion with smoke uptake variables such as daily cigarette consumption, carboxyhemoglobin, serum cotinine, and nicotine in urine and with self-reported passive smoking exposure in nonsmokers was analyzed. The hydroxyproline/creatinine ratio was found to be unsuitable as a measure of hydroxyproline excretion since creatinine urine concentrations correlate inversely with smoke uptake in cigarette and pipe/cigar smokers. The amount of hydroxyproline excreted in 24-hr urine and standardized for body surface was not significantly associated with smoke uptake in pipe/cigar smokers or exposure to passive smoking in nonsmokers. In cigarette smokers the situation appeared similar, although the results were less clear-cut. The data do not favor the premise that measuring urinary hydroxyproline excretion is an accurate method of investigating a lung-damaging effect of smoking, passive smoking, or air pollution.
Biochemical determinations of plasma and salivary cotinine and thiocyanate were used to differentiate smokers from non-smokers and to follow daily smoking patterns in smokers. Results indicate that cotinine is better suited than thiocyanate to determine smoking status in large scale epidemiologic studies and to follow alterations in smoking behavior over periods of time. Salivary cotinine is a reliable alternative to plasma for validation of smoking status and for following changes in daily smoking patterns.
The relationship of weight, height, Quetelet index, hematocrit and blood levels of thyroxine, globulin, bilirubin, creatinine, aspartate aminotransferase, uric acid, alkaline phosphatase and glucose to smoking was studied in a Jerusalem population sample of youngsters aged 17 yr and their parents. Among youngsters, male smokers had a higher body mass index than did male nonsmokers. In adults, both men and women smokers were slightly leaner than ex-smokers and, in women, smokers were clearly leaner than those who had never smoked. Generally, the associations of smoking with the biochemical variables were weaker in youngsters than in adults. In men, lower mean levels of creatinine, bilirubin, aspartate aminotransferase and uric acid were observed among smokers. Hematocrit levels were somewhat higher in both young and adult smokers of both sexes, being more so in adults. Smokers showed consistently lower globulin levels than did nonsmokers. Plasma glucose levels were somewhat lower in youngsters of both sexes who smoked. Serum thyroxine levels were slightly increased in female smokers, suggesting a hormonal effect of smoking. These findings are discussed in light of the published literature.
Der klinische Nutzen der Hydroxyprolinausscheidung im Rahmen von Lungenerkrankungen
- A Romatowska-Dziub
- L Krutul
- E Kowal
Comparison of various tobacco smoke related products in nonsmokers with those in non-heavy smokers
- E Hiyashi
- S Itani
- S-I Hashimoto
- Y Shimizu
Untersuchungen zur Hydroxyprolinausscheidung im Harn bei chronischer obstruktiver Bronchitis
- M Wendel
- W Rehpenning
Urinary hydroxyproline excretion in young males exposed experimentally to nitrogen dioxide
- P Muelnaer
- H Reid
- R Morris
- L Saltzman
- D Horstman
- A Collier
- F Henderson