OBJECTIVES--To estimate changes in the prevalence of reported symptoms of respiratory disease and reported diagnoses of asthma and bronchitis in primary school children in England between 1973 and 1986. DESIGN--Mixed longitudinal survey. SETTING--Representative sample of English primary schools in 22 areas. PARTICIPANTS--15,000 Boys and 14,156 girls each studied at least once between 1973 and 1986. DATA COLLECTED--Whether, according to the parent or guardian, the child had wheezed, wheezed on most days or nights, or had attacks of bronchitis or asthma in the past year. RESULTS--Within age groups trends in successive annual cohorts showed an increasing prevalence of asthma for each annual birth cohort (boys, 6.9%, p less than 0.001; girls, 12.8%, p less than 0.001) and of wheeze on most days or nights (boys, 4.3% per cohort, p less than 0.001; girls, 6.1% per cohort, p less than 0.001) and a falling prevalence of bronchitis (boys, -4.7% per cohort, p less than 0.001; girls, -5.8% per cohort, p less than 0.001). There was a smaller increase in the prevalence of wheeze whether or not it occurred on most days or nights, and this increase was significant only among the girls (boys, 1.0% per cohort, p greater than 0.05; girls, 1.7% per cohort, p less than 0.05). Although the rate of increase of "asthma" was greater than the rate of decrease in "bronchitis," the baseline prevalence of asthma was much lower than that of bronchitis, and the total proportion of children with either diagnosis declined slightly over the whole period. The main change was an increase in the proportion of children whose parents stated that they had persistent wheeze and yet did not have a report of either "asthma" or "bronchitis." CONCLUSIONS--These results suggest that there has been a true increase in morbidity that is not simply due to changes in diagnostic fashion. The increase is large enough to explain much if not all of the increase in admission to hospital and mortality, and it underlines the importance of an understanding of the aetiology of asthma in tackling the causes of the recent increase.

https://www.bmj.com/content/bmj/300/6735/1306.full.pdf

Has the prevalence of asthma increased in children? Evidence from the national study of health and growth 1973-86.

Mechanisms of carcinogenesis induced by alkylating agents.

Data on occurrence of nitrate, nitrite and N-nitrosocompounds in food and drinking water, and on total dietary intakes are reviewed. Metabolic, toxicological and epidemiological studies are surveyed and the implications with respect to safety evaluation are addressed. It is concluded that, on the basis of recent long-term animal studies and of clinical experience in man, the current Acceptable Daily Intake (ADI) allocated to nitrate by the Joint FAO/WHO Expert Committee on Food Additives of 0-5 mg/kg body weight/day (expressed as sodium nitrate) might be increased to 0-25 mg/kg body weight/day. Based on similar criteria, the ADI for nitrite would be 0-0.1 mg/kg body weight/day (expressed as sodium nitrite). In view of the known carcinogenicity of N-nitrosocompounds, exposure to these compounds in food should be minimized by appropriate technological means, such as lowering the nitrite concentration in preserved foods to the minimum required to ensure microbiological safety and use of inhibitors of nitrosation like alpha-tocopherol or ascorbic acid. Further work is needed to define the minimal levels of nitrite in foods needed to inhibit outgrowth of Clostridium botulinum and toxin production.

Nitrates, nitrites and N-nitrosocompounds: a review of the occurrence in food and diet and the toxicological implications.

Endogenous formation of N-nitrosoproline (NPRO) was demonstrated by monitoring its excretion in the urine of a male volunteer who had ingested vegetable juice, as a source of nitrate, and proline. The resulting NPRO was analyzed after derivatization by combined gas-liquid chromatography thermal energy analysis. The amount of total NPRO excreted in the urine was found to be proportional to the proline dose and increased exponentially with the nitrate dose ingested. Neither nitrate nor proline, when taken alone, led to a detectable increase in NPRO in urine. The amounts of NPRO formed (as estimated from the amounts excreted within 24 hr) after dosing 325 mg nitrate (NO3-) followed by 500 mg proline, ranged from 16.6 to 30.0 (mean, 23.3) micrograms per person. The simultaneous intake of ascorbic acid or alpha-tocopherol inhibited nitrosation of proline in vivo. Monitoring of NPRO or other N-nitroso compounds excreted in the urine thus appears to be a suitable procedure for estimating daily human exposure to endogenously formed N-nitroso compounds.

https://cancerres.aacrjournals.org/content/canres/41/9_Part_1/3658.full.pdf

Quantitative estimation of endogenous nitrosation in humans by monitoring N-nitrosoproline excreted in the urine.

In both health and disease, the colonic microbiota plays an important role in several areas of human physiology. This complex assemblage of microorganisms endows great metabolic potential on the large intestine, primarily through its degradative abilities. Many hundreds of different types of bacteria, varying widely in physiology and biochemistry, exist in a multitude of different microhabitats in the lumen of the large gut, the mucin layer and on mucosal surfaces. Both microbiota and host obtain clear benefits from association. For example, growth substrates from diet and body tissues, together with a relatively stable environment for bacteria to proliferate are provided by the host, which in turn has evolved to use butyrate, a bacterial fermentation product, as its principal source of energy for epithelial cells in the distal bowel. The main sources of carbon and energy for intestinal bacteria are complex carbohydrates (starches, non-starch polysaccharides). Carbohydrate metabolism is of great importance in the large intestine, since generically, and in terms of absolute numbers, the vast majority of culturable microorganisms are saccharolytic. The amounts and types of fermentation products formed by colonic bacteria depend on the relative amounts of each substrate available, their chemical structures and compositions, as well as the fermentation strategies (biochemical characteristics and catabolite regulatory mechanisms) of bacteria participating in depolymerization and fermentation of the substrates. Protein breakdown and dissimilatory amino acid metabolism result in the formation of a number of putatively toxic metabolites, including phenols, indoles and amines. Production of these substances is inhibited or repressed in many intestinal microorganisms by a fermentable source of carbohydrate. Owing to the anatomy and physiology of the colon, putrefactive processes become quantitatively more important in the distal bowel, where carbohydrate is more limiting.

Human colonic microbiota: ecology, physiology and metabolic potential of intestinal bacteria.

N-NITROSAMINES, which are thought to be causally related to human cancer1, have been found in μg kg−1 concentrations in polluted air2,3, in water4 and in tobacco products5. Foodstuffs such as cooked bacon, preserved with nitrite, have long been known to contain μg kg−1 amounts of volatile N-nitrosamines formed during cooking6. In vivo formation of N-nitrosamines, after ingestion of suitable amine precursors and nitrite, has been demonstrated in laboratory animals7. In vivo formation in human subjects with hypoacidity, gavaged with relatively massive amounts of diphenylamine plus nitrite, has been demonstrated through detection of N-nitrosodiphenylamine in the stomach contents8. In vivo nitrosation after ingestion of conventional foods has not been demonstrated so far, either in animals or man. We now report in vivo formation of volatile N-nitrosamines in man after ingestion of a midday meal consisting of a bacon, spinach and tomato sandwich and beer.

Leila Song

Papers

Formation in vivo of volatile N -nitrosamines in man after ingestion of cooked bacon and spinach

Analysis of nonionic nonvolatile N-nitroso compounds in foods