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ORIGINAL ARTICLE
Year : 2014  |  Volume : 27  |  Issue : 2  |  Page : 310-315

Passive smoking as a stress factor in diabetic children


1 Department of Pediatric, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department ofClinical Pathology, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission06-May-2013
Date of Acceptance25-Sep-2013
Date of Web Publication26-Sep-2014

Correspondence Address:
Rabab A Elsabagh
MBBCh, El Roda, Berkett-Elsaba, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.141685

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  Abstract 

Objective
This study aimed to measure urinary cotinine level and urinary cotinine/creatinine ratio as a biomarker of passive smoking in diabetic children.
DNA damage was estimated in peripheral leukocytes by a DNA fragmentation assay in diabetic children.
Background
Exposure to passive smoking is associated with a number of health hazards such as prenatal damage to the fetus, poor growth, respiratory illness, atopy and asthma, coronary heart disease, and sudden infant death syndrome.
Patients and methods
This study was carried out on 54 diabetic children attending the Genetic and Endocrine Unit of the Pediatric Department, Faculty of Medicine, Menoufia University.
The children were divided into two groups: group I (34 children exposed to passive smoking) and group II (20 children not exposed to passive smoking).
The studied groups were subjected to a detailed assessment of history, thorough clinical examination, investigations, and family counseling.
Results
Significantly higher urinary cotinine levels and urinary cotinine/creatinine ratios were found in children with a history of exposure to passive tobacco smoke (120.4 ± 86.2 and 173.7 ± 130.1, respectively) in comparison with children with no history of exposure (2901.5 ± 1423.2 and 3284.7 ± 2322.8, respectively, P ≤ 0.000), and the urinary cotinine levels were found to be dependent on the daily exposure to tobacco smoke as indicated by the number of cigarettes consumed by the smoker in the presence of the child. Also, significantly higher positive gel electrophoresis results (DNA damage) were found in children with a history of exposure to passive tobacco smoke (29.4%) in comparison with children with no history of exposure (0%).
Conclusion
Passive smoking is a risk factor for many health hazards and cotinine is a valuable biomarker for assessment of exposure to second-hand smoking, especially among children. Also, passive smoking is a cause of enhanced apoptotic changes in diabetic children.

Keywords: Biomarker, cotinine, diabetic, DNA damage, passive smoking


How to cite this article:
El-Ella SS, Tawfik MA, El Bassuoni MA, Elsabagh RA. Passive smoking as a stress factor in diabetic children. Menoufia Med J 2014;27:310-5

How to cite this URL:
El-Ella SS, Tawfik MA, El Bassuoni MA, Elsabagh RA. Passive smoking as a stress factor in diabetic children. Menoufia Med J [serial online] 2014 [cited 2020 Feb 16];27:310-5. Available from: http://www.mmj.eg.net/text.asp?2014/27/2/310/141685


  Introduction Top


Diabetes mellitus (DM) is a common, chronic, metabolic syndrome characterized by hyperglycemia as a cardinal biochemical feature. Type 1 DM is the most common endocrine metabolic disorder of childhood and adolescence, with important consequences for physical and emotional development. Individuals with type 1 DM require major lifestyle modifications that include an absolute daily requirement of exogenous insulin, the need to monitor their own glucose level, and the need to pay attention to dietary intake [1].

Passive smoking is the involuntary inhalation of tobacco smoke by individuals other than the intended 'active' smoker. It occurs when tobacco smoke permeates any environment, causing its inhalation by individuals within that environment. Exposure to second-hand tobacco smoke causes disease, disability, and death. Passive smoking is also known as second-hand smoke (SHS) or environmental tobacco smoke (ETS) [2].

There is a growing evidence to suggest that smoking is an independent risk factor for DM. Several hypotheses have been proposed to explain this link. Smoking has been identified as a risk factor for insulin resistance, a precursor for DM. Smoking has also been associated with a risk of chronic pancreatitis and pancreatic cancer, suggesting that tobacco smoke may be toxic to the pancreas [3],[4]. There is evidence that smoking cessation improves insulin sensitivity, whereas passive smoking reduces insulin sensitivity and increases the risk of metabolic syndrome [5].

Apoptosis is a highly regulated form of cell death defined by distinct morphological and biochemical features [6].

The molecular mechanism by which tobacco smoke triggers apoptosis remains unclear. However, it has been proven to be through the nuclear factor-kB (NF-kB) pathway. Tobacco smoke resulted in inhibition of NF-kB activity and downregulation of NF-kB-dependent antiapoptotic protein, including Bcl-2 and Bcl-x1. However, tobacco smoke enhanced the apoptotic pathways including caspase 8 and caspase 9. Mitochondrial pathway and effectors caspase 3 were activated following tobacco smoke exposure. Tobacco smoke exposure did not alter the levels of p53 and Bax proteins [7]. Cotinine, a nicotine metabolite detected in urine, has been recommended as a quantitative measure of nicotine intake and thus as a marker for ETS exposure in humans. A significant correlation was found between the nicotine levels in indoor air and the urinary cotinine to creatinine ratio of passive smokers [8].

The aim of this work was to study the effect of passive smoking measured by the urinary cotinine/creatinine ratio on apoptosis of peripheral blood lymphocytes in diabetic children.


  Patients and methods Top


This study was carried out on 54 diabetic children (only 54 children were available); they were recruited from Genetic and Endocrine Unit, Pediatric Department, Menoufia University Hospital, Egypt, during the period from December 2011 to March 2012.

They were divided into two groups. Group I included 34 diabetic children exposed to passive smoking, 18 (53%) girls and 16 (47%) boys.

Group I was further classified into two subgroups according to the smoking index (SI) (mild, SI < 200; moderate, SI between 200 and 400; and heavy, SI > 400) [9].

Group IA: these children were moderately exposed to passive smoking (SI = 200-400).

Group IB: these children were heavily exposed to passive smoking (SI > 400).

Group II included 20 diabetic children not exposed to passive smoking, seven (35%) girls and 13 (65%) boys.

Exclusion criteria

Newly diagnosed patients of less than 3 years' duration, patients with acute complications such as ketoacidosis or hypoglycemia, and patients with no history of passive smoking were excluded from the study.

All the children studied were subjected to detailed assessment of history with a focus on history of exposure to passive smoking, thorough clinical examination, investigations including estimation of DNA damage in peripheral leukocytes and measurement of cotinine level by a competitive enzyme immunoassay for the specific detection of cotinine in urine samples), and family counseling.


  Results Top


The results of this study are presented in [Table 1],[Table 2],[Table 3],[Table 4] and [Table 5] and [Figure 1],[Figure 2] and [Figure 3].
Figure 1:

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Figure 2:

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Figure 3:

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Table 1:Comparison of laboratory investigations among the groups studied

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Table 2: Comparison of gel electrophoresis results between the groups studied

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Table 3: Comparison of gel electrophoresis results, urinary cotinine level, and urinary cotinine/creatinine ratio between the groups studied

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Table 4: Relation of smoking index and laboratory investigations between group IA and group IB

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Table 5: Comparison between urinary cotinine level and urinary cotinine/creatinine ratio in terms of the smoking index

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There was no statistically significant difference between the studied groups in Hba1C and urinary creatinine (P > 0.05), whereas the mean values of urinary cotinine level and urinary cotinine/creatinine ratio were significantly higher in group I (P = 0.000)

The results of gel electrophoresis were significantly different between the groups studied as follows: DNA damage was found to be higher in samples of group I (29.4%) when compared with those of group II (0%).

Urinary cotinine level and urinary cotinine/creatinine ratio were significantly higher in group I than in group II in terms of gel electrophoresis results.

Urinary cotinine level was highly significant in terms of the SI level. Urinary cotinine/creatinine ratio, Hba1C, and gel electrophoresis results were significant in terms of the SI level. Urinary creatinine level was not significant in terms of the SI level.

A significantly higher urinary cotinine concentration was found among those with a moderate SI compared with those with a heavy SI.

Results of family counseling

All families understood the hazards of smoking on the smokers and nonsmokers, especially children, as they breathe faster than adults, stay at home for long periods, and are exposed to both SHS and third-hand smoking. Some families agreed to quit smoking. Other families agreed to quit smoking at home only. Some families could not be convinced to quit smoking.


  Discussion Top


This study investigated the relationship between passive smoking and apoptosis of peripheral blood lymphocytes in diabetic children.

In total, 54 diabetic children at the Genetic and Endocrine Unit, Pediatric Department, Menoufia University, Egypt, were studied.

The demographic data of the studied groups (group I exposed to passive smoking) and (group II, control) shows that the children were between 4 and 16 years of age, mean age 11.5 ± 3.88 years. There were 25 (46.3%) girls and 29 (53.7%) boys; 26 (48.1%) of these children were from rural areas and 28 (51.9%) were from urban areas.

In this study, the mean age of the children in group I (exposed to SHS) was 12.9 ± 2.78 years, whereas that of children in group II (not exposed to SHS) was 9.07 ± 4.3.

In our study, the only current smoker in the exposed group was the father (70.6%), father and relatives (14.6%), father and professor (5.9%), father and peers (2.9%), and father and others (5.8%). All mothers reported a negative history of smoking. This would mean that the mother is not an active smoking member in the Egyptian family or there is a possibility that they denied that they smoked. These data are not consistent with a cross-sectional study carried out on children in Turkey, in which among the groups studied, the father was a smoker in 50.7%, the mother was a smoker in 13.2%, and both parents were smokers in 33.1% [10].

In contrast, in another a cross-sectional survey on tobacco use in the city of Alexandria, Egypt, the prevalence of current smoking was significantly higher among men (48.5%) than women (1.5%) [11].

The results of this study showed that there was a significant higher mean urinary cotinine excretion and urinary cotinine/creatinine ratio among children with a history of indoor exposure to tobacco smoke (120.4 ± 86.2 and 173.7 ± 130.1 ng/mg, respectively) in comparison with children with no history of indoor exposure (2901.5 ± 1423.2 and 3284.7 ± 2322.8 ng/mg) (P≤ 0.000 and P ≤ 0.000, respectively).

These results are in agreement with those of Seifert et al. [12], who found that children with some form of reported ETS exposure had urinary cotinine levels that were 7.5 times higher than those who were not exposed.

These results are markedly higher than those of Scherer et al. [13], who found that urinary cotinine/creatinine ratios were 29.4 and 4.5 ng/mg in the exposed and the nonexposed group, respectively (P < 0.001).

Urinary cotinine excretion and the urinary cotinine/creatinine ratio in the present work were found to be dependent on daily exposure to tobacco smoke as indicated by the number of cigarettes consumed by the smoker in the presence of the child. We found significantly higher mean urinary cotinine excretion and urinary cotinine/creatinine ratios among children with a history of heavy indoor exposure (88.4 ± 69.0 and 140.0 ± 127.4, respectively) in comparison with children with a history of moderate indoor exposure to tobacco smoke (197.0 ± 76.5 and 254.7 ± 101.1, respectively) (P ≤ 0.000 and P ≤ 0.017, respectively).

These results are in agreement with those of Olivieri et al. [14], who found that the number of cigarettes smoked by parents correlates with the urinary cotinine levels.

These results are in agreement with those of Seifert et al. [12], who found decreasing levels of cotinine as reported exposure decreased.

Similarly, Reevs and Bernstein [15] found a positive correlation between reported amount of smoking and measurable levels of cotinine.

Our results indicate that urinary cotinine is a sensitive marker for the assessment of exposure to tobacco smoke. These results are in agreement with those reported by Blackburn et al. [16] in a cross-sectional survey of infants in England.

In our study, we found a significantly higher mean Hba1C and DNA damage among children with a history of heavy indoor exposure (7.3 ± 2.3 and 1.0 ± 0.0, respectively) in comparison with children with a history of moderate indoor exposure to tobacco smoke (8.9 ± 1.8 and1.4 ± 0.5, respectively) (P 0≤ 0.037 and P ≤ 0.014, respectively).

In our study, group I, with a history of indoor exposure to tobacco smoke, showed highly significant positive gel electrophoresis results (DNA damage) in comparison with group II, with no history of indoor exposure to tobacco smoke (P < 0.007). The results of the present study indicated significant positive gel electrophoresis results (DNA damage) among group I children with higher mean urinary cotinine levels and urinary cotinine/creatinine ratios (64.0 ± 52.1 and 79.51 ± 59.52, respectively) in comparison with the children in group II, with lower mean urinary cotinine levels and urinary cotinine/creatinine ratios (143.83 ± 87.5 and 212.97 ± 131.98, respectively) (P 0≤ 0.00 and P ≤ 0.005, respectively).

The effect of active smoking (in patient with COPD) on peripheral blood lymphocytes was studied by Hodge et al. [17], who found that peripheral blood T-lymphocyte apoptosis was enhanced in the patient group (70.0 ± 23.1%) compared with the control group (58.2 ± 15.9%) (P = 0.043). The enhanced apoptotic pathway caused by passive smoking was explained by Zhong et al. [7], who reported that tobacco smoke enhanced the apoptotic pathways including caspase 8 and caspase 9 (mitochondrial pathway) as well as effector caspase 3. Exposure of rats to 80 mg/m 3 tobacco smoke significantly induced apoptosis in the lungs [7].

These findings are in agreement with those of Sdralia et al. [18], who found that low doses of gas-phase cigarette smoke induce apoptosis in cultured T lymphocytes, whereas at high doses, gas-phase cigarette smoke leads to necrotic death, bypassing the characteristic stage of caspase 3 activation and, thus, the apoptotic route.

These findings are in agreement with those of Wu et al. [17], who found that cigarette smoking induces lung injury including apoptosis by two mechanisms:

  1. Phosphorylation of the JNK MAPK pathway, followed by either activation of FasL or Bcl-2, and
  2. An increase in Bax, with stimulation of the expression of phosphor-p53, thus leading to the activation of cleaved caspase 3.


This effect may induce apoptosis and may be an important pathway in the lung pathogenesis of cigarette smoking [17].

The findings are in good agreement with those of Bijl et al. [19], who found that smoking was associated with an increase in the percentage of Fas-expressing lymphocytes. This might render these cells more susceptible to apoptosis. No differences in the percentages of circulating apoptotic lymphocytes could be found between smoking and nonsmoking individuals [%lymphocytes annexin V in nonsmoker (4.0 ± 3.4)/smokers (5.6 ± 8.9), P = 0.82] [19].

This study found a significant correlation between urinary cotinine, urinary cotinine/creatinine ratio, and peripheral blood lymphocyte apoptotic parameters. These findings are consistent with those of Hakki et al. [20], who investigated the effect of nicotine on DEX-induced expression of active caspase 3, a marker for apoptosis, in murine thymus and spleen cells. Nicotine significantly decreased the DEX-induced active caspase 3 immunoactivity of both thymocytes and splenocytes [20].

Family counseling of smokers' families was performed on two visits:

During the first visit, we provided information on the hazards of both active and passive smoking, and discussed the types of passive smoking (SHS and third-hand smoking).

During the second visit, we discussed the results of urinary cotinine levels and their correlation with the frequency of infections (RTIs, otitis media), and the relation between urinary cotinine level and number of packs consumed by the smoker or the place of exposure.

Advice on how to quit smoking was provided by explaining the health hazards of smoking for both active and passive smokers, the benefits of stopping smoking for the smoker, the smoker's family, and community, and simple ways to stop smoking including reduction of nicotine absorption (e.g. not hold smoke deeply).

As a result of family counseling, some families agreed to quit smoking, other families agreed to quit smoking at home only, and some families could not be convinced to quit smoking.

We can conclude that passive smoking is one of the most common preventable health hazards in our community and it is considered a risk factor for many diseases such as DM, and is also considered as a cause of enhanced apoptotic changes in diabetic children.

Cotinine, a nicotine metabolite detected in urine, has been recommended as a quantitative measure of nicotine intake and thus as a marker for ETS exposure in humans. Therefore, we recommend the use of cotinine as a biomarker of ETS exposure, especially in children.

A smoke-free policy, in which no one is allowed to smoke inside the house at any time under any circumstances, is more effective in reducing smoking than partial restrictions, and also family counseling programs targeted at parents to help them quit smoking by explaining health hazards of smoking on both active and passive smokers, especially children, the benefits of quitting smoking, and ways to quit smoking.


  Conclusion Top


Passive smoking is a risk factor for many health hazards and cotinine is a valuable biomarker for the assessment of exposure to SHS, especially for children. Also, passive smoking is a cause of enhanced apoptotic changes in diabetic children.

Recommendations

  1. A national strategy should be implemented to combat indoor passive smoking.
  2. Revise the Egyptian housing features and cigarettes composition to explain why passive smoking effects are as high as that of active smoking abroad.
  3. Public education campaigns should be conducted to encourage smokers to adopt smoke-free homes.



  Acknowledgements Top


Conflicts of interest

There are no conflicts of interests.[21]

 
  References Top

1.Alemzadeh R, Wyatt DT. Diabetes mellitus in children. In: Bebrman RE, Vanghan V, Melson, editors. Nelson textbook of pediatrics. 17th ed. Philadelphia, London: WB Saunders Company; 2004. 1947-1971.  Back to cited text no. 1
    
2. Moritsugu KP. The 2006 Report of the Surgeon General: the health consequences of involuntary exposure to tobacco smoke. Am J Prev Med 2007; 32 :542-543.  Back to cited text no. 2
    
3. Yolton K, Khoury J, Hornung R, Dietrich K, Succop P, et al. Environmental tobacco smoke exposure and child behaviors. J Dev Behav Pediatr 2008; 29 :450-457.  Back to cited text no. 3
    
4. Houston TK, Person SD, Pletcher MJ, Iribarren C, Kiefe CI, et al. Active and passive smoking and development of glucose intolerance among young adults in a prospective cohort: CARDIA study. BMJ 2006; 332 :1064-1069.  Back to cited text no. 4
    
5. He Y, Lam TH, Jiang B, Wang J, Feng K. Prevalence of the metabolic syndrome and its relation to cardiovascular disease in an elderly Chinese population. J Am Coll Cardiol 2006; 47 :1588-1594.  Back to cited text no. 5
    
6. Thiede B, Treumann A, Kretschmer A, Söhlke J, Rudel T. Shotgun proteome analysis of protein cleavage in apoptotic cells. Proteomics 2005; 5 :2123-2130.  Back to cited text no. 6
    
7. Zhong CY, Zhou YM, Pinkerton KE. NF-kappa B inhibition is involved in tobacco smoke-induced apoptosis in the lungs of rats. Toxicol Appl Pharmacol 2008; 230 :150-158.  Back to cited text no. 7
    
8. Kim H, Lim Y, Lee S, Park S, et al. Relationship between environmental tobacco smoke and urinary cotinine levels in passive smokers at their residence. J Expo Anal Environ Epidemiol 14 :2004; S65-S70.  Back to cited text no. 8
    
9. Nitti V, de Michele G, Famiglietti B, Miniccuci E, Ortolani G, Sessa T, Lauro N. Epidemiology survey of chronic bronchitis in the city of Napels with special reference to the role and possible interaction of various exogenous factors. Bull Int Union Tuberc 1976; 51 :685-699.  Back to cited text no. 9
    
10.Boyaci H, Etiler N, Duman C, et al. Environmental tobacco smoke exposure in school children: parent report and urine cotinine measures. Pediatr Int 2004; 48 :382-389.  Back to cited text no. 10
    
11.Youssef RM, Abou-Khatwa SA, Fouad HM. Prevalence of smoking and age of initiation in Alexandria, Egypt. East Mediterr Health J 2002; 8 :626-637.  Back to cited text no. 11
    
12.Seifert JA, Ross CA, Norris JM. Validation of a five-question survey to assess a child′s exposure to environmental tobacco smoke. Ann Epidemiol 2002; 12 :273-277.  Back to cited text no. 12
    
13.Scherer G, Meger-Kossien I, Riedel K, Renner T, Meger M. Assessment of the exposure of children to environmental tobacco smoke (ETS) by different methods. Hum Exp Toxicol 1999; 18 :297-301.  Back to cited text no. 13
    
14.Olivieri M, Bodini A, Peroni DG, Costella S, Pacifici R, et al. Passive smoking in asthmatic children: effect of a ′smoke-free house′ measured by urinary cotinine levels. Allergy Asthma Proc 2006; 27 :350-353.  Back to cited text no. 14
    
15.Reeves S, Bernstein I. Effects of maternal tobacco-smoke exposure on fetal growth and neonatal size. Expert Rev Obstet Gynecol 2008; 3 :719-730.  Back to cited text no. 15
    
16.Blackburn CM, Bonas S, Spencer NJ, Coe CJ, Dolan A, et al. Parental smoking and passive smoking in infants: fathers matter too. Health Educ Res 2005; 20 :185-194.  Back to cited text no. 16
    
17.Wu CH, Lin HH, Yan FP, Wu CH, Wang CJ. Immunohistochemical detection of apoptotic proteins, p53/Bax and JNK/FasL cascade, in the lung of rats exposed to cigarette smoke. Arch Toxicol 2006; 80 :328-336.  Back to cited text no. 17
    
18.Sdralia ND, Patmanidi AL, Velentzas AD, Margaritis LH, Baltatzis GE, et al. The mode of lymphoblastoid cell death in response to gas phase cigarette smoke is dose-dependent. Respir Res 2009; 10 :82.  Back to cited text no. 18
    
19.Bijl M, Horst G, Limburg PC, Kallenberg CG. Effects of smoking on activation markers, Fas expression and apoptosis of peripheral blood lymphocytes. Eur J Clin Invest 2001; 31 :550-553.  Back to cited text no. 19
    
20.Hakki A, Pennypacker K, Eidizadeh S, Friedman H,Pross S. Nicotine inhibition of apoptosis in murine immune cells. Exp Biol Med 2001; 226 :947-953.  Back to cited text no. 20
    
21.Hodge SJ, Hodge GL, Reynolds PN, Scicchitano R, Holmes M. Increased production of TGF-beta and apoptosis of T lymphocytes isolated from peripheral blood in COPD. Am J Physiol Lung Cell Mol Physiol 2003; 285 :492-499.  Back to cited text no. 21
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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