Clinical trial NCT00942019: Study of Bronchial Inflammation in Adolescent Smokers With and Without Obesity
Official title: Bronchial Inflammation in Adolescent Smokers With and Without Obesity
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Obesity
Tobacco Smoking
Keywords: BMI
obesity
CO
tobacco smoking
adolescents
Lead sponsor: Johann Wolfgang Goethe University Hospital
Sponsor class: OTHER
First posted: 2009-07-20
Enrollment: 110
Sex: ALL
Minimum age (years): 14
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Youth

Brief summary: The investigators want to assess differences in lung function and bronchial inflammation of young smokers and non-smokers with (BMI \> 30) and without obesity (BMI \< 25)(4 patient groups). The aim of the study is to compare differences in lung function (VC, FEV1, VC/FEV1, metacholine challenge) and bronchial inflammation in relation with smoking history and levels of exhaled CO. For the latter the investigators will analyze the levels of IL-8, IL-6, TNF alpha and INF gamma and mRNA of LBP, TLR2 and TLR4 in sputum. Further, inflammatory markers e.g. low CRP and inflammatory cytokines levels in the blood will be investigated. The aim is to describe a early stage of chronic obstructive pulmonary disease caused by cigarette smoke in juvenile smokers, and the relationship between bronchial inflammation and obesity in adolescents.

Detailed description: Tobacco smoke is the crucial factor at the beginning and in the course of the bronchial inflammation leading to COPD. It has been shown that cigarette smoke in vitro leads to a MAP kinase and NF-κB-dependent increase of pro-inflammatory cytokines, and inhibits bacteria-induced expression of β-defensins. Several studies revealed an increase of inflammatory cytokines like IL-8 and TNF in the sputum of smokers. Further studies demonstrated an up regulation of LTB4 and LBP possibly due to the LPS derived from tobacco smoke. Hasday et al could show that up to 15 ng per cigarette LPS is released. In principle, the cigarette smoke exposure liked a mild LPS inhalation. In separate work, we could show that LPS inhalation in healthy non-smokers to an increase of CRP and LBP concentrations in the serum lead. In another study of adolescents, 24 smokers (age 17.7 years) and 24 non-smoking (age 17.5 years) were compared. The CO in smokers was significantly increased, and the NO concentrations decreased. At the same time there was a significantly greater bronchial hyperreagibility in the smoker group.

According to a recent study in Germany (KiGGS study), already 31% of the adolescents' boys and 32% of the girls do smoke. The social status is of great importance. Boys and girls from families with a low social status smoke more frequently than those from families with middle-and especially with higher social status. Similarly obesity is linked to the social status with overweight occurring more often in families with a lower social status.

A visceral obesity is closely associated with the risk of type-2-diabetes as well as other aspects of the metabolic syndrome. However, the existing insulin resistance is of fundamental importance. Due to increased visceral fat depots and subsequently increased release of proinflammatory proteins various complications do occur.

Eligibility criteria: Inclusion Criteria:

* informed consent
* age between 14 and 22 years
* smokers CO ≥ 15 ppm
* non-smokers CO ≤ 6 ppm

Exclusion Criteria:

* Asthma \> GINA I°
* others chronic diseases or infections (e.x. HIV, tuberculosis, malignancy)
* pregnancy
* therapy with systemic corticosteroids
* permanent treatment with inhaled corticosteroids
* documented alcohol, substance, and/or drug abuse
* incapability to perform all study procedure

Primary outcomes:
measure: Bronchial inflammatory in adolescents smokers with and without obesity
timeFrame: one day
Secondary outcomes:
measure: Association of bronchial inflammatory parameters in sputum and in the blood
timeFrame: one day
Other outcomes:
Locations:
city: Frankfurt/Main
country: Germany
facility: Children's Hospital, Goethe-University
Study officials:
affiliation: Children´s Hospital, Goethe-University, Frankfurt, Germany
name: Stefan Zielen, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Karimi K, Sarir H, Mortaz E, Smit JJ, Hosseini H, De Kimpe SJ, Nijkamp FP, Folkerts G. Toll-like receptor-4 mediates cigarette smoke-induced cytokine production by human macrophages. Respir Res. 2006 Apr 19;7(1):66. doi: 10.1186/1465-9921-7-66.
citation: Carpagnano GE, Kharitonov SA, Foschino-Barbaro MP, Resta O, Gramiccioni E, Barnes PJ. Increased inflammatory markers in the exhaled breath condensate of cigarette smokers. Eur Respir J. 2003 Apr;21(4):589-93. doi: 10.1183/09031936.03.00022203.
citation: Garey KW, Neuhauser MM, Robbins RA, Danziger LH, Rubinstein I. Markers of inflammation in exhaled breath condensate of young healthy smokers. Chest. 2004 Jan;125(1):22-6. doi: 10.1378/chest.125.1.22.
citation: Csoma Z, Kharitonov SA, Balint B, Bush A, Wilson NM, Barnes PJ. Increased leukotrienes in exhaled breath condensate in childhood asthma. Am J Respir Crit Care Med. 2002 Nov 15;166(10):1345-9. doi: 10.1164/rccm.200203-233OC. Epub 2002 Sep 5.
citation: Sebastian A, Pehrson C, Larsson L. Elevated concentrations of endotoxin in indoor air due to cigarette smoking. J Environ Monit. 2006 May;8(5):519-22. doi: 10.1039/b600706f. Epub 2006 Mar 27.
citation: Kitz R, Rose MA, Borgmann A, Schubert R, Zielen S. Systemic and bronchial inflammation following LPS inhalation in asthmatic and healthy subjects. J Endotoxin Res. 2006;12(6):367-74. doi: 10.1179/096805106X153934.
citation: KiGGS Study of Robert Koch Institut
citation: Kornmann O et al. Influence of second hand tobacco smoke exposure on inflammatory parameters in induced sputum Abstract ATS 2008