Taina K. Lajunen, Jouni J. K. Jaakkola, and Maritta S. Jaakkola Am J Respir Crit Care Med Vol 188, Issue 7, Oct 1, 2013 호흡기내과 R2 김다래 / 장나은선생님

 Asthma  chronic inflammation in the airways and episodic airway obstruction  Both a genetic component and environmental exposures seem to play a role for asthma  but these have been studied so far separately and only recently has research started to address potential interaction between such determinants  From the biologic plausibility point of view such interactions are likely to be of major importance for the etiology of asthma, but have so far been studied mainly in childhood-onset asthma.

 There is increasing evidence that second-hand smoke (SHS) exposure increases independently the risk of asthma in children and adults. (30-100%)  According to our systematic literature search, there are no previous studies on the interaction between asthmatic heredity and SHS exposure on the risk of adult-onset asthma.  We have previously shown in this population that SHS exposure at work or at home and asthmatic heredity are independent determinants of adult onset asthma. The objective of this study was to investigate whether asthmatic heredity indicates special susceptibility to the effects of SHS exposure on the risk of adult-onset asthma.

 Study Design  population-based incident case–control study  adults 21 to 63 years of age in Pirkanmaa in South Finland  The population of the area was 447,051 in 2000  Definition and Selection of Cases  all new cases of asthma in 1997–2000 at all healthcare facilities diagnosing asthma in the Pirkanmaa Hospital District  The diagnostic criteria for asthma followed the Finnish National Asthma Guidelines  all cases had asthma diagnosed for the first time at recruitment

 Selection of Control Subjects  A total of 1,016 control subjects participated (response rate, 80%). After excluding those with previous or current asthma (n ¼ 76), those older than 63 years, and those with incomplete questionnaires, our study population included 932 control subjects  Questionnaire  self-administered questionnaire concerning their personal characteristics, health information, family history of asthma and atopic diseases, active smoking and SHS exposure, occupation and work environment, home environment, and diet

 Statistical Methods  The independent and joint effects of asthma heredity categories (parental, maternal, paternal, siblings, and parents and siblings) and SHS exposures (recent: yes or no, and 0, 1–9, or >10 cigarettes/d; lifetime cumulative: 0, 1–99, or >100 cigarette-years) on the risk of adult-onset asthma were studied by comparing the risk of new asthma in the different determinant categories to the reference of “no asthmatic heredity and no SHS exposure.”  Adjustment for sex; age; education; presence of pets in the home; occupational exposure to sensitizers, dusts, and/or fumes; mold problems at home or at work; maternal smoking during pregnancy.  Excess relative risks (ERR) for the independent and joint effects of asthma heredity categories (A) and categories of SHS exposure (B). The departure from additivity of relative risks is quantified by the relative risk due to interaction (RERI), which can be expressed in terms of ERRs as follows:

adjustment ! Excluding ex-smoker current smoker Disease free control group

★ synergism ! RERI = ERR(AB) - ERR(A) - ERR(B) 9.08 = * Parental asthma and SHS exposure in the past 12 months

★ synergism ! * Parental asthma and cumulative SHS exposure RERI = ERR(AB) - ERR(A) - ERR(B) 6.17 = ★ synergism !

* Parental, Sibling asthma and SHS exposure

* Parental, Sibling asthma and cumulative SHS exposure

 This large population-based study shows for the first time that asthmatic heredity and SHS exposure at home and/or work interact so that in combination they have a remarkable synergistic effect on the development of adult asthma.  Such synergism was detected consistently across different heredity groups and types of SHS exposure, which also points toward true biologic interaction.  High estimates of RERI were seen especially for recent SHS exposure and parental asthma, siblings’ asthma, and parental and siblings’ asthma.  Such synergistic effect followed a dose-dependent pattern with recent SHS, so that the higher exposure level (>10 cigarettes/d) showed stronger synergistic effects than the lower exposure level. This implies that those with hereditary constitution for asthma are especially susceptible to develop personal asthma in relation to recent SHS exposure and that this group should be identified and targeted for strong preventive actions.

 Synergistic effect of the recent SHS exposure  maternal asthma >> paternal asthma  The higher susceptibility to SHS associated with maternal asthma could be linked to some in utero exposures or developmental factors.  A high RERI was also seen between recent SHS exposure and both parents having asthma.  both parents and siblings having asthma >> parental asthma siblings’ asthma  Parental asthma also showed synergistic effects with lifetime cumulative SHS exposure(100 cigarette-years), but No interaction was seen between parental asthma and the lower exposure of 1–99 cigarette-years  the exposure patterns of individuals in this category were quite heterogeneous in terms of the amount and duration of exposure.

 According to a systematic literature search, no previous study has investigated potential interaction between asthmatic heredity and SHS exposure on the risk of adult- onset asthma.  One cross-sectional study from Sweden (20) addressed interaction between family history of asthma and childhood SHS on the risk of prevalent asthma in subjects 15–69 years old, but they did not study adult-onset asthma. They found among never-smokers childhood SHS exposure to be a significant risk factor for ever asthma in those without, but not in those with family history of asthma.

 In contrast, our findings show strong synergistic effect between asthmatic heredity and SHS exposure on adult- onset asthma.  There are several differences between these studies that are likely explanations for these different results.  Larsson and coworkers investigated the effect of childhood SHS exposure, whereas we had information on both recent (adulthood) and person’s cumulative lifetime exposure, and for adult-onset asthma SHS exposure during adulthood is probably more important.  In addition, the outcome of the Swedish study was ever asthma based on questionnaire and they reported no information on the timing of SHS exposure in relation to the onset of asthma, whereas we focused on clinically defined incident adult-onset asthma.  The Swedish study did not quantify the SHS exposure.

 Our systematic literature search revealed also that there are no studies of gene or genome-wide interaction with SHS on adult-onset asthma.  Avoiding SHS exposure may prevent onset of asthma especially among those who carry such susceptibility genes. Family history of asthma does not give detailed information on specific genes, but instead represents the person’s asthma susceptibility on the whole genome level. It is easy to define by asking the person about it, which makes it a useful tool in clinical and preventive settings.

 Avoiding SHS exposure could be an important preventive measure for reducing the risk of adult-onset asthma among those who have asthmatic heredity.  Asking about family history of asthma is likely to be a useful tool to identify these susceptible individuals in clinical and preventive settings.

 The first study showing that individuals with asthmatic heredity have a considerably increased risk of adult-onset asthma when exposed to second-hand smoke(SHS).  SHS exposure has dose-dependent synergism with family history of asthma, the joint effect being stronger with higher exposure levels.  Avoiding SHS could be an important preventive measure for reducing the risk of adult-onset asthma among those with asthmatic heredity.  Asking about family history of asthma is a useful tool for identifying these susceptible individuals in clinical and preventive settings.