Background Low serum levels of the anti-inflammatory club cell secretory protein (CC16) have been associated with an accelerated FEV1 decline in COPD. Whether low circulating CC16 precedes lung function deficits and incidence of COPD in the general population is unknown. Methods We used longitudinal data from adults who were COPD-free at baseline from the population-based TESAOD (N=960, mean follow-up: 14yrs), ECRHS-Sp (N=514, 11yrs) and SAPALDIA (N=167, 8yrs) studies. CC16 was measured in serum from baseline and associated with subsequent FEV1 decline and incidence of airflow limitation. To evaluate early life CC16 effects, we also measured circulating CC16 in samples from ages 4-6yrs to predict subsequent lung function in childhood in the CRS (N=427), MAAS (N=481), and BAMSE (N=231) birth cohorts. Findings In adults – after adjustment for sex, age, height, smoking status/intensity, pack-years, asthma, and initial FEV1 levels – baseline CC16 was inversely associated with subsequent decline of FEV1 in TESAOD (p=0.0014), ECRHS-Sp (p=0.023), and a similar trend was found in SAPALDIA (p=0.052). Low CC16 at baseline also predicted an increased risk for incident stage 2 airflow limitation (i.e., FEV1/FVC<70% plus FEV1 % predicted < 80%) in TESAOD and ECRHS-Sp. In children, the lowest tertile of CC16 at age 4–6yrs was associated with subsequent FEV1 deficits up to age 16yrs (meta-analyzed estimate from adjusted models on birth cohorts: −68ml, p=0.0001). Results were confirmed among subjects who never smoked by age 16yrs (−71ml, p<0.0001). Interpretation Low serum CC16 is associated with subsequent slower growth and accelerated decline of lung function, and increased risk of developing stage 2 airflow limitation. Funding US National Heart, Lung, and Blood Institute and EU Seventh Framework Programme. For a complete list of other funding agencies, please refer to the acknowledgements section of the paper.

Does ongoing exposure to political violence prompt subject groups to support or oppose compromise in situations of intractable conflict? If so, what is the mechanism underlying these processes? Political scholarship neither offers conclusive arguments nor sufficiently addresses individual-level forms of exposure to violence in the context of political conflict, particularly the factors mediating political outcomes. We address this by looking at the impact of exposure to political violence, psychological distress, perceived threat, and ethos of conflict on support for political compromise. A mediated model is hypothesized whereby exposure to political violence provokes support for the ethos of conflict and hinders support for compromise through perceived psychological distress and perceived national threat. We examined representative samples of two parties to the same conflict: Israelis (N ¼ 781) and Palestinians from Gaza, East Jerusalem, and the West Bank (N ¼ 1,196). The study's main conclusion is that ethos of conflict serves as a mediating variable in the

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