High rates of respiratory symptoms (14%) and new-onset asthma in previously healthy soldiers (6.6%) have been reported among military personnel post-deployment to Iraq and Afghanistan. The term Iraq/Afghanistan War-Lung Injury (IAW-LI) is used to describe the constellation of respiratory diseases related to hazards of war, such as exposure to burning trash in burn pits, improvised explosive devices, and sandstorms. Burnpits360.org is a nonprofit civilian website which voluntarily tracks medical symptoms among soldiers post-deployment to the Middle East. Subsequent to initiation of the Burnpits360.org website, the Department of Veterans Affairs started the Airborne Hazards and Open Burn Pit registry. This paper: (a) analyzes the latest 38 patients in the Burnpits360.org registry, validated by DD214 Forms; (b) compares strengths and weaknesses of both registries as outlined at the National Academy of Sciences Institute of Medicine Burn Pits Workshop; (c) further characterizes the spectrum of disease in IAW-LI; (d) describes the risk factors of affected populations; (e) summarizes current practices regarding management of the condition; and (f) defines future research objectives.

Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are both debilitating lung diseases which can lead to hypoxemia and pulmonary hypertension (PH). Nuclear Factor of Activated T-cells (NFAT) is a transcription factor implicated in the etiology of vascular remodeling in hypoxic PH. We have previously shown that mice lacking the ability to generate Vasoactive Intestinal Peptide (VIP) develop spontaneous PH, pulmonary arterial remodeling and lung inflammation. Inhibition of NFAT attenuated PH in these mice suggesting a connection between NFAT and VIP. To test the hypotheses that: 1) VIP inhibits NFAT isoform c3 (NFATc3) activity in pulmonary vascular smooth muscle cells; 2) lung NFATc3 activation is associated with disease severity in IPF and COPD patients, and 3) VIP and NFATc3 expression correlate in lung tissue from IPF and COPD patients. NFAT activity was determined in isolated pulmonary arteries from NFAT-luciferase reporter mice. The % of nuclei with NFAT nuclear accumulation was determined in primary human pulmonary artery smooth muscle cell (PASMC) cultures; in lung airway epithelia and smooth muscle and pulmonary endothelia and smooth muscle from IPF and COPD patients; and in PASMC from mouse lung sections by fluorescence microscopy. Both NFAT and VIP mRNA levels were measured in lungs from IPF and COPD patients. Empirical strategies applied to test hypotheses regarding VIP, NFATc3 expression and activity, and disease type and severity. This study shows a significant negative correlation between NFAT isoform c3 protein expression levels in PASMC, activity of NFATc3 in pulmonary endothelial cells, expression and activity of NFATc3 in bronchial epithelial cells and lung function in IPF patients, supporting the concept that NFATc3 is activated in the early stages of IPF. We further show that there is a significant positive correlation between NFATc3 mRNA expression and VIP RNA expression only in lungs from IPF patients. In addition, we found that VIP inhibits NFAT nuclear translocation in primary human pulmonary artery smooth muscle cells (PASMC). Early activation of NFATc3 in IPF patients may contribute to disease progression and the increase in VIP expression could be a protective compensatory mechanism.

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INTRODUCTION AND OBJECTIVE:Previous studies suggested that live kidney donors do not have a higher risk of death or endstage kidney disease (ESKD) than the general population. However, recent studies have suggested that screened kidney donors have a higher risk of ESKD than matched healthy controls. Therefore, donor risk is controversial. Furthermore, only a few studies have evaluated long-term renal function after kidney donation. We aimed to evaluate the long-term outcomes including mortality and renal function in Japanese kidney donors.METHODS: We collected the data of 170 living kidney donors (65men, 115 women) who underwent nephrectomy from 1965 to 2012 in our hospital. Median age was 53 years (range, 26-75 years). We evaluated mortality, cause of death, ESKD incidence, and change in renal function. Donor survival rate was compared with the age-and gender-matched expected survival calculated using the mortality data of Japan provided by the National Cancer Center.RESULTS: Medianfollow-up period was 12.6 (2-41) years. Survival analysis showed that157 donors were still alive and 13 (7.6%) were dead. The median interval between donation and death was 9.4 (2.0e32.8) years; median age at death was 70 (41-87) years. The following causes of death were observed: malignancies, 8; cardiovascular disease, 1; pneumonia, 1; suicide, 1; gastrointestinal bleeding, 1; and sudden death 1. Actual donor survival rates at 5, 10, 20, and 30 years were 98.3%, 94.6%, 93.0%, and 82.5% respectively; these values were comparable to age-and gender-matched expected survival (Fig. 1). Only 1 (0.5%) donor developed ESKD 24 years after donation due to contrast-induced nephropathy after undergoing coronary angiography. Next, we evaluated the renal function in 130 donors. During follow-up, donors showed the following estimated glomerular filtration rates (eGFR): 127 (97.6%), eGFR > 30ml/min; 114 (87.7%), eGFR > 45 ml/min;and 41 (32%), eGFR > 60 ml/min. The percentage of donors with eGFR > 45 ml/minat 5, 10, 20, and 30 years were 98.4%, 95.9%, 80.0%, and 80.0% respectively (Fig. 2).CONCLUSIONS: Our data suggested that kidney donors did not have an increased long-term risk of death compared with the general population. However, some donors showed decreased kidney function 10 years after donation. Therefore, long-term follow up of kidney donors is crucial.