Background Compositional differences in bronchial bacterial microbiota have been associated with asthma, but it remains unclear whether the findings are attributable to asthma, to aeroallergen sensitization or to inhaled corticosteroid treatment. Objectives To compare the bronchial bacterial microbiota in adults with steroid-naive atopic asthma (AA), with atopy but no asthma (ANA), and non-atopic healthy subjects (HC), and determine relationships of bronchial microbiota to phenotypic features of asthma. Methods Bacterial communities in protected bronchial brushings from 42 AA, 21 ANA, and 21 HC subjects were profiled by 16S rRNA gene sequencing. Bacterial composition and community-level functions inferred from sequence profiles were analyzed for between-group differences. Associations with clinical and inflammatory variables were examined, including markers of type 2-related inflammation and change in airway hyperresponsiveness following six weeks of fluticasone treatment. Results The bronchial microbiome differed significantly among the three groups. Asthmatic subjects were uniquely enriched in members of the Haemophilus, Neisseria., Fusobacterium, Porphyromonas and Sphingomonodaceae, and depleted in members of the Mogibacteriaceae and Lactobacillales. Asthma-associated differences in predicted bacterial functions included involvement of amino acid and short-chain fatty acid metabolism pathways. Subjects with type 2-high asthma harbored significantly lower bronchial bacterial burden. Distinct changes in specific microbiota members were seen following fluticasone treatment. Steroid-responsiveness was linked to differences in baseline compositional and functional features of the bacterial microbiome. Conclusion Even in mild steroid-naive asthma subjects, differences in the bronchial microbiome are associated with immunologic and clinical features of the disease. The specific differences identified suggest possible microbiome targets for future approaches to asthma treatment or prevention.

BACKGROUND: This study assessed the impact of surgical, histopathologic and patient‐related factors on the risks of local and distant recurrence and overall survival for patients with stages I through IIIA nonsmall cell lung carcinoma (NSCLC) undergoing definitive resection with or without adjuvant chemotherapy. METHODS: This study included 373 consecutive patients treated between 2000 and 2005 who did not receive adjuvant or neoadjuvant radiotherapy, had at least 3 months of follow‐up, and did not have a history of other cancers within 5 years of the diagnosis of their NSCLC. Of these, 52% had pathologic stage IA disease, 30% had stage IB, 5% had stage IIA, 8% had stage IIB and 5% had stage III disease. Forty‐four patients received chemotherapy. RESULTS: The median follow‐up was 33 months. Local failure rates at 2 years, 3 years, and 5 years were 16%, 22%, and 32%, respectively; distant recurrence rates were 13%, 15%, and 21%, respectively. Multivariable analysis revealed that local recurrence was significantly associated with the presence of lymphatic or vascular invasion (LVI), the use of chemotherapy, and having diabetes; distant recurrence was significantly higher in patients with nonsquamous cell histology, those undergoing pneumonectomy, and those with more advanced TNM stage. Survival was significantly associated with age, history of myocardial infarction, performance of a pneumonectomy, histology, LVI, and the number of positive N1 lymph nodes. CONCLUSIONS: Local recurrence was the predominant type of failure in this series. Patient with diabetes or LVI may benefit from close surveillance and aggressive therapy of asymptomatic local recurrences, especially when chemotherapy is given in addition to surgery. Cancer 2009. © 2009 American Cancer Society.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone is a potent and abundant procarcinogen found in tobacco smoke, and glucuronidation of its major metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), by UDP-glucuronosyltransferases (UGT) including UGT2B17 is an important mechanism for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone detoxification. Both copies of the UGT2B17 gene are deleted in f10% of Whites and the deletion is associated with a reduction in NNAL glucuronidation activity in vitro. In this study, we examined the effects of the UGT2B17 deletion (0/0) on NNAL glucuronidation rates in a sample of 82 healthy cigarette smokers and further examined its effects on lung cancer risk in a separate case-control study. In the healthy smokers study, a lower urinary ratio of NNAL-glucuronide to NNAL was observed in women with the UGT2B17 deletion (0/0) as compared with women with either the wild-type or heterozygous genotypes (P = 0.058).There were no significant differences in this ratio by genotype in men (P = 0.597). In the case-control study of 398 lung cancer patients and 697 community controls, the UGT2B17 deletion (0/0) was associated with a significant increase in risk of lung cancer in women (odds ratio, 2.0; 95% confidence interval, 1.01-4.0). The risk for the subset of women with lung adenocarcinoma was 2.8 (95% confidence interval, 1.2-6.3). The deletion was not associated with other lung histologic types in women and was not associated with the risk for any lung histologic types in men. The association of the UGT2B17 deletion with increased lung adenocarcinoma in women is consistent with its association with decreased NNAL glucuronidation rates in women and with studies showing that NNAL is a selective inducer of lung adenocarcinoma in experimental animals. (Cancer Epidemiol Biomarkers Prev 2007;16(4):823 -8)