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The IL-33/ST2 pathway is linked with asthma susceptibility. Inhaled allergens, pollutants, and respiratory viruses, which trigger asthma exacerbations, induce release of IL-33, an epithelial-derived "alarmin." Astegolimab, a human IgG 2 mAb, selectively inhibits the IL-33 receptor, ST2. Approved biologic therapies for severe asthma mainly benefit patients with elevated blood eosinophils (type 2-high), but limited options are available for patients with low blood eosinophils (type 2-low). Inhibiting IL-33 signaling may target pathogenic pathways in a wider spectrum of asthmatics. This study evaluated astegolimab efficacy and safety in patients with severe asthma. This double-blind, placebo-controlled, dose-ranging study (ZENYATTA [A Study to Assess the Efficacy and Safety of MSTT1041A in Participants With Uncontrolled Severe Asthma]) randomized 502 adults with severe asthma to subcutaneous placebo or 70-mg, 210-mg, or 490-mg doses of astegolimab every 4 weeks. The primary endpoint was the annualized asthma exacerbation rate (AER) at week 54. Enrollment caps ensured ∼30 patients who were eosinophil-high (≥300 cells/μL) and ∼95 patients who were eosinophil-low (<300 cells/μL) per arm. Overall, adjusted AER reductions relative to placebo were 43% (P =.005), 22% (P =.18), and 37% (P =.01) for 490-mg, 210-mg, and 70-mg doses of astegolimab, respectively. Adjusted AER reductions for patients who were eosinophil-low were comparable to reductions in the overall population: 54% (P =.002), 14% (P =.48), and 35% (P =.05) for 490-mg, 210-mg, and 70-mg doses of astegolimab. Adverse events were similar in astegolimab- and placebo-treated groups. Astegolimab reduced AER in a broad population of patients, including those who were eosinophil-low, with inadequately controlled, severe asthma. Astegolimab was safe and well tolerated. [Display omitted] [ABSTRACT FROM AUTHOR]

Background The aim of this study is to identify the predictors of hospital readmission or early unplanned return to clinic within 30 days of discharge after pulmonary lobectomy. Methods The medical records of patients undergoing lobectomy by the thoracic surgery service between January 2009 and July 2012 were reviewed. All lobectomies were included irrespective of the etiology of disease. Multivariate logistic regression methods were used to identify predictors of readmission and or early unplanned return to clinic. Results Two hundred thirteen patients underwent a pulmonary lobectomy during the study period (median age, 67 years). Pathologic diagnosis was malignant in 94% of the patients and benign in 6%. Minimally invasive approaches were used in 69% of the patients, whereas open thoracotomy was used in 31%. Median hospital length of stay was 4 days, and postoperative mortality occurred in 1 patient (0.5%). The Charlson comorbidity index was 1 ± 1. Predicted postoperative forced expiratory volume in 1 second and diffusing capacity of the lung for carbon monoxide were 68% ± 18% and 64% ± 17%, respectively. Postoperative complications occurred in 31% of patients; 13% required readmission to the hospital within 30 days of discharge or early unplanned return to clinic. Predictors of readmission or early unplanned return to clinic were unplanned transfer to the intensive care unit (odds ratio, 10.4; 95% confidence interval, 1.1 to 103.5; p = 0.04) and Charlson comorbidity index greater than 0 (odds ratio, 1.5; 95% confidence interval, 1.04 to 2.03; p = 0.03). Readmission or early unplanned return to clinic was independent of surgical approach ( p = 0.32). Conclusions Patients who require a postoperative transfer to the intensive care unit or with higher Charlson comorbidity index are at higher risk for hospital readmission after pulmonary lobectomy. Readmission was not affected by the surgical approach. Whether a different strategy to follow-up for these high-risk patients can prevent readmission remains to be determined. [ABSTRACT FROM AUTHOR]

Background Single nucleotide polymorphisms (SNPs) in the chitinase 3-like 1 ( CHI3L1 ) promoter, the gene encoding YKL-40, are associated with circulating YKL-40 levels and asthma prevalence. However, the effects of gene polymorphisms on asthma severity and airway expression of YKL-40 have not been examined. Objective We sought to determine the effect of genetic variation in CHI3L1 on asthma severity and YKL-40 expression in subjects from the Yale Center for Asthma and Airways Disease and the Severe Asthma Research Program. Methods SNPs spanning the CHI3L1 gene were genotyped in 259 Yale Center for Asthma and Airways Disease and 919 Severe Asthma Research Program subjects. Association and haplotype analyses were conducted to identify effects on airflow obstruction, YKL-40 levels, and asthma severity. Results Fifteen SNPs in CHI3L1 were associated with FEV 1 , serum YKL-40 levels, or both. rs12141494 (intron 6) was the only SNP in subjects of European ancestry in both cohorts that was associated with serum YKL-40 levels and postbronchodilator FEV 1 . Conditional analysis demonstrated that the effect on lung function was independent of the promoter SNP rs4950928, and haplotype analysis demonstrated that G alleles at rs12141494 and rs4950928 are associated with lower YKL-40 expression and higher FEV 1 percent predicted values. In asthmatic subjects the risk allele A at rs12141494 was associated with severe asthma and higher YKL-40 expression in the airway ( P ≤ .05). Conclusion In contrast to the promoter SNP rs4950928, the intronic SNP rs12141494 in CHI3L1 is associated with asthma severity, lung function, and YKL-40 expression in the blood and airway. These data suggest that SNP rs12141494 modulates YKL-40 expression in the airway and contributes to airway remodeling and asthma severity. [ABSTRACT FROM AUTHOR]

Introduction: Electronic cigarettes (ECs) have emerged as a potential harm-reducing alternative for tobacco smokers. However, the role ECs might play in treatment settings is unclear. We conducted an exploratory study of treatment-seeking smokers enrolling in a standard tobacco treatment program who were provided with either a nicotine or non-nicotine EC to use as needed to cease tobacco smoking.Methods: Treatment-seeking smokers received standard tobacco treatment for 8weeks and were given nicotine transdermal patch therapy, behavioral counseling, and either a nicotine or non-nicotine EC to use as needed. Smoking and EC use patterns were tracked longitudinally to week 24.Results: 40 subjects were enrolled into the study. At week 24, 6 subjects (15%) were abstinent, and the mean reduction in reported cigarettes smoked per day was 6.8±12. There were no significant differences in smoking outcomes between those who received a nicotine or non-nicotine EC (proportion abstinent at 24weeks: nicotine EC=4/20 (20%); non-nicotine EC=2/20 (10%); p=0.66). Among subjects assessed at follow-up, 62.5% were EC non-users.Conclusions: The addition of a 2nd generation EC to outpatient tobacco treatment among tobacco smokers is feasible. Among those who quit smoking, half were still using the EC at 6-month follow-up. Appeal of the EC among smokers was variable, and those who had quit smoking tended to switch to lower strength nicotine solutions. Further research is needed to determine whether ECs can reduce harm and be an effective adjunct to existing tobacco treatment interventions. [ABSTRACT FROM AUTHOR]