CD14 is a pattern recognition receptor that plays a central role in innate immunity through recognition of bacterial lipoglycans, primarily LPS. Recently, our group has identified a common single nucleotide polymorphism, −159C→T, in the CD14 proximal promoter. Homozygous carriers of the T allele have a significant increase in soluble CD14, but a decreased total serum IgE. This epidemiologic evidence led us to investigate the molecular basis for the effects of CD14/−159C→T on CD14 regulation in monocytes and hepatocytes, the two major cell types known to express this gene in vivo. EMSA analysis showed that the T allele results in decreased affinity of DNA/protein interactions at a GC box that contains a binding site for Sp1, Sp2, and Sp3 transcription factors. In reporter assays, the transcriptional activity of the T allele was increased in monocytic Mono Mac 6 cells, which express low levels of Sp3, a member of the Sp family with inhibitory potential relative to activating Sp1 and Sp2. By contrast, both alleles were transcribed equivalently in Sp3-rich hepatocytic HepG2 cells. Our data indicate that the interplay between CD14 promoter affinity and the [Sp3]:[Sp1 + Sp2] ratio plays a critical mechanistic role in regulating transcription of the two CD14 alleles. Variation in a key gene of innate immunity may be important for the pathogenesis of allergy and inflammatory disease through gene-by-gene and/or gene-by-environment interactions.

We examined the course and prognosis in subjects selected from the general population who had chronic airflow obstruction at the time of their enrollment in a longitudinal epidemiologic study. Mortality and the rate of change in lung function were analyzed in relation to the initial clinical characteristics of the subjects. Twenty-seven subjects with symptoms and signs of asthma (Group I) had a higher survival rate and a much lower rate of decline in pulmonary function than the 45 subjects in Group III, whose clinical characteristics were more compatible with an emphysematous form of chronic obstructive pulmonary disease (COPD). The 10-year mortality among subjects in Group III (non-atopic smokers without a history of asthma) was close to 60 percent, whereas it was only 15 percent in Group I (atopic subjects or nonsmokers with known asthma). The mean overall rate of decline in forced expiratory volume in one second was 70 ml per year in Group III but less than 5 ml per year in Group I. Forty-five patients (Group II) who did not clearly fit into either Group I or III had intermediate values for survival and decline in pulmonary function. Previous data on mortality from COPD and the rate of progression of the condition, although compatible with our findings in patients who had an emphysematous form of disease, are not applicable to those with an asthmatic-bronchitic form. Better control of the progression of asthmatic bronchitis with therapy may explain its more favorable prognosis.

will be to discover the personality characteristics which make some doctors particularly vulnerable to desynchronisation of circadian performance rhythm after disruption of sleep. Data from the Tucson epidemiological study of airways obstructive disease on smoking of non-tobacco cigarettes such as marijuana were analysed to determine the effect of such smoking on respiratory symptoms and pulmonary function. Among adults aged under 40, 14% had smoked non-tobacco cigarettes at some time and 90/o were current users. The prevalence of respiratory symptoms was increased in smokers of non-tobacco cigarettes. After tobacco smoking had been controiled for men who smoked non-tobacco cigarettes showed significant decreases in expiratory flow rates at low lung volumes and in the ratio of the forced expiratory volume in one second to the vital capacity. This effect on pulmonary function in male non-tobacco cigarette smokers was greater than the effect of tobacco cigarette smoking.These data suggest that non-tobacco cigarette smoking may be an important risk factor in young adults with respiratory symptoms or evidence of airways obstruction.

Data from four consecutive surveys of Tucson longitudinal study of airways obstructive disease were used to examine the relation of respiratory symptoms and pulmonary function to non-tobacco cigarette smoking. The surveys were conducted over a six-year period and provided data on 1802 subjects 15-60 years of age, with a total of 5659 individual questionnaires. Estimated odds ratio (OR) of current non-tobacco smoking for chronic cough was 1.73, for chronic phlegm: 1.53, and for wheeze: 2.01 (p less than 0.05). These estimates were adjusted for age, tobacco smoking and occurrence of the symptom in preceding survey. The increased risk of the symptoms was related to the habit continued for several years, and there was no immediate remission of the symptoms after quitting smoking. A significant (p less than 0.05) reduction in pulmonary function (FEV1, Vmax50 and their ratios with FVC) was found a year or more after current non-tobacco smoking was reported. Although the average consumption of non-tobacco cigarettes, believed to be marijuana smoking, was less than one per day, significant effects were still detectable in both pulmonary function and respiratory symptoms.

IntroductionTracheal intubation in the Intensive Care Unit (ICU) can be challenging as patients often have anatomic and physiologic characteristics that make intubation particularly difficult. Video laryngoscopy (VL) has been shown to improve first attempt success compared to direct laryngoscopy (DL) in many clinical settings and may be an option for ICU intubations.MethodsAll intubations performed in this academic medical ICU during a 13-month period were entered into a prospectively collected quality control database. After each intubation, the operator completed a standardized form evaluating multiple aspects of the intubation including: patient demographics, difficult airway characteristics (DACs), method and device(s) used, medications used, outcomes and complications of each attempt. Primary outcome was first attempt success. Secondary outcomes were grade of laryngoscopic view, ultimate success, esophageal intubations, and desaturation. Multivariate logistic regression was performed for first attempt and ultimate success.ResultsOver the 13-month study period (January 2012-February 2013), a total of 234 patients were intubated using VL and 56 patients were intubated with DL. First attempt success for VL was 184/234 (78.6%; 95% CI 72.8 to 83.7) while DL was 34/56 patients (60.7%; 95% CI 46.8 to 73.5). Ultimate success for VL was 230/234 (98.3%; 95% CI 95.1 to 99.3) while DL was 52/56 patients (91.2%; 95% CI 81.3 to 97.2). In the multivariate regression model, VL was predictive of first attempt success with an odds ratio of 7.67 (95% CI 3.18 to 18.45). VL was predictive of ultimate success with an odds ratio of 15.77 (95% CI 1.92 to 129). Cormack-Lehane I or II view occurred 199/234 times (85.8%; 95% CI 79.5 to 89.1) and a median POGO (Percentage of Glottic Opening) of 82% (IQR 60 to 100) with VL, while Cormack-Lehane I or II view occurred 34/56 times (61.8%; 95% CI 45.7 to 71.9) and a median POGO of 45% (IQR 0 to 78%) with DL. VL reduced the esophageal intubation rate from 12.5% with DL to 1.3% (P = 0.001) but there was no difference in desaturation rates.ConclusionsIn the medical ICU, video laryngoscopy resulted in higher first attempt and ultimate intubation success rates and improved grade of laryngoscopic view while reducing the esophageal intubation rate compared to direct laryngoscopy.