BackgroundSystemic inflammation is associated with reduced lung function in both healthy individuals and those with chronic obstructive pulmonary disease (COPD). Whether systemic inflammation in healthy young adults is associated with future impairment in lung health is uncertain.Methodology/Principal FindingsWe evaluated the association between plasma fibrinogen and C-reactive protein (CRP) in young adults and lung function in the Coronary Artery Risk Development in Young Adults cohort study. Higher year 7 fibrinogen was associated with greater loss of forced vital capacity (FVC) between years 5 and 20 (439 mL in quartile 4 vs. 398 mL in quartile 1, P<0.001) and forced expiratory volume in 1 second (FEV1) (487 mL in quartile 4 vs. 446 mL in quartile 1, P<0.001) independent of cigarette smoking, body habitus, baseline lung function and demographic factors. Higher year 7 CRP was also associated with both greater loss of FVC (455 mL in quartile 4 vs. 390 mL in quartile 1, P<0.001) and FEV1 (491 mL in quartile 4 vs. 442 mL in quartile 1, P = 0.001). Higher year 7 fibrinogen and CRP were associated with abnormal FVC at year 20 (odds ratio (OR) per standard deviation 1.51 (95% confidence interval (CI): 1.30–1.75) for fibrinogen and 1.35 (95% CI: 1.14–1.59) for CRP). Higher year 5 fibrinogen was additionally associated with abnormal FEV1. A positive interaction was observed between pack-years cigarette smoking and year 7 CRP for the COPD endpoint, and among participants with greater than 10 pack-years of cigarette exposure, year 7 CRP was associated with greater odds of COPD at year 20 (OR per standard deviation 1.53 (95% CI: 1.08–2.16).Conclusion/SignificanceSystemic inflammation in young adults is associated with abnormal lung function in middle age. In particular, elevated CRP may identify vulnerability to COPD among individuals who smoke.Trial RegistrationClinicalTrials.gov NCT00005130

Objectives Inflammation in utero is linked to childhood respiratory and infectious complications. Obesity is an increasingly common chronic inflammatory state, yet little is known about its role in childhood respiratory illness. We sought to examine the association between maternal pre-gravid BMI and early childhood respiratory hospitalization. Methods We conducted a population-based case-control study using the Washington State Comprehensive Hospital Abstract Reporting System (CHARS) and linked birth certificate data. Cases were children age 0 to 5 years, born in Washington state, with a respiratory hospitalization between 2003 and 2008. We identified 15,318 cases, frequency matching each case to two controls by birth year (total 31,060 controls). We used logistic regression to estimate the risk (approximated by odds ratios) of early childhood respiratory hospitalization according to maternal pre-gravid body mass index (BMI) category (underweight, normal, overweight, obese), after adjustment for maternal and infant characteristics. Results An elevated maternal pre-gravid BMI was associated with increased risk of childhood respiratory hospitalization, with an adjusted odds ratio OR [95% CI] = 1.08 [1.03–1.14] for overweight mothers (BMI 25–29.9 kg/m2), and OR = 1.29 [1.22–1.36] for obese mothers (BMI ≥ 30 kg/m2). Conclusions An elevated maternal pre-gravid BMI was associated with higher risk of early childhood respiratory hospitalization. Childhood respiratory illness may be an important complication of excess maternal weight that should be shared with expectant mothers.

Older and younger adults with weaker EF tend to consume more high-calorie snack food compared with their stronger EF counterparts. These tendencies appear to be especially amplified in the presence of facilitating cues.

Abnormal lung function is a known risk factor for poor outcomes in the allogeneic hematopoietic stem cell transplant (HSCT) population, although the specific causes of these abnormalities have not been well explored. There is limited data on the effect of cigarette smoking on transplant outcomes. We conducted a retrospective observational cohort study of 845 consecutive patients aged ≥ 18 years who underwent allogeneic HSCT at the Seattle Cancer Care Alliance/Fred Hutchinson Cancer Research Center. Smoking exposure was defined by quit time, smoking status (never, former, and current) and log2-transformed pack-years. The main outcomes were time to respiratory failure within 100 days of transplant, relapse, and non-relapse mortality. In multivariable analyses, a two-fold increase in pack-years smoked was associated with an increased risk of early respiratory failure (HR 1.33, 95% CI 1.09 to 1.64, p = 0.006). This association was observed independent of pre-transplant lung function. A two-fold increase in pack-years smoked was associated with an increased risk of relapse, but this finding was not statistically significant (HR 1.16, 95% CI 0.92 to 1.46, p = 0.21). An association was not observed between cigarette smoking and non-relapse mortality. Cigarette smoking is associated with an increased risk of respiratory failure and relapse within 100 days of allogeneic HSCT. The association with respiratory failure is mediated in part by abnormal lung function prior to transplant and likely through other mechanisms as well. Given the adverse effects associated with cigarette smoking prior to transplant, future studies should focus on obtaining accurate smoking histories, tracking prospective changes in smoking status, and assessing the benefits of tobacco cessation on outcomes in this population.

SUMMARYWe describe a 51-year-old man who developed renal and neural toxicity after the administration of colistin. He developed respiratory apnoea, neuromuscular blockade and severe comatose encephalopathy with the lack of brainstem reflexes. After discontinuation of the antibiotic, he made a prompt recovery to his baseline neurological function. The case illustrates the importance of recognising the toxicities associated with colistin.

The systemic effects of chronic obstructive pulmonary disease (COPD) are becoming increasingly apparent. Systemic inflammatory markers are of interest in mediating these systemic effects, and studies have shown that increased levels of inflammatory markers such as fibrinogen and C-reactive protein are associated not only with COPD severity, but also with the risk of cardiovascular morbidity and mortality. In addition, higher levels of fibrinogen and C-reactive protein are associated with lower lung function in individuals with no evidence of lung disease. Cigarette smoke is traditionally considered to be a risk factor for COPD and a potential stimulus for systemic inflammation, but COPD does not develop in all smokers. As such, other mechanisms are likely involved. Certain individuals may exhibit an "inflammatory phenotype" and have a greater predisposition to mounting an excessive inflammatory response to a certain stimulus. Therapy with inhaled corticosteroids has shown a decrease in systemic markers of inflammation and a trend towards improving lung function and mortality.

No abstract

Objectives Critical illness reduces β-lactam pharmacokinetic/pharmacodynamic (PK/PD) attainment. We sought to quantify PK/PD attainment in patients with hospital-acquired pneumonia. Methods Meropenem plasma PK data (n = 70 patients) were modelled, PK/PD attainment rates were calculated for empirical and definitive targets, and between-patient variability was quantified [as a coefficient of variation (CV%)]. Results Attainment of 100% T&gt;4×MIC was variable for both empirical (CV% = 92) and directed (CV% = 33%) treatment. Conclusions Individualization is required to achieve suggested PK/PD targets in critically ill patients.