Rahul Sangani

Metals in air pollution particles decrease whole-blood coagulation time.

The mechanism underlying procoagulative effects of air pollution particle exposure is not known. The authors tested the postulate that (1) the water-soluble components of an air pollution particle could affect whole-blood coagulation time and (2) metals included in this fraction were responsible for this effect. Exposure to the water-soluble fraction of particulate matter (PM), at doses as low as 50 ng/ml original particle, significantly diminished the whole-blood coagulation time. Inclusion of deferoxamine prolonged coagulation time following the exposures to the water-soluble fraction, whereas equivalent doses of ferroxamine had no effect. Except for nickel, all metal sulfates shortened the whole-blood coagulation time. Iron and zinc were two metals with the greatest capacity to reduce the coagulation time, with an effect observed at 10 ng/ml. Finally, in contrast to the anticoagulants citrate and EDTA, their iron complexes were found to be procoagulative. The authors conclude that metals in the water-soluble fraction of air pollution particles decrease whole-blood coagulation time. These metals can potentially contribute to procoagulative effects observed following human exposures to air pollution particles.

Lung injury after cigarette smoking is particle related

The specific component responsible and the mechanistic pathway for increased human morbidity and mortality after cigarette smoking are yet to be delineated. We propose that 1) injury and disease following cigarette smoking are associated with exposure to and retention of particles produced during smoking and 2) the biological effects of particles associated with cigarette smoking share a single mechanism of injury with all particles. Smoking one cigarette exposes the human respiratory tract to between 15,000 and 40,000 μg particulate matter; this is a carbonaceous product of an incomplete combustion. There are numerous human exposures to other particles, and these vary widely in composition, absolute magnitude, and size of the particle. Individuals exposed to all these particles share a common clinical presentation with a loss of pulmonary function, increased bronchial hyperresponsiveness, pathologic changes of emphysema and fibrosis, and comorbidities, including cardiovascular disease, cerebrovascular disease, peripheral vascular disease, and cancers. Mechanistically, all particle exposures produce an oxidative stress, which is associated with a series of reactions, including an activation of kinase cascades and transcription factors, release of inflammatory mediators, and apoptosis. If disease associated with cigarette smoking is recognized to be particle related, then certain aspects of the clinical presentation can be predicted; this would include worsening of pulmonary function and progression of pathological changes and comorbidity (eg, emphysema and carcinogenesis) after smoking cessation since the particle is retained in the lung and the exposure continues.

Iron, Human Growth, and the Global Epidemic of Obesity

Iron is an essential nutrient utilized in almost every aspect of cell function and its availability has previously limited life. Those same properties which allow iron to function as a catalyst in the reactions of life also present a threat via generation of oxygen-based free radicals. Accordingly; life exists at the interface of iron-deficiency and iron-sufficiency. We propose that: (1) human life is no longer positioned at the limits of iron availability following several decades of fortification and supplementation and there is now an overabundance of the metal among individuals of many societies; (2) this increased iron availability exerts a positive effect on growth by targeting molecules critical in regulating the progression of the cell cycle; there is increased growth in humans provided greater amounts of this metal; and indices of obesity can positively correlate with body stores of iron; and (3) diseases of obesity reflect this over-abundance of iron. Testing potential associations between iron availability and both obesity and obesity-related diseases in populations will be difficult since fortification and supplementation is so extensively practiced.

Derivation and Validation of a Prognostic Model to Predict 6-Month Mortality in an Intensive Care Unit Population

Rationale: Identification of terminally ill patients in the intensive care unit (ICU) would facilitate decision making and timely palliative care. Objectives: To develop and validate a patient‐specific integrated prognostic model to predict 6‐month mortality in medical ICU patients. Methods: A longitudinal prospective cohort study of temporally split samples of 1,049 consecutive medical ICU patients in a tertiary care hospital was performed. For each patient, we collected demographic data, Acute Physiology and Chronic Health Evaluation III score, Charlson comorbidity index, intensivist response to a surprise question (SQ; “Would I be surprised if this patient died in the next 6 months?”) on admission, and vital status at 6 months. Results: Between November 2013 and May 2015, derivation and validation cohorts of 500 and 549 consecutive patients were studied to develop a multivariate logistic regression model. In the multivariate logistic regression model, Charlson comorbidity index (P = 0.033), Acute Physiology and Chronic Health Evaluation III score (P < 0.001), and SQ response (P < 0.001) were predictors of vital status at 6 months. The odds of dying within 6 months were significantly higher when the SQ was answered “no” than when it was answered “yes” (odds ratio, 7.29; P < 0.001). The c‐statistic for the derivation and validation cohorts were 0.832 (95% confidence interval, 0.795‐0.870) and 0.84 (95% confidence interval, 0.806‐0.875), respectively. Conclusions: Our integrated prognostic model, which includes the SQ, has strong discrimination and calibration to predict 6‐month mortality in medical ICU patients. This model can aid clinicians in identifying ICU patients who may benefit from the integration of palliative care into their treatment.

MRT letter: Auto‐fluorescence by human alveolar macrophages after in vitro exposure to air pollution particles

Macrophages from smokers demonstrate an increased auto‐fluorescence. Similarly, auto‐fluorescence follows in vitro exposure of macrophages to cigarette smoke condensate (i.e., the particulate fraction of cigarette smoke). The composition of particles in cigarette smoke can be comparable to air pollution particles. We tested the postulate that macrophages exposed to air pollution particles could demonstrate auto‐fluorescence. Healthy nonsmoking and healthy smoking volunteers (both 18–40 years of age) underwent fiberoptic bronchoscopy with bronchoalveolar lavage and alveolar macrophages isolated. Macrophages were incubated at 37°C in 5% CO2 with either PBS or 100 μg/mL particle for both 1 and 24 h. Particles included a residual oil fly ash, Mt. St. Helens volcanic ash, and ambient air particles collected from St. Louis, Missouri and Salt Lake City, Utah. At the end of incubation, 50 μL of the cell suspension was cytocentrifuged and examined at modes for viewing fluorescein isothiocyanate (FITC) and rhodamine fluorescence. Both emission source air pollution particles demonstrated FITC and rhodamine auto‐fluorescence at 1 and 24 h, but the signal following incubation of the macrophages with oil fly ash appeared greater. Similarly, the ambient particles were associated with auto‐fluorescence by the alveolar macrophages and this appeared to be dose‐dependent. We conclude that exposure of macrophages to air pollution particles can be associated with auto‐fluorescence in the FITC and rhodamine modes. Microsc. Res. Tech., 2010.

Echocardiography-Defined Pulmonary Hypertension in Multiple Myeloma: Risk Factors and Impact on Outcomes.

Objectives Survival of patients with multiple myeloma (MM) has improved as a result of therapeutic advances. There is evidence that some patients with MM develop pulmonary hypertension (PH). The objective of this study was to identify risk factors of echocardiographic PH and its impact on outcomes of patients with MM. Methods We conducted a retrospective study of patients with MM (N = 359) diagnosed between 2000 and 2011 within the Geisinger Medical Center. Chart review was conducted on the subgroup of patients who underwent a transthoracic echocardiogram within 2 years of being diagnosed as having MM. Results A total of 34% of patients (N = 123/359) underwent transthoracic echocardiogram and 32% (N = 39/123) had echocardiography-defined PH. PH was significantly associated with older age (70.5 vs 65.3 years; P = 0.019), greater left atrial diameter (4.0 vs 3.7 cm; P = 0.025), and a trend toward decreased renal function. PH was not associated with myeloma-specific features. Fewer patients with PH underwent hematopoietic stem cell transplantation compared with those without PH (10% vs 30%; P = 0.018). There was no significant difference in survival between the PH and non-PH groups (P = 0.2775). Conclusions Echocardiography-defined PH was found in a sizeable minority of our MM cohort. Although the specific etiology of PH can be determined only through a prospective clinical evaluation, including right heart catheterization, our results suggest that PH in patients with MM is secondary to left heart disease and perhaps impaired renal function. Patients with PH were significantly less likely to undergo hematopoietic stem cell transplantation. Future studies should assess the etiology of PH, its impact on treatment decisions, and prognosis of patients with MM.

Pleural plaques in smoking-associated fibrosis and pulmonary asbestosis

Dear editor Bledsoe et al presents an interesting study examining the disparities between radiologic and pathologic diagnoses of asbestosis in cases referred for consultation in pulmonary malignancy.1 The authors conclude that the clinical diagnosis of asbestosis cannot be reliably distinguished from interstitial fibrosis in heavy smokers. These findings highlight the confounding role of cigarette smoking in the diagnosis of asbestosis when it is based on non-pathologic criteria. Clinical and radiographic characteristics of lung injury following particle exposure (including fibers in which one diameter of the particle is 3× that of the other by definition) are often comparable.2 The results of this investigation1 support further evaluation of a role for cigarette smoking in interstitial fibrosis. Furthermore, asbestos exposure can cause several non-malignant diseases of the pleura and lungs (ie, pleural effusions, pleural plaques, diffuse pleural fibrosis, rounded atelectasis, and asbestosis). Malignancies are also associated with asbestos exposure (ie, lung and laryngeal cancers and mesothelioma).3,4 Relationships between the dose–response and prevalence of asbestos-related diseases are complex.3,5 The injury requiring the least exposure, and which accordingly demonstrates the highest prevalence, is pleural plaque; 80% of individuals significantly exposed to asbestos (total dose of 0.1 fiber-year or less) will have plaques on the chest X-ray while only 0.5%–8% of an unexposed population will reveal such findings.6 Mesothelioma impacts 2,500 to 3,000 workers annually in the United States and its risk is elevated at a total asbestos dose of between 0.1 and 1.0 fiber-year. Those diseases requiring the greatest asbestos exposure are lung cancer and asbestosis; the risk for both is considered elevated at approximately 25 fiber-years. Bledsoe et al identify 24 cases with International Labour Organization (ILO) profusion score of ≥1, out of which only six cases show histological evidence of asbestosis. Of the remaining 18 cases, 16 are identified to have significant smoking history whereas two subjects had unknown smoking status. They observe radiographic evidence of pleural plaques in 82 (44%) of the cases included in the study. It would strengthen the conclusions of the study to know if those diagnosed with asbestosis demonstrated a higher prevalence of pleural plaques than those with cigarette smoking-related fibrosis.1