Screening tests are widely used in medicine to assess the likelihood that members of a defined population have a particular disease. This article presents an overview of such tests including the definitions of key technical (sensitivity and specificity) and population characteristics necessary to assess the benefits and limitations of such tests. Several examples are used to illustrate calculations, including the characteristics of low dose computed tomography as a lung cancer screen, choice of an optimal PSA cutoff and selection of the population to undergo mammography. The importance of careful consideration of the consequences of both false positives and negatives is highlighted. Receiver operating characteristic curves are explained as is the need to carefully select the population group to be tested.

Ultrafine particles (diameter < 100 nm) may be important in the health effects of air pollution, in part because of their predicted high respiratory deposition. However, there are few measurements of ultrafine particle deposition during spontaneous breathing. The fractional deposition for the total respiratory tract of ultrafine carbon particles (count median diameter = 26 nm, geometric standard deviation = 1.6) was measured in 12 healthy subjects (6 female, 6 male) at rest (minute ventilation 9.0 +/- 1.3 L/min) using a mouthpiece exposure system. The mean +/- SD fractional deposition was 0.66 +/- 0.11 by particle number and 0.58 +/- 0.13 by particle mass concentration, similar to model predictions. The number deposition fraction increased as particle size decreased, reaching 0.80 +/- 0.09 for the smallest particles (midpoint count median diameter = 8.7 nm). No gender differences were observed. In an additional 7 subjects (2 female, 5 male) alternating rest with moderate exercise (minute ventilation 38.1 +/- 9.5 L/min), the deposition fraction during exercise increased to 0.83 +/- 0.04 and 0.76 +/- 0.06 by particle number and mass concentration, respectively, and reached 0.94 +/- 0.02 for the smallest particles. Experimental deposition data exceeded model predictions during exercise. The total number of deposited particles was more than 4.5-fold higher during exercise than at rest because of the combined increase in deposition fraction and minute ventilation. Fractional deposition of ultrafine particles during mouth breathing is high in healthy subjects, and increases further with exercise.

BackgroundWe and others have shown that increases in particulate air pollutant (PM) concentrations in the previous hours and days have been associated with increased risks of myocardial infarction, but little is known about the relationships between air pollution and specific subsets of myocardial infarction, such as ST-elevation myocardial infarction (STEMI) and non ST-elevation myocardial infarction (NSTEMI).MethodsUsing data from acute coronary syndrome patients with STEMI (n = 338) and NSTEMI (n = 339) and case-crossover methods, we estimated the risk of STEMI and NSTEMI associated with increased ambient fine particle (<2.5 um) concentrations, ultrafine particle (10-100 nm) number concentrations, and accumulation mode particle (100-500 nm) number concentrations in the previous few hours and days.ResultsWe found a significant 18% increase in the risk of STEMI associated with each 7.1 μg/m3 increase in PM2.5 concentration in the previous hour prior to acute coronary syndrome onset, with smaller, non-significantly increased risks associated with increased fine particle concentrations in the previous 3, 12, and 24 hours. We found no pattern with NSTEMI. Estimates of the risk of STEMI associated with interquartile range increases in ultrafine particle and accumulation mode particle number concentrations in the previous 1 to 96 hours were all greater than 1.0, but not statistically significant. Patients with pre-existing hypertension had a significantly greater risk of STEMI associated with increased fine particle concentration in the previous hour than patients without hypertension.ConclusionsIncreased fine particle concentrations in the hour prior to acute coronary syndrome onset were associated with an increased risk of STEMI, but not NSTEMI. Patients with pre-existing hypertension and other cardiovascular disease appeared particularly susceptible. Further investigation into mechanisms by which PM can preferentially trigger STEMI over NSTEMI within this rapid time scale is needed.

Ambient air particles in the ultrafine size range (diameter < 100 nm) may contribute to the health effects of particulate matter. However, there are few data on ultrafine particle deposition during spontaneous breathing, and none in people with asthma. Sixteen subjects with mild to moderate asthma were exposed for 2 hr, by mouthpiece, to ultrafine carbon particles with a count median diameter (CMD) of 23 nm and a geometric standard deviation of 1.6. Deposition was measured during spontaneous breathing at rest (minute ventilation, 13.3 ± 2.0 L/min) and exercise (minute ventilation, 41.9 ± 9.0 L/min). The mean ± SD fractional deposition was 0.76 ± 0.05 by particle number and 0.69 ± 0.07 by particle mass concentration. The number deposition fraction increased as particle size decreased, reaching 0.84 ± 0.03 for the smallest particles (midpoint CMD = 8.7 nm). No differences between sexes were observed. The deposition fraction increased during exercise to 0.86 ± 0.04 and 0.79 ± 0.05 by particle number and mass concentration, respectively, and reached 0.93 ± 0.02 for the smallest particles. Experimental deposition data exceeded model predictions during exercise. The deposition at rest was greater in these subjects with asthma than in previously studied healthy subjects (0.76 ± 0.05 vs. 0.65 ± 0.10, p < 0.001). The efficient respiratory deposition of ultrafine particles increases further in subjects with asthma.

Human airways produce nitric oxide (NO), and exhaled NO increases as expiratory flow rates fall. We show that mixing during exhalation between the NO produced by the lower, alveolar airways (VL(NO)) and the upper conducting airways (VU(NO)) explains this phenomenon and permits measurement of VL(NO), VU(NO), and the NO diffusing capacity of the conducting airways (DU(NO)). After breath holding for 10-15 s the partial pressure of alveolar NO (PA) becomes constant, and during a subsequent exhalation at a constant expiratory flow rate the alveoli will deliver a stable amount of NO to the conducting airways. The conducting airways secrete NO into the lumen (VU(NO)), which mixes with PA during exhalation, resulting in the observed expiratory concentration of NO (PE). At fast exhalations, PA makes a large contribution to PE, and, at slow exhalations, NO from the conducting airways predominates. Simple equations describing this mixing, combined with measurements of PE at several different expiratory flow rates, permit calculation of PA, VU(NO), and DU(NO). VL(NO) is the product of PA and the alveolar airway diffusion capacity for NO. In seven normal subjects, PA = 1.6 +/- 0.7 x 10(-6) (SD) Torr, VL(NO) = 0.19 +/- 0.07 microl/min, VU(NO) = 0.08 +/- 0.05 microl/min, and DU(NO) = 0.4 +/- 0.4 ml. min(-1). Torr(-1). These quantitative measurements of VL(NO) and VU(NO) are suitable for exploring alterations in NO production at these sites by diseases and physiological stresses.