Image-based determination of chord lengths in air-dried lungs.

An image-based method was developed in order to determine chord lengths in sections of dog and sheep lungs air-dried at 25 cm H2O transpulmonary pressure. To facilitate image processing, optical contrast in the sections was optimized with respect to section thickness, stain type, stain concentration, staining temperature, staining time and clearing method. Digital processing of images used standard procedures, e.g. thresholding, dilation and thinning, as well as algorithms written to subtract background, delete spots and measure chord lengths. Correlation of image-based vs. manual determination of mean chord length in 17 sections from a sheep lung, stained for optimal contrast yielded an R2 of 0.82 (P < 0.0001). For 95 sections from three dog lungs, stained with lower contrast, R2 was 0.65 (P < 0.0001). Weaker correlations were observed between image-based and manual determinations of the standard deviation, the geometric standard deviation, and the 95th percentile of chord lengths (P < 0.05). The results show that image-based stereology of inflated air-dried lungs can provide valid measures of mean chord length and other statistics of chord length distribution.

Characterization of metalworking fluid aerosols in bearing grinding operations.

The concentrations and size distribution of metalworking fluid aerosols were investigated in grinding operations in the bearing manufacturing industry. Fifteen paired open- and closed-face cassette samples and five cascade impactor samples were obtained in each of three types of grinding machinery (face, microcentric, and progressive). Aerosol mass concentration as measured by open-face filter sampling ranged from 0.34 to 2.43 mg/m3. As measured by closed-face sampling the range was 0.14 to 2.01 mg/m3. For each grinding process, open-face concentration was significantly higher than the closed-face concentration (paired t-test, p <0.05). Mass median aerodynamic diameter (MMAD) ranged from 3.33 to 6.26 microm. The percentage of mass greater than 9 microm ranged from 8.0 to 45.3. The MMAD and fraction greater than 9 microm were significantly greater for the aerosol produced by the face grinder compared with the other two processes. The results indicate that (1) closed-face sampling results in a lower aerosol mass concentration, as compared with open-face sampling, with the degree of difference being somewhat dependent on grinding process; and (2) the particle size distribution and concentration of metalworking fluid aerosols may vary with the type of grinding operation sampled.

Clinical signs, evaluation of bronchoalveolar lavage fluid, and assessment of pulmonary function in horses with inflammatory respiratory disease.

OBJECTIVE: To evaluate the association among clinical signs, results of cytologic evaluation of bronchoalveolar lavage (BAL) fluid, and measures of pulmonary function in horses with inflammatory respiratory disease. ANIMALS: 9 healthy horses, 5 horses with inflammatory airway disease (IAD), and 9 horses with chronic obstructive pulmonary disease (COPD). PROCEDURES: Clinical examination, lung function tests, and BAL were performed on each horse. RESULTS: Standard lung mechanics of horses with exacerbated COPD differed significantly from those of healthy horses; however, there were few differences among horses with IAD, horses with COPD during remission, and healthy horses. Most variables for forced expiration (FE) in horses with COPD or IAD differed significantly from those for healthy horses. Results of clinical examination had low to moderate sensitivity and predictive values for a diagnosis of COPD (range, 67 to 80%). Results of FE tests had high sensitivity, specificity, and predictive values for a diagnosis of COPD (79 to 100%), and results of standard lung mechanics tests had low sensitivity and predictive values (22 to 69%). Percentage of neutrophils in BAL fluid was highly sensitive (100%) but moderately specific (64%) for a diagnosis of COPD. CONCLUSIONS AND CLINICAL RELEVANCE: Clinical examination is moderately accurate for establishing a diagnosis of COPD. Forced expiration tests can specifically detect early signs of airway obstruction in horses with COPD and IAD that may otherwise be inapparent. Cytologic evaluation of BAL fluid allows early detection of inflammatory respiratory disease, but it is not specific for COPD.

Forced expiration: a test for airflow obstruction in horses.

The purpose of this study was to assess whether our method of inducing forced expiration detects small airway obstruction in horses. Parameters derived from forced expiratory flow-volume (FEFV) curves were compared with lung mechanics data obtained during spontaneous breathing in nine healthy horses, in three after histamine challenge, and in two with chronic obstructive pulmonary disease (COPD) pre- and posttherapy with prednisone. Parameters measured in the healthy horses included forced vital capacity (FVC = 41.6 +/- 5.8 liters; means +/- SD) and forced expiratory flow (FEF) at various percentages of FVC (range of 20.4-29.7 l/s). Histamine challenge induced a dose-dependent decrease in FVC and FEF at low lung volume. After therapy, lung function of the two COPD horses improved to a point where one horse had normal lung mechanics during tidal breathing; however, FEF at 95% of FVC (4.9 l/s) was still decreased. We concluded that FEFV curve analysis allowed the detection of induced or naturally occurring airway obstruction.

The distribution of inhaled particles in aerosol measurements of pulmonary airspace size.

When the deposition of aerosol boluses is used to estimate mean pulmonary airspace size, an implicit assumption is made that the inhaled particles are distributed uniformly among normal and diseased lung regions. This assumption was examined in a series of dogs in which emphysema was experimentally induced by exposure to papain. After the experimental disease had developed for several weeks, boluses of fluorescent particles were inhaled, using a breathing pattern similar to that used for aerosol measurements of airspace size. The lungs were then excised and 18-20 tissue blocks were obtained from each lung. A section from each tissue block was analyzed to determine the mean liner intercept (Lm), which was considered as an index of lung injury. In the same sections, the density of particles was determined by counting particles in a number of microscopic fields and dividing the particle count by the number of fields sampled. Correlation analysis generally revealed a negative correlation of particle density with Lm, indicating fewer particles being delivered to diseased regions. One lung, however, showed a positive correlation between particle density and Lm. Correction for the fractional deposition of aerosol in the lung regions weakened but did not reverse the relationship between particle density and Lm. A model calculation of the effect of the observed nonuniform distribution of aerosol on the determination of airspace size found a negligible effect of uneven ventilation on mean airspace size determination in this experimental preparation.

Aerosol measurement of airspace diameter correlates with morphometry in normal and papain-exposed air dried lungs.

Aerosol measures of effective airspace diameter (EAD) were correlated with morphometric parameters in a series of 8 canine lungs, 5 of which had been exposed to papain in order to cause experimental emphysema. In an effort to preserve alveolar dimensions without shrinkage, the lungs were fixed by air drying at total lung capacity. EAD was measured with 400-cm2 boluses, with mean penetration index (Pen), defined as volumetric bolus penetration/total lung capacity, equal to 0.34 (EAD400), and with 800-cm2 aerosol boluses, with mean Pen equal to 0.59 (EADdeep). Morphometric analysis, following measurement of EADs, determined the mean linear intercept and other parameters of the chordlength distribution, including the 90th, 95th, and 99th percentiles (p90, p95, p99), the standard deviation, and the geometric standard deviation (GSD). EAD400 was significantly correlated with Lm (r2 = .68, P < .05), p95, (r2 = .85, P < .01), p99 (r2 = .94, P < .001), and GSD (r2 = .94, P < .001). Similar results were found with EADdeep. In general, correlations were stronger between EAD and p95, p99, or GSD than between EAD and Lm. A comparison with a previous similar study relating EAD to morphometry in a series of lungs fixed by formalin fixation found closer agreement between EAD and morphometry when lungs were fixed by air drying. Overall, the data support the validity of EAD as an in vivo method of determining airspace size at total lung capacity.

Aerosol probes of lung injury in a 28-wk longitudinal study of mild experimental emphysema in dogs.

After baseline measurements of lung mechanics, effective air space diameter (EAD), and aerosol dispersion (AD), three dogs were exposed to two treatments of aerosolized papain (3 ml of a 4% solution), and measurements were repeated during a 28-wk follow-up period. EAD and AD were measured with boluses of 0.7-micrometer particles of di-2-ethylhexl sebacate, with Pen (i.e., volumetric bolus penetration/total lung capacity) between 0.1 and 0.4. After papain exposure, EAD increased a mean of 28% (P < 0.0001) and AD (Pen = 0.3, 0.4) increased 4-7% (P < 0.03). The progression of injury was indicated by increasing trends in total lung capacity (P < 0.05), residual volume (P < 0.05), and EAD (P = 0.06) through week 18. There was no evidence of disease progression between weeks 18 and 28, whereas some of the data for individual dogs suggested partial recovery from lung injury at week 28. The results show that aerosol probes can detect and characterize mild lung injury in experimental emphysema.

The size distribution of droplets in the exhaled breath of healthy human subjects.

Droplets carried in exhaled breath may carry microorganisms capable of transmitting disease over both short and long distances. The size distribution of such droplets will influence the type of organisms that may be carried as well as strategies for controlling airborne infection. The aim of this study was to characterize the size distribution of droplets exhaled by healthy individuals. Exhaled droplets from human subjects performing four respiratory actions (mouth breathing, nose breathing, coughing, talking) were measured by both an optical particle counter (OPC) and an analytical transmission electron microscope (AEM). The OPC indicated a preponderance of particles less than 1 mu, although larger particles were also found. Measurements with the AEM confirmed the existence of larger sized droplets in the exhaled breath. In general, coughing produced the largest droplet concentrations and nose breathing the least, although considerable intersubject variability was observed.

A servo-controlled respiration system for inhalation studies in anesthetized animals.

To facilitate aerosol deposition experiments and aerosol exposures in anesthetized animals, a servo-controlled respiration system was developed and tested. The system induces ventilation by varying extrathoracic pressure in a whole body respiratory in which an intubated animal is placed. The pressure inside the whole body respirator is varied with a three-way servo-controlled spool valve connected to sources of positive and negative pressure. A computer-based system detects respiratory flow and computes the controlling signal for the valve by using a proportional-integral-derivative algorithm, to achieve desired patterns of flow and volume vs. time. The system was used with dogs and found to accurately induce various single-breath breathing patterns involving constant-flow inspirations and expirations as well as breath-hold periods. A similar system was used to induced repeated breaths with desired parameters for continuous exposure to particles and for ventilation of animals between experiments.

Aerosol deposition and dispersion characterize lung injury in a canine model of emphysema.

The deposition and dispersion of inhaled aerosol boluses were investigated as markers of lung injury in three dogs before and after emphysema was induced by papain exposure. After the experiments, lung damage was assessed histologically. Four unexposed dogs were used as controls. Effective air space diameter (EAD) was determined from aerosol deposition during a 5-s breath hold. Nonuniform ventilation was assessed from the spreading of the expired bolus, quantified as a coefficient of dispersion (CD), and from expired bolus skewness (SK). Experiments were done with a range of bolus penetrations and ventilatory flow rates. After papain exposure, EAD measured with the most penetrating boluses increased an average of 89% (P < 0.0001); CD and SK measured with boluses of medium penetration and a flow rate of 0.5 l/s increased an average of 24% (P < 0.02) and 98% (P < 0.002), respectively. The effects of lung injury on CD and SK increased with flow rate. Lung injury was confirmed by changes in lung mechanics and by histology. EAD measured with deeply penetrating boluses correlated significantly with the mean chord length measured morphometrically (P < 0.05). No correlation was found with more shallow boluses. The results indicate that EAD, CD, and SK are sensitive markers of lung injury in experimental emphysema and that EAD is a specific marker of increased air space size.

Exposure assessment for airborne man-made mineral fibres: the role of fibre dimensions.

Environmental exposures to man-made mineral fibres (MMMF) typically contain fibres which are polydisperse with respect to fibre dimensions. Fibre dimensions may influence their biological action through effects on: the efficiency of transport to target tissues; the residence time in target tissues; and the biological activity of fibres in contact with target cells. This variability of biological activity vs fibre dimensions should be accounted for when assessing exposure for epidemiological studies of the risk of cancer in subjects exposed to MMMF. In order to provide insight into the influence of fibre dimensions on the potential carcinogenicity of MMMF, this paper reviews literature concerning the sites of lung tumours, regional fibre deposition, biological effects of fibres in in vivo and in vitro systems, dissolution rates of fibres and rates of physiological clearance of inhaled particles. Tumorigenicity of fibres in contact with target tissue appears to be primarily a function of fibre length, whereas both fibre diameter and fibre length may affect the penetration of fibres through the respiratory tract as well as their residence time in target tissues. A methodology is presented to use this information to compute estimates of biologically effective exposure from the joint distribution of fibre lengths and diameters found in an environmental exposure.

Aerosol bolus dispersion and convective mixing in human and dog lungs and physical models.

The dispersion of aerosol boluses in the lung is a probe for convective mixing and has been proposed as a marker for abnormal lung function. To better understand the factors underlying this phenomenon, aerosol dispersion was compared in human subjects, dogs, and various physical models. In all systems, dispersion increased with the volumetric penetration of the aerosol bolus. The rate of this increase was 83% greater in humans compared with dogs. Dispersion in dogs was close to that in a packed bed with beads of 2.5 mm. Aerosol dispersion decreased with increasing flow rate in human subjects. An artificial larynx inserted into the straight tube caused a 33% increase in dispersion. In humans, aerosol dispersion was significantly correlated with forced expired flow between 25 and 75% of vital capacity. A 2-s pause between inspiration and expiration increased dispersion 23-58% in three isolated dog lungs but did not affect dispersion in the packed bed. The data suggest that lung geometry, flow rate, particle mobility, and the larynx all significantly affect aerosol dispersion by influencing the reversibility of aerosol transport between inspiration and expiration.

An abbreviated assessment of ocular exposure to ultraviolet radiation.

Individual behaviour has a very large effect on determining the exposure of the eye to solar radiation. To be able to examine the relationship between ocular exposure to ambient ultraviolet radiation and ocular disease, a model was developed previously that assessed cumulative ocular exposure from individual information on work and leisure activities. In this paper, we present a simplified version of the model that uses data on exposure during the middle of the day (9 a.m. to 3 p.m. solar time) during the northern 'summer' months (April to September). The ocular exposure determined by the simplified model is highly correlated with the full model (r = 0.98) and the simplified model predicts 62% of the total ocular exposure. This model should be useful for future epidemiologic studies of sun exposure and eye disease.

Assessment of papain-induced lung injury in isolated lungs by measurements of aerosol deposition and mixing.

Aerosol bolus inspirations were used to assess lung injury in 15 isolated dog lungs exposed to low (0-375 units) or high doses (600-1,200 units) of papain. Effective air space size (EAD) was determined from aerosol deposition during a 5-s breath hold. Convective mixing was assessed by the spreading of the expired bolus with respect to expired volume, quantified by a coefficient of dispersion (CD) equal to the square root of the difference in the variances of the expired and inspired boluses divided by the volumetric penetration of the bolus. After exposure, CD measured with deeply penetrating boluses increased by an average of 2.5% in the low-exposure group (P greater than 0.05) and 28.0% in the high-exposure group (P less than 0.0001). CD measured with shallowly penetrating boluses decreased by 4.3% (P less than 0.0001) in the low-exposure group and increased by an average of 18.3% in the high-exposure group (P less than 0.05). Papain exposure caused EAD to increase in some lungs and decrease in others. For deep bolus penetrations, EAD changed by an average of -0.8% in the low-exposure group (P greater than 0.05) and +21.1% in the high-exposure group (P greater than 0.05). Both EAD and CD appeared to be sensitive to lung injury. However, changes in EAD were less consistent than those in CD, possibly due to changes caused by lung injury in the regional distribution of inspired aerosol.

The long-term effects of visible light on the eye.

The relationship between exposure to sunlight and senile cataract, age-related macular degeneration, pterygium, and climatic droplet keratopathy was examined in 838 watermen who work on the Chesapeake Bay. The presence and severity of lenticular, corneal, and macular changes were assessed by either clinical examination or from stereo macular photographs. From detailed exposure histories, ocular exposure was estimated for three bands of visible radiation-violet (400 to 450 nm), blue (400 to 500 nm), or all visible (400 to 700 nm)-as well as for UV-A (320 to 340 nm) and UV-B (290 to 320 nm). The results with each band of visible radiation were similar. Neither cortical nor nuclear cataract was associated with ocular exposure to blue or all visible radiation, but pterygium and climatic droplet keratopathy were more common with higher exposures. Compared with age-matched controls, patients with advanced age-related macular degeneration (geographic atrophy or disciform scarring) had significantly higher exposure to blue or visible light over the preceding 20 years (odds ratio, 1.36 [1.00 to 1.85]) but were not different in respect to exposure to UV-A or UV-B. These data suggest that high levels of exposure to blue or visible light may cause ocular damage, especially later in life, and may be related to the development of age-related macular degeneration.

Ocular and facial skin exposure to ultraviolet radiation in sunlight: a personal exposure model with application to a worker population.

A model of ocular and facial skin exposure to UVB is presented that combines interview histories of work activities, leisure activities, eyeglass wearing, and hat use with field and laboratory measurements of UV radiant exposure. Site-specific exposure is expressed as the product of personal ambient exposure, defined as the ambient exposure while an individual is exposed to sunlight, and factors that describe the ratio of site-specific to personal ambient exposure. Ocular exposure is further corrected by the UV attenuation of typical eyewear. The model was used to compute cumulative and yearly exposures in a population of 838 watermen who work on the Chesapeake Bay and are highly exposed to sunlight. The model was found to be predictive of conditions known to be caused by excessive sun exposure--skin elastosis, climatic droplet keratopathy, and squamous cell carcinoma--and has been useful in several epidemiological studies.

Quantitative ultraviolet skin exposure in children during selected outdoor activities.

We determined the cumulative exposure of 3 body sites to ultraviolet radiation from sunlight for 126 children observed from 1-3 d during a variety of common recreational activities at a girl scout camp, baseball camp and community baseball field. Median arm exposure to children playing baseball at a camp ranged from 27.6% to 33.2% of the possible ambient exposure. These exposures are similar to adult exposures reported for comparable activities. Median exposure to the arm at the girl scout camp during mixed activities ranged from 9.0% to 26.5% of possible ambient exposure. At the girl scout camp, exposure both within and between activity groups varied substantially and were more variable than the baseball players' exposure. Arm exposure was greater than cheek and forehead exposure for all subject groups, with an arm-to-cheek exposure ratio ranging from 1.7 to 2.3. For organized sports, such as baseball, it may be possible to assign a single exposure estimate for use in epidemiologic studies or risk estimates. However, for less uniform outdoor activities, wide variability in exposure makes it more difficult to predict an individual's exposure.

Association of nonmelanoma skin cancer and actinic keratosis with cumulative solar ultraviolet exposure in Maryland watermen.

To establish the relationship between ultraviolet-B radiation and squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and actinic keratosis (AK), a cross-sectional prevalence survey was performed in a sample of 808 white, male watermen 30 years of age and older residing in the Eastern Shore of Maryland. A measure of personal cumulative ultraviolet-B exposure was determined for each subject from data collected through interviews and field and laboratory measurements. A personal interview elicited skin type, medication history, and other factors. Clinical diagnoses and histologic confirmation were done for current and previously removed skin tumors. The ratio of subjects with SCC to subjects with BCC was approximately 1:1; however, the ratio of BCC to SCC was 1.25:1 because BCC cases were more prone to multiple lesions. Watermen with SCC or AK but not BCC had higher average annual ultraviolet-B doses than age-matched controls. This was particularly marked in watermen younger than 60 years of age. Logistic regression showed that an older age, childhood freckling, and blue eyes significantly increased the risk of the development of all three types of skin tumor. Ease of sunburning was associated with BCC and AK, but not with SCC. Watermen in the upper quartile of cumulative ultraviolet-B exposure had a 2.5 times higher risk for the development of SCC when compared with the lower 3 quartiles. This suggests that high levels of ultraviolet-B exposure are important in SCC occurrence. The risk of AK developing was 1.5 times higher for those whose cumulative ultraviolet-B exposure exceeded the median. The relationship of BCC to cumulative ultraviolet-B exposure was not clear and this suggests that different etiologic mechanisms operate for SCC and BCC.

Ultraviolet exposure to children from sunlight: a study using personal dosimetry.

Childhood exposure to ultraviolet (UV) radiation in sunlight may be an important risk factor for later development of skin diseases. We quantified the UVB radiant exposure on the wrist and face of children performing mixed outdoor activities at a summer camp. Polysulfone film badges were attached directly to the skin for several hours and simultaneously were used to measure ambient UVB levels. The results for the ratio of site-specific exposure to ambient exposure indicate a high degree of intersubject variability, a parity of samples taken in right and left positions, and a significantly higher exposure on the wrist compared with the face. The technique was well accepted by the subjects but some badges could not be read because of loss or damage. Measurement of exposure ratios in additional settings as well as data on childhood activity patterns are needed for an overall assessment of childhood exposure.