Inflammatory cell distribution within and along asthmatic airways.

Asthmatic airways are infiltrated with inflammatory cells that release mediators and cytokines into the microenvironment. In this study, we evaluated the distribution of CD45-positive leukocytes and eosinophils in lung tissue from five patients who died with severe asthma compared with five patients with cystic fibrosis. For morphometric analysis, the airway wall was partitioned into an "inner" area (between basement membrane and smooth muscle) and an "outer" area (between smooth muscle and alveolar attachments). Large airways (with a perimeter greater than 3.0 mm) from patients with asthma or cystic fibrosis had a greater density of CD45-positive cells (p < 0.05) and eosinophils (p < 0.001) in the inner airway region compared with the same airway region in small airways. Furthermore, in small airways, asthmatic lungs showed a greater density of CD45-positive cells (p < 0.01) and eosinophils (p < 0.01) in the outer compared with the inner airway wall region. These observations indicate that there are regional variations in inflammatory cell distribution within the airway wall in patients with asthma that are not observed in airways from patients with cystic fibrosis. We speculate that this inflammatory cell density in peripheral airways in severe asthma may relate to the peripheral airway obstruction characteristic of this condition.

Recent trends in diagnosis and treatment of Clostridium difficile in a tertiary care facility.

BACKGROUND: With the prevalence of antibiotic use, the diagnosis and management of Clostridium difficile disease requires assessment. METHODS: In a retrospective review, patients with a positive culture, toxin, or both during 1 year were identified. Recent literature was reviewed. Results of culture and toxin, prior antibiotic use, antibiotic treatment history and cost were analyzed. RESULTS: Of 592 patients tested, 101 were positive; 96 of 101 were available for review. Of those positive tested for both, 45% were positive for toxin and culture. Sixty-two of 96 were treated with antibiotics; metronidazole was used in 90%. Ten of 62 antibiotic treatments were changed (mean 3 days). Ten days of metronidazole is 1/200th the cost of vancomycin. CONCLUSIONS: In 55% of the positive cases in which culture and toxin were obtained, one test was negative. As metronidazole's efficacy and cost compares favorably with vancomycin, metronidazole is the drug of choice. Any changes made to antibiotic regimens occurred prior to the 6 days recommended in the literature.

Phagocytosis of small carbon particles (PM10) by alveolar macrophages stimulates the release of polymorphonuclear leukocytes from bone marrow.

Recent studies have shown that an increased concentration of ambient particulate matter (PM10) is related to decreased pulmonary function and respiratory and cardiovascular mortality. The mechanisms responsible for this excess mortality are unknown and the relationship between the level of PM10 and the circulating leukocyte counts has not been previously investigated. We postulated that the deposition of PM10 in the peripheral lung stimulates alveolar macrophages (AM), which results in polymorphonuclear leukocyte (PMN) release from bone marrow (BM). To test this hypothesis, either colloidal carbon (CC) (n = 3) or saline (n = 4) was instilled into the lungs of rabbits and PMN release from BM was evaluated by using 5'-bromo-2'-deoxyuridine (BrdU). CC instillation in the lung shortened the transit time of PMN through the BM to 71.0 +/- 6.9 h compared with the saline controls (85.5 +/- 2.8 h, p < 0.01). The role of AM in this response was further investigated by incubating isolated AM in tissue culture medium either with or without the presence of CC, and measuring the effect of the supernatants on the release of PMN from the BM. The supernatant of AM incubated with CC shortened the PMN transit time through the BM to 74.9 +/- 3.7 h (p < 0.05) compared with the supernatant from the unstimulated AM (98.6 +/- 1.9 h) and medium alone (94.3 +/- 3.7 h). We conclude that the phagocytosis of CC by AM releases mediators (cytokines) that stimulate the BM to release PMN. We speculate that these newly released PMN may play an important role in the decline in lung function and high mortality seen in populations exposed to high concentrations of atmospheric PM10.

The effect of cigarette smoking on the bone marrow.

Chronic cigarette smoking produces a 20 to 25% increase in the number of peripheral blood leukocytes, and there is increasing evidence that these leukocytes are activated in the lung by the inhalation of cigarette smoke. The present study was designed to measure the effect of cigarette smoke inhalation on the rate of production and release of polymorphonuclear leukocytes (PMN) from the bone marrow into the peripheral blood. The thymidine analogue 5'-bromo-2'-deoxyuridine (BrdU) was used to pulse-label the dividing cells in the marrow of rabbits, measure their appearance in the peripheral blood, and calculate the time that PMN spend in the mitotic and postmitotic pools of the bone marrow. Comparison of animals exposed to 2 wk of cigarette smoke (n = 8) with sham-exposed controls (n = 9) showed that smoking decreased the mean transit time of PMNBrdU through the bone marrow from 97.3 +/- 3.0 h to 89.6 +/- 5.8 h (p < 0.001) by reducing the transit time of PMN in the postmitotic pool from 66.7 +/- 3.9 h to 53.7 +/- 0.7 h (p < 0.001). Both the mitotic (p < 0.05) and postmitotic (p < 0.05) pools of PMN increased in size following cigarette-smoke exposure. We conclude that chronic cigarette smoking stimulates the bone marrow, increases the size of the mitotic and postmitotic pools of PMN, and reduces the time PMN spend in the postmitotic pool in the marrow. These changes may contribute to the leukocytosis seen in cigarette smokers.

Localization of leukaemia inhibitory factor to airway epithelium and its amplification of contractile responses to tachykinins.

1. In neural tissue, leukaemia inhibitory factor (LIF) is an important trophic cytokine. In this investigation, we determined if LIF was present in human and guinea-pig airways and examined the role of this cytokine in modulating airway responses to endogenous and exogenous tachykinins as well as muscarinic receptor and beta-adrenoceptor stimulation. 2. The presence of LIF in both human and guinea-pig airways was determined by immunohistochemistry. Guinea-pig tracheal explants were incubated in CRML-1066 media containing LIF (0.5, 5 or 50 ng ml-1) for periods of 3, 6, 24 and 48 h. Tracheal rings were then transferred to organ baths for measurement of isometric force in response to carbachol, capsaicin, the neurokinin1 (NK1) receptor agonist [Sar9,Met(O2)11]-substance P (SP), the NK2 receptor agonist neurokinin A (NKA) and isoprenaline. 3. LIF immunoreactivity was observed primarily in basally situated cells in the airway epithelium of both large and small airways. Less intense immunoreactivity was observed in vascular endothelium and glandular epithelium. 4. Treatment with LIF (0.5 ng ml-1) for 3 and 6 h significantly increased contractile responses to capsaicin by 42% and 43%, respectively, compared to time controls, whereas higher concentrations of LIF (5 and 50 ng ml-1) enhanced capsaicin-induced contractions only after 6 h. After 24 h, responses to capsaicin were not significantly different from 0 h control. Contractile responses to capsaicin following exposure to LIF at any concentration for 24 h were not significantly different from relative time control values. 5. Responses to [Sar9,Met(O2)11]-SP, carbachol and isoprenaline were not influenced by time in culture or by exposure to LIF for up to 48 h. Contractile responses induced by NKA were not influenced by 3 or 6 h exposure to LIF, but at 24 and 48 h the mean maximum contractile responses to NKA were significantly increased by 33% and 35%, respectively, compared to control. 6. These results demonstrate that LIF is present in guinea-pig and human airway epithelium, and modulates airway responses to tachykinins. In the acute setting LIF augments the capsaicin-induced release of endogenous tachykinins, whilst in the longer term (> 24 h), LIF increases airway smooth muscle responses to tachykinins via an NK2 receptor selective mechanism. We conclude that LIF may be an important effector molecule in the response of airways to injury or inflammation.

The functional consequences of airway remodeling in asthma.

Structural changes in the airway walls involving extracellular matrix remodelling are prominent features of asthma. These changes are probably driven by mediators released as a consequence of chronic allergic inflammation. It is clear that changes in the extracellular matrix have the capacity to influence airway function in asthma. However, it is not clear how each of the many changes that occur in the airway wall contribute to altered airway function in asthma. Collagen deposition in the subepithelial matrix, and hyaluronan and versican deposition around and internal to the smooth muscle would be expected to oppose the effect of smooth muscle contraction. Conversely, geometric considerations would result in exaggerated airway narrowing for a given degree of smooth muscle shortening, as the airway wall is thickened by the deposition of these molecules internal to the smooth muscle. Elastin and cartilage reorganization and degradation in the airway walls would be expected to result in decreased airway wall stiffness and increased airway narrowing for a given amount of force generated by the smooth muscle. Degradation of matrix associated with the smooth muscle may both decrease the stiffness of the parallel elastic component and uncouple smooth muscle from the load provided by lung recoil, allowing exaggerated smooth muscle shortening. Increase in muscle mass may be associated with an increase, a decrease or no change in smooth muscle contractility. If an increase in muscle mass was associated with preservation of its contractile capacity modelling studies suggest that it could be the most important contributor to exaggerated airway narrowing. Modelling studies also suggest that the pattern of mucosal folding during smooth muscle contraction may be an important determinant of airway narrowing. The greater the number of folds, and the stiffer the subepithelial collagenous layer the more resistant the airway will be to narrowing.

Morphologic determinants of airway responsiveness in chronic smokers.

Nonspecific bronchial hyperresponsiveness (NSBH) occurs in asthmatics and in smokers who have airway obstruction. NSBH may be caused by different mechanisms in these conditions. We hypothesized that NSBH in smokers was a consequence of the structural changes that occur in chronic obstructive pulmonary disease (COPD) and lead to airway obstruction. We measured nonspecific bronchial responsiveness, assessed by PC20, in 77 smokers who had mild to moderate airflow obstruction prior to lung resection for a pulmonary nodule. We related airway responsiveness to baseline airway function (FEV1 % predicted), to functional (PLmax, PL90, and P-V curve shape) and morphometric (alveolar attachments) markers of lung elasticity as well as to thickening in small airways. Airway wall thickness, internal and external to the outer border of smooth muscle was quantified by plotting the square root of airway wall area versus a marker of airway size, airway internal perimeter (Pi). PC20 was significantly related to FEV1% predicted and PLmax. and when these functional parameters were controlled for, PC20 was also inversely related to airway wall thickness. There was also a trend for the most responsive patients to have fewer alveolar attachments per millimeter on the external perimeter of the airway walls. These data suggest that exaggerated nonspecific airway narrowing in COPD is secondary to structural changes caused by the disease.

Polymorphonuclear leukocyte transit times in bone marrow during streptococcal pneumonia.

The release of polymorphonuclear leukocytes (PMN) from the bone marrow (BM) is a hallmark of acute inflammatory conditions. BM stimulation may increase the toxic potential of these newly released PMN and influence their behavior at inflammatory sites. The present study was designed to measure the transit time of PMN in the mitotic and postmitotic pools of the BM in rabbit using 5'-bromo-2'-deoxyuridine (BrdU). Blood samples were obtained at 2- to 24-h intervals from 24 to 192 h after a single BrdU injection, and BrdU-positive PMN (PMNBrdU) was detected as they appear in the circulating blood, using immunohistochemistry. The intensity of nuclear staining for BrdU was used to define a single generation of PMN and graded as either weakly (G1), moderately (G2), or highly (G3) stained. The mean +/- SE transit time of PMNBrdU through the BM was 95.6 +/- 3.6 h, with 51.1 +/- 5.9 h in the mitotic and 65.4 +/- 5.4 h in the postmitotic pool. Streptococcus pneumoniae instillation in the lung (n = 3) shortened the transit time of PMN through the BM to 54.0 +/- 2.6 h with a shorter time in both the mitotic (36.2 +/- 5.7 h) and the postmitotic pool 34.6 +/- 0.8 h). All these values were shorter than the control values (P < 0.05). We conclude that Streptococcus pneumoniae shortens the transit time of PMN in the mitotic and postmitotic pools in the marrow, which may result in the release of immature PMN with higher levels of lysosomal enzymes into the circulation.

Density dependence of pulmonary resistance: correlation with small airway pathology.

The density dependence of maximal expiratory flow is not an effective test of the site of airway narrowing in obstructive lung disease. We hypothesized that the density dependence of pulmonary resistance (DD,RL) would be more closely related to the degree of airway narrowing and peripheral airway pathology in smokers. We measured maximal expiratory flow at 50% vital capacity (V'max50) and lung resistance (RL) breathing air and 80% helium-20% oxygen, and calculated density dependence of V'max50 and RL in 40 patients who had moderate airflow obstruction and in 10 normal subjects. We compared the density dependence of RL and V'max50 with the degree of airway obstruction and bronchiolar pathology scores in 27 patients with resected lung specimens. There were no differences in DD of V'max50 or RL between normal subjects and patients, and no relationship between the degree of obstruction or the bronchiolar pathology score and the DD of these measurements. There were significant relationships between V'max50, RL and the bronchiolar pathology scores. In conclusion, lung resistance and maximal expiratory flow are related to the severity of peripheral airway pathology, but there is no relationship between the severity of obstruction or the severity of peripheral airway pathology and the density dependence of maximal expiratory flow or lung resistance.

Erythrocyte and polymorphonuclear cell transit time and concentration in human pulmonary capillaries.

Pulmonary capillary transit times were examined in patients who required lung resection by use of 99mTc-labeled macroaggregates (99Tc-MAA) and chromium-labeled erythrocytes (51Cr-RBC) to measure regional blood flow and volume in the resected lung. Cell flow (cells.ml-1.s-1) to each resected lung sample was determined by multiplying the number of polymorphonuclear leukocytes (PMN) per milliliter of circulating blood by the blood flow to that sample. Capillary blood volume was obtained by multiplying the morphometrically determined fraction of pulmonary blood in capillaries by the total 51Cr-RBC volume in each sample. Cell concentrations (cells/ml) in capillary blood were calculated morphometrically, and capillary transit times were obtained by dividing cell concentration by cell flow. The results show that PMN transit times were 60-100 times longer than the RBC transit times, with a 22% overlap between their distributions. We conclude that PMN are concentrated with respect to RBC in pulmonary capillary blood because of differences in their transit times and that these long transit times provide an opportunity for PMN-endothelial interactions.

Regional and fibre type glycogen utilization patterns in the hamster diaphragm following swimming.

The purpose of this study was to determine the regional and myofibrillar ATPase (M-ATPase) fibre type glycogen utilization patterns in response to increased ventilation induced by pre-exhaustive (Pre-Exh) and exhaustive (Exh) durations of swimming. Twenty-eight hamsters were studied: six controls (Con), 11 Pre-Exh (swam 82 min), 11 Exh (swam to exhaustion). We examined the optical density of PAS-stained fibres from the different regions of the diaphragm as a measure of glycogen remaining after the exercise or control period. The optical densities of PAS-stained fibres in most M-ATPase fibre types and diaphragmatic regions for the Pre-Exh and Exh groups was less than those in the Con hamsters except for the optical densities of all the M-ATPase fibre types in the sternal region. The optical densities of PAS-stained fibres in different regions and M-ATPase fibre types did not differ in the Exh and Pre-Exh groups. This data indicates that significant glycogen utilization occurred in all three M-ATPase fibre types in the costal, and both the thoracic and abdominal surface of the crural diaphragm in hamsters following pre-exhaustive and exhaustive durations of swimming. Glycogen utilization was greater in type 1 fibres of the thoracic surface of the crural region than in the type 1 fibres of the sternal region of the Pre-Exh group. Further, significant utilization of glycogen did not occur in any of the three M-ATPase fibre types of the sternal region of the diaphragm following prolonged durations of swimming. It would appear that glycogen is an important substrate in the hamster diaphragm during swimming.(ABSTRACT TRUNCATED AT 250 WORDS)

Lung structure and function in cigarette smokers.

BACKGROUND: Cigarette smoking produces an inflammatory response in the airways of everyone but only 15-20% of smokers develop airways obstruction. The present study concerns the relative importance of peripheral airways inflammation and the emphysematous destruction of the parenchymal support of the airways in the pathogenesis of this obstruction. METHODS: A total of 407 patients with a diagnosis of lung tumour performed pulmonary function tests a day or two before a lung or lobar resection. The specimens were fixed in inflation and analysed at the gross and microscopic level to determine the extent and severity of the emphysematous process, the number of alveoli supporting the outer walls of the airways, and the average distance between alveolar walls. The severity of the inflammatory process in the respiratory and nonrespiratory bronchioles was also assessed using a previously established grading system. RESULTS: The lung function test showed that a decline in FEV1 was associated with an increase in residual volume and a decrease in the diffusing capacity for carbon monoxide and a reduction in the lung maximum elastic recoil pressure. The prevalence of grossly visible emphysema increased as FEV1 declined, but the extent and severity of these lesions and the number of alveoli supporting the outer walls of the peripheral airways was similar at all levels of FEV1. The system used to grade inflammatory response in the peripheral airways failed to identify a specific defect responsible for the physiological abnormalities. CONCLUSION: The reduction in FEV1 associated with chronic cigarette smoking can be partially explained by loss of lung elastic recoil pressure which reduces the force driving air out of the lung. This loss of elastic recoil pressure is attributed to microscopic enlargement of the air spaces rather than to grossly visible emphysema. The exact nature of the lesions responsible for the peripheral airways obstruction remains to be identified.

Appropriate interpretation of indirect calorimetry for determining energy expenditure of patients in intensive care units.

Energy expenditure varies with patient agitation. We asked whether energy expenditure determined from 5 minutes of measurement with less than 5% variation in minute-to-minute measurements (short mean) was similar to energy expenditure determined from a longer measurement period (long mean; average duration: 31 minutes). The difference between the short mean and the long mean was less than 5% for 42 of 47 patients in intensive care units; the difference was more than 10% for 2 patients. We also generated a statistical model simulating energy expenditure measurement variations of 5% to 20%, and calculated the necessary measurement durations required to achieve a 3% error in measurement. The statistical model showed that for energy expenditure variations of 5%, 10%, 15%, and 20%, the necessary durations of measurement to achieve a 3% error were 3, 9, 16, and 25 minutes, respectively. We conclude that energy expenditure may be determined using the mean of a 5-minute period of measurement if variation in that measurement is less than 5%. Larger variation requires longer periods of measurement.

Pulmonary vascular abnormalities and ventilation-perfusion relationships in mild chronic obstructive pulmonary disease.

Morphologic changes in pulmonary muscular arteries may modify the mechanisms that regulate the pulmonary vascular tone and contribute to maintaining an adequate ventilation-perfusion (VA/Q) matching in patients with chronic obstructive pulmonary disease (COPD). To analyze the relationships between the abnormalities of pulmonary muscular arteries and the degree of VA/Q inequality, and to assess the effect of these abnormalities on the changes in VA/Q relationships induced by oxygen breathing, we studied a group of patients with mild COPD undergoing resective lung surgery. According to the degree of airflow obstruction and the increase in VA/Q mismatch produced by 100% O2 breathing (delta logSD Q), patients were divided into three groups: (A) patients with normal lung function, (B) patients with airflow obstruction and a high response to oxygen (delta logSD Q > 0.4), and (C) patients with airflow obstruction and a low response to oxygen (delta logSD Q < 0.4). Pulmonary arteries in Groups B and C showed narrower lumens and thicker walls than in Group A. These morphologic changes were produced mainly by an enlargement of the intimal layer and were more pronounced in Group C than in Group B. The assessment of intimal area as a function of artery diameter showed that the increase in intima in Group C took place predominantly in arteries with small diameters (< 500 microns). The mean intimal area on each subject correlated with both the PaO2 value (r = -0.46, p < 0.05) and the overall index of VA/Q mismatching (r = 0.51, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Static bone histomorphometry in preterm and term babies.

The nature and pathophysiology of the bone loss which occurs in term and especially preterm neonates are poorly understood, and it is unclear whether this neonatal osteopenia results from impaired bone formation or increased bone resorption. This study compared the static bone histomorphometry of preterm and term babies, employing iliac crest bone biopsy specimens obtained postmortem. All the babies died within the first 6 days of life and none had any clinical, biochemical or radiologic evidence of metabolic bone disease. The trabecular bone volume, as well as static parameters of bone formation (OV/TV, OV/BV, OS/BS, OB.S/BS) did not differ significantly in preterm and term babies. Although time-spaced tetracycline labelling could not be employed in the present study, evidence of rickets was not apparent. Parameters of bone resorption in preterm babies were, however, significantly higher (p = 0.01) than those of term babies, suggesting that increased bone resorption and not impaired formation, underlies the development of osteopenia in the preterm neonate.

Circadian rhythm of glycogen in the hamster diaphragm.

The purpose of this study was to determine the diurnal fluctuation of glycogen stores for the whole hemidiaphragm and within a specific myofibrillar ATPase (M-ATPase) fibre type and diaphragmatic region. Fifty-six golden Syrian hamsters were randomly divided into six groups according to the time of sampling biopsies from the diaphragm: 03:00, 07:00, 11:00, 15:00, 19:00, and 23:00. The right hemidiaphragm was quick frozen and biochemically assayed for glycogen levels. Biopsies from the left hemidiaphragm of the same animal were cut from the anterior costal and crural regions, and stained with periodic acid--Schiff (PAS) and for M-ATPase. Optical density measures of PAS-stained fibres were determined to quantitate glycogen in different M-ATPase fibre types and diaphragmatic regions. Biochemical assay of the entire hemidiaphragm showed slightly greater glycogen content of biopsies taken at 11:00 and 15:00 than at 03:00, 19:00, and 23:00 (range of differences: 6.4-10.0%). However, glycogen levels within a specific M-ATPase fibre type and diaphragm region were not different in biopsies sampled at different times. Because the hamster has a small diurnal variation of glycogen in the diaphragm, which is similar to the small diurnal variation of glycogen in human skeletal muscle, this species may be a good animal model for metabolic studies of the diaphragm that could be affected by diurnal glycogen variability.

Small airways dimensions in asthma and in chronic obstructive pulmonary disease.

The purpose of this study was to compare the dimensions of the peripheral airways in fatal asthma with those from patients with nonfatal asthma, mild COPD, and normal lung function. Lung specimens from eight individuals who had fatal asthmatic attacks were obtained at postmortem and compared with similar specimens from three asthmatic patients who died of an unrelated cause and four specimens obtained from known asthmatic patients who required lung resection for tumor. These 15 asthmatic lungs were also compared with lungs resected for peripheral neoplasms from 15 patients with normal airway function (FEV1, % of predicted > 85) and 15 patients with mild chronic airflow obstruction (FEV1, % of predicted < 85). All membranous airways with a long-short diameter ratio of 3:1 or less were examined. The smooth muscle and the tissue areas external and internal to the muscle layer were traced using a Bioquant BQ System 4. The same system was used to evaluate the fraction of the submucosa and adventitia taken up by blood vessels. The adventitial, submucosal, and muscle area of the asthmatic airways were greater than those of COPD and control (p < 0.01), and the muscle area was greater in COPD than in control lungs (p < 0.05). These parameters were also greater in the 8 patients with fatal asthma compared with the 7 patients with nonfatal asthma (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of positive end-expiratory pressure on leukocyte transit in rabbit lungs.

Previous experiments in humans and animals have shown that neutrophils (PMN) are delayed in the lung by the inhalation of cigarette smoke. Others have shown that cigarette smoking raises airway resistance, and it follows that this will increase the expiratory time constant of the airways. When the expiratory time constant of the airways exceeds that of the chest wall, alveolar pressure will rise and compress alveolar capillaries. To determine the effect of alveolar compression on PMN retention, we measured the arteriovenous (A-V) difference for leukocytes across the lung and determined the retention of 51Cr-labeled PMN in the lungs of anesthetized ventilated rabbits. The results show that the application of positive end-expiratory airway pressure (PEEP) produced an immediate difference for PMN across the lung, which disappeared in approximately 3 min when PEEP was continuously applied. This effect was attributed to alveolar compression rather than reduced cardiac output, because a similar A-V difference for PMN was observed in separate experiments in which cardiac output was maintained by vascular expansion during PEEP. The results also show that, when PEEP was continuously applied for approximately 30 min, it failed to increase the percent retention of either inactivated (PEEP = 14 +/- 2% vs. non-PEEP 16 +/- 3%) or activated (PEEP = 62 +/- 7% vs. non-PEEP 63 +/- 6%) 51Cr-PMN. We conclude that the application of PEEP traps PMN in compressed alveolar capillaries, creating an immediate A-V difference that disappears as blood flow is redistributed to vessels that are not compressed by PEEP.(ABSTRACT TRUNCATED AT 250 WORDS)

Fiber type and regional differences in oxidative capacity and glycogen content in the hamster diaphragm.

The purpose of this study was to define variability of the oxidative capacity and glycogen content between different fiber types and regions of the hamster diaphragm. Using histochemical and microphotometric techniques, the oxidative capacity (identified by nicotinamide-adenine dinucleotide tetrazolium reductase reaction end product) and glycogen levels (identified by the periodic acid-Schiff stain test) were examined in three myofibrillar ATPase (M-ATPase) fiber types and four diaphragmatic regions: sternal, anterior costal, thoracic surface of the crural (thor/crur), and abdominal surface of the crural (abd/crur). Most regional differences were found between the crus and the rest of the diaphragm. There were no differences in the oxidative capacity between diaphragmatic regions in the types 1 and 2a fibers, but the type 2b fibers in the thor/crur region had the greatest oxidative capacity and the 2b fiber in the sternal region had the lowest oxidative capacity. There were differences in glycogen content between diaphragmatic regions for all of the three M-ATPase fiber types. Variability in oxidative capacity between fiber types was demonstrated in all regions except the thor/crur region. Variation in glycogen content between fiber types was only demonstrated in the two surfaces of the crus. The type 2b fiber demonstrated the most differences from types 1 and 2a fibers in oxidative capacity and glycogen content in the different diaphragmatic regions, whereas the types 1 and 2a fibers demonstrated few differences from each other in these features across the different diaphragmatic regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Mineral particles in the human bronchial mucosa and lung parenchyma. II. Cigarette smokers without emphysema.

The effects of cigarette smoke on the microanatomic deposition and retention pattern of exogenous mineral particles is unknown. To determine how cigarette smoke affects long-term particle retention in those with minimal smoke-related disease, we selected autopsy lungs from ten smokers without evidence of emphysema at autopsy, and used analytical electron microscopy to examine exogenous mineral particle concentration in the mucosa of seven different bronchi of varying sizes and four parenchymal sites fed by those bronchi. These data were compared with values from twelve lifetime nonsmokers. Overall, total mean particle burden in the parenchyma in the smokers and nonsmokers was similar, but there was a markedly decreased particle load retained in the smokers' airways. The consistent increase in particle burden seen in nonsmokers as airways became narrower and more distant from the carina was lost in many, but not all, of the smokers, especially for particles larger than 1 micron, and this effect did not appear to depend on amount of smoking. Rare polonium particles were found but were too sparse to use as a smoke distribution marker. However, calcium-containing particles, previously suggested by us to represent calcium carbonate actually derived from the smoke, were present in greatest concentration in the larger airways and distal parenchyma. These observations indicate the following in smokers without parenchymal smoke-induced structural damage: (1) Overall, cigarette smoking disrupts the normal retention (? deposition) pattern of particles in the airways. (2) Cigarette smoking leads to markedly decreased long-term retention of exogenous mineral particles in the airways without significantly affecting overall tissue particle retention. (3) The distribution of calcium particles in the airways and parenchyma in smokers is similar to that predicted in a recently published model of smoke particle deposition, and further supports the idea that calcium-containing particles can be used as a direct tracer of smoke particle deposition. In the present study this distribution indicates that the large airways and parenchyma receive the greatest smoke deposition. (4) Within the group of smokers, some people appear resistant to the disruptive effects of smoke on particle retention patterns, whereas other people smoking comparable amounts show markedly abnormal retention patterns. The latter may have unusual sensitivity to cigarette smoke and perhaps susceptibility to smoke-induced diseases.