Pyoderma gangrenosum in a thoracotomy wound associated with a pulmonary cavitating lesion.

We present a patient with both pyoderma gangrenosum in a thoracotomy wound and a pulmonary cavitating lesion with the histological features of Wegener's granulomatosis. An ulcer with blue undermined edges developed in our patient's thoracotomy scar after a lobectomy was carried out for the cavitating lung lesion and c Antineutrophil Cytoplasmic Antibodies (cANCA), which is highly specific for active Wegener's granulomatosis but was negative at the time of her skin lesion. This suggests that our patient had cutaneous pyoderma gangrenosum rather than cutaneous Wegener's granulomatosis, although the two conditions may occasionally have similar clinical and histological features.

Activated T-lymphocytes and eosinophils in the bronchial mucosa in isocyanate-induced asthma.

We have studied the phenotype and activation status of leukocytes in the bronchial mucosa in patients with isocyanate-induced asthma. Fiberoptic bronchial biopsy specimens were obtained from nine subjects with occupational (five toluene- and four methylene diisocyanate-sensitive) asthma, 10 subjects with extrinsic asthma, and 12 nonatopic healthy control subjects. Bronchial biopsy specimens were examined by immunohistology with a panel of monoclonal antibodies and the alkaline phosphatase-antialkaline phosphatase method. There was a significant increase in the number of CD25+ cells (interleukin-2 receptor-bearing cells, presumed "activated" T-lymphocytes; p less than 0.01) in isocyanate-induced asthma compared with that of control subjects. There were also significant increases in major basic protein (BMK-13)-positive (p less than 0.02) and EG2-positive (p less than 0.01) cells that represent total and "activated" eosinophil cationic protein-secreting eosinophils, respectively. In agreement with our previous findings, CD25+ (p less than 0.01), BMK-13 (p less than 0.03), and EG2+ (p less than 0.01) cells were also elevated in extrinsic asthma. No significant differences were observed in the numbers of T-lymphocyte phenotypic markers (CD3, CD4, and CD8) between subjects with asthma (isocyanate-induced and extrinsic) and control subjects. Similarly, no significant differences in immunostaining for neutrophil elastase (neutrophils) or CD68 (macrophages) were observed. The results suggest that isocyanate-induced occupational asthma and atopic (extrinsic) asthma have a similar pattern of inflammatory cell infiltrate. The results support the view that T-lymphocyte activation and eosinophil recruitment may be important in asthma of diverse etiology.

Application of monoclonal antibodies against major basic protein (BMK-13) and eosinophil cationic protein (EG1 and EG2) for quantifying eosinophils in bronchial biopsies from atopic asthma.

A monoclonal antibody prepared against the eosinophil major basis protein (MBP) was compared with the anti-eosinophil cationic protein (ECP) antibodies (EG1 and EG2) in immunostaining of bronchial biopsies from atopic asthma and controls. Anti-MBP (designated BMK-13) did not cross-react with other eosinophil basic proteins (i.e. ECP, eosinophil peroxidase [EPO] or eosinophil-derived neurotoxin [EDN]) and stained more than 98% of peripheral blood eosinophils irrespective of their degree of activation. EG2 stained 15% of resting and 75% of activated eosinophils; EG1 recognized 74% and 78% of resting and activated cells, respectively. The numbers of BMK-13, EG1 or EG2-positive staining cells in bronchial biopsies from asthma were significantly greater than atopic non-asthmatics (P less than 0.02, P less than 0.01 and P less than 0.05, respectively) and normal non-atopic controls (P less than 0.001). For each of the various groups studied, the rank order for the number of eosinophils stained was BMK-13 greater than EG1 greater than EG2. BMK-13 stained significantly more cells from bronchial biopsies of atopic asthma and atopic non asthma when compared to EG2 (P less than 0.001 and P less than 0.05, respectively). Since only a proportion of BMK-13+ cells were EG2+, these results suggest that not all tissue eosinophils are actively secreting. Thus, BMK-13 can serve as a useful pan-eosinophil marker in tissue sections since it appears to stain most eosinophils.

Eosinophils, T-lymphocytes, mast cells, neutrophils, and macrophages in bronchial biopsy specimens from atopic subjects with asthma: comparison with biopsy specimens from atopic subjects without asthma and normal control subjects and relationship to bronchial hyperresponsiveness.

Bronchial biopsy specimens were obtained by fiberoptic bronchoscopy from 21 atopic subjects with asthma, 10 atopic subjects without asthma, and 12 normal healthy control subjects. With immunohistochemical techniques and a panel of monoclonal antibodies, inflammatory cells were identified and counted in the bronchial mucosa. The mean number of leukocytes (CD45+) and T-lymphocytes (CD3+, CD4+, and CD8+) at two airway levels in the subjects with asthma tended to be higher than in the other groups, but this difference did not achieve statistical significance. Similarly, there were no significant differences in the numbers of mucosal-type or connective tissue-type mast cells, elastase-positive neutrophils, or Leu-M3+ cells in the airway mucosa of subjects with asthma compared with atopic subjects without asthma and healthy control subjects. In contrast, significantly more interleukin-2 receptor-positive (CD25+) cells and "activated" (EG2+) eosinophils (EOSs) were present in the airways of subjects with asthma at both proximal and subsegmental biopsy sites. When the relationships between numbers of T-lymphocytes, activated (CD25+) cells, and EOSs were analyzed, there were positive correlations between CD3 and EG2, between CD3 and CD25, and between CD25 and EG2 positive cells in the airways of subjects with asthma. Furthermore, the ratio of EG2+ to CD45+ cells correlated with the provocative concentration of methacholine that caused a 20% decrease of FEV1 in hyperresponsive subjects. Although these associations do not prove a causal relationship, the results support the hypothesis that activated (CD25) T-lymphocytes release products which regulate recruitment of EOSs into the airway wall. In addition, our findings suggest that, in the large airways at least, asthma is not associated with hyperplasia of either mucosal-type or connective tissue-type mast cell.

Physicians' management of health effects related to industrial exposures: two case reports.

Although physicians play a vital role in diagnosing and treating health effects related to industrial exposures, most physicians have limited training in occupational and environmental medicine. Two cases of industrial exposure, one affecting an individual and the other, a community, are described to illustrate the need for physicians' awareness of such exposure and their need to know how to manage potential health effects. Resources to assist in identifying and managing these exposures and their related conditions are discussed.

Influence of smoking on radiographic profusion and pleural changes in asbestos-exposed subjects.

The influence of smoking on pleural and parenchymal radiographic changes, particularly in asbestos-exposed cohorts, has been debated. We studied this issue in 440 asbestos-exposed subjects referred for evaluation between 1981 and 1985. Information was obtained on age, exposure, and smoking. Chest radiographs were independently read by three "B" readers under blind conditions and it was determined that 80.5% of the subjects had a history of smoking. The odds ratio for smoking and parenchymal opacities greater than or equal to 1/0 was 1.98 (95% confidence interval, 1.2 to 3.3); this association was not affected by adjustment for asbestos exposure and/or age. A dose-response pattern emerged between increasing pack-years and parenchymal opacities greater than or equal to 1/0; the effect between asbestos exposure and smoking appeared to be additive. No associations were found between smoking and pleural abnormalities. The findings in this investigation are consistent with prior studies showing an influence of smoking on radiographic parenchymal, but not pleural, changes, at least in asbestos-exposed groups. The anatomical equivalent of these radiographic changes and their impact, if any, on the natural history of asbestos-associated disease remains unclear.

Rehabilitation of patients with chronic respiratory disease.

The difficulties that face the patient with chronic respiratory disease are complex and interrelated. Caring for such patients requires a holistic approach, including psychologic support and education of patient and family, combined with physical therapy, administration of bronchodilators, and oxygen therapy.

Effect of methylprednisolone on experimental noncardiogenic pulmonary edema.

Methylprednisolone, 30 mg/kg body weight, was given to dogs 30 min and 4 h after injection of monocrotaline to produce noncardiogenic pulmonary edema. Control animals received monocrotaline but not corticosteroids. After 6 h the steroid-treated animals demonstrated significantly butter gas exchange and significantly less pulmonary edema. A possible mechanism of this beneficial effect of steroids is inhibition of complement-leukocyte interactions which may mediate pulmonary microvascular injury. The results lend some support to the clinical practice of short-term pharmacologic doses of steroids in noncardiogenic pulmonary edema.

Rapid, shallow ventilatory pattern during exercise after histamine, bronchopprovocation.

The ventilatory response to inhaled histamine sufficient to double specific airway resistance was studied at rest and with exercise in normal subjects. There were no ventilatory alterations at rest but during steady-state exercise the subjects adopted a rapid, shallow breathing pattern. Despite this change and increased resistance over-all ventilation and oxygen consumption were unchanged.

Effect of PEEP on lung water content in experimental noncardiogenic pulmonary edema.

After administration of monocrotaline to dogs to produce noncardiogenic pulmonary edema, one-half of the animals (controls) were treated with intermittent positive pressure breathing (IPPV), and one-half with that ventilation plus the addition of 10 cm H2O of positive end-expiratory pressure (PEEP). After 6 h, the animals treated with PEEP demonstrated significantly better arterial oxygenation and reduced AaDO2, but lung water, quantitated either postmortem or in vivo by indicator-dilution techniques, was no less than controls. Although PEEP improves gas exchange, it fails to modify the degree of pulmonary edema represent.

The effect on respiratory drive of a prolonged physical conditioning program.

Nine sedentary men 21 to 35 yr of age took part in a physical conditioning program involving regular aerobic exercise over a period of 6 to 8 wk. There was significant improvement in indexes of cardiorespiratory fitness. Ventilatory and mouth occlusion pressure responses to CO2 at rest and during threadmill exercise was measured before and after training. The slopes of the regression VE/PCO2 increased during exercise (p < 0.05), but not significantly at rest. The slopes of the regression of occlusion pressure at 100 ms versus PCO2, (P100/PCO2) did not change significantly at rest or during exercise. The VE/PCO2 and P100/PCO2 did not change from rest to exercise, and showed no relation to indexes of fitness. It is suggested that the low respiratory drive seen in some athletes is not due to the adaptation that results from short-term training. The possibility that long-term training may result in decreased responsiveness to CO2 cannot be excluded.

Low-density gas breathing during exercise in chronic obstructive lung disease.

Because breathing low-density helium-oxygen gas mixture has been reported as improving ventilatory mechanics in chronic obstructive pulmonary disease (COPD) patients and reducing the oxygen cost of ventilation in exercising normal subjects, it might prove useful in COPD physical conditioning programs. 7 COPD patients performed incremental exercise to tolerance while breathing either air on 79% helium-21% oxygen mixture. There was a tendency for low-density gas breathing to stimulate a higher ventilation at any given work load. As a result there was a tendency to greater tolerance with air breathing. Throughout exercise there was no statistically significant difference in endurance, oxygen consumption, heart rate, or ventilatory parameters suggesting that the helium-oxygen mixture was not beneficial to exercise performance.

Oxygen-assisted exercise in chronic obstructive lung disease. The effect on exercise capacity and arterial blood gas tensions.

Twenty-six patients with severe chronic obstructive lung disease exercised on a treadmill while breathing either room air, supplementary compressed air, or O2. Endurance was significantly increased by O2, but there was no improvement in maximal work rate. No relation was found between increased endurance and the degree of hypoxia, hypercarbia, or acidosis during exercise or the changes in these while breathing O2.