W. G. Johanson

Multiple organ system failure and infection in adult respiratory distress syndrome.

Patients with the adult respiratory distress syndrome and multiple organ system failure have a high mortality rate despite extensive supportive therapy. We evaluated the role of multiple organ system failure and infection in 37 consecutive survivors of the syndrome, and 47 consecutive nonsurvivors on whom autopsies were done. Failure of the central nervous, coagulation, endocrine, gastrointestinal, and renal systems was common in all patients but was more frequent in those who died. Major infections occurred in 46 nonsurvivors and 22 survivors. All patients with bacteremia who had a clinically identified site of infection survived, whereas all patients with bacteremia without a clinically identified site of infection died. Autopsy results of the latter group showed infections requiring surgical drainage for complete therapy. Patients clinically septic but without bacteremia and without a clear site of infection were shown at autopsy to have pneumonia. Multiple organ system failure was more common in infected (93%) than noninfected (47%) patients. Vigorous evaluation and treatment of infection in patients with the adult respiratory distress syndrome may improve survival.

Role of salivary protease activity in adherence of gram-negative bacilli to mammalian buccal epithelial cells in vivo.

Serious illness is accompanied by markedly increased susceptibility to colonization of the respiratory tract by gram-negative bacilli and an increase in the number of such organisms which adhere to regional epithelial cells during incubation in vitro. Trypsinization of cells from normal subjects causes a similar increase in bacillary adherence. We studied bacillary adherence to buccal cells in vitro, protease activity of upper respiratory secretions with a fibrin plate technique, and the amount of fibronectin on the surface of buccal cells with a direct radioimmunobinding assay. Among 10 patients seriously ill with acute respiratory failure bacillary adherence to buccal cells and protease activity in secretions were increased compared with controls and cell-surface fibronectin was decreased; all patients were colonized in vivo with gram-negative bacilli. These changes were persistent and 80% of the patients died. Serial determinations were made in eight patients undergoing coronary artery bypass surgery. Following surgery, protease activity and bacillary adherence increased and cell-surface fibronectin decreased; 38% of coronary artery bypass patients became colonized. In these uncomplicated patients the changes observed were transient, largely returning to normal by the third postoperative day. Increased protease activity of secretions and alterations in epithelial cell surfaces as reflected by loss of buccal cell-surface fibronectin occur swiftly after major illness and appear to underlie enhanced cell adherence of bacilli and colonization of the upper respiratory tract. These findings suggest new approaches to the prevention of nosocomial pneumonia.

The Radiographic Resolution of Streptococcus pneumoniae Pneumonia

To determine the characteristics of the radiographic resolution of bacteremic Streptococcus pneumoniae pneumonia we examined serial chest roentgenograms in 72 patients. Consolidation disappeared in all patients by eight to 10 weeks; volume loss (9 per cent), plural disease (9 per cent), and stranding (19 per cent) often persisted beyond eight weeks. Resolution occurred earlier in patients less than 50 years old (P less than 0.05) and in the absence of alcoholism and underlying airways disease regardless of age (P less than 0.05). Delayed clearing occurred when these complicating factors were present in patients over 50. Lung cancer was not responsible for delayed resolution of pneumonia. We conclude that an appropriate interval for serial radiographic examinations after therapy for pneumococcal pneumonia is six weeks.

Aspiration pneumonia, anaerobic infections, and lung abscess.

Anaerobic pleuropulmonary infections are common in the setting of aspiration. Treatment is with penicillin or in mixed infections, penicillin and other appropriate antimicrobial agents. Four syndromes are commonly recognized. Simple pneumonitis resolves promptly with antibiotic therapy. If treatment is delayed, simple pneumonitis may evolve into a more fulminant process of necrotizing pneumonia with a significant mortality despite antibiotic therapy. Lung abscess, typically a subacute or chronic infection, responds well to antibiotic therapy so long as the cavity is drained via the communicating bronchus. Empyema requires surgical drainage by either closed or open thoracostomy if resolution is to be achieved.

The effect of almitrine bismesylate on hypoxemia in chronic obstructive pulmonary disease.

Almitrine bismesylate was studied for its effects on hypoxemia in 67 patients with chronic obstructive lung disease in a placebo-controlled, double-blind study. Arterial Po2 rose by 11.2 mm Hg (p less than 0.05) in 21 patients receiving 100 mg twice daily and by 6.0 mm Hg (p less than 0.05) in 22 patients receiving 50 mg twice daily. Arterial Pco2 decreased by 3.8 mm Hg (p less than 0.05) in the group receiving 100 mg twice daily but was unchanged in patients receiving 50 mg twice daily. Lung function was unaltered except for a slight increase in forced mid-expiratory flow in both dosage groups (p less than 0.05). The major side effect was the unexplained worsening of dyspnea, which occurred in 4 patients (19%) receiving 100 mg twice daily, 2 (9%) receiving 50 mg twice daily group, and 1 (4%) receiving placebo. Almitrine bismesylate improves arterial blood gas values in patients with chronic obstructive lung disease, apparently by reducing intrapulmonary ventilation-perfusion mismatching, and appears to be useful in the long-term management of these patients.

Pneumoconiosis Among Activated-Carbon Workers

The prevalence of respiratory symptoms and chest radiographic and spirometric abnormalities was assessed among 397 employees of an activated carbon plant. Definite radiographic findings of pneumoconiosis, consisting of p-type, rounded opacities in the lower lung fields without firbosis or coalescence, were present in 9.6% of men and were related to cumulative dust exposure. Lesser degrees of radiographic abnormality suggesting pneumoconiosis were present in 11% of men and 2% of women. Spirometric values were substantially lower in blacks than in whites. However, cumulative dust exposure was not an important determinant of pulmonary function in either race. Review of lung biopsy speciments that had been obtained previously in two employees revealed extensive carbon depositiion but minimal associated fibrosis. Prolonged inhalation of activated carbon dust leads to pulmonary deposition of carbon and raciographic signs of pneumoconiosis; such deposition has little, if any, effect on respiratory symptoms or pulmonary function.

Pulmonary Fibrosis with Small-Airway Disease: A Model in Nonhuman Primates

Bleomycin was administered intrabronchially to four baboons in doses of 1 mg/kg for four consecutive weeks. At necropsy 6 months later, the lesions produced differed markedly from those resulting from parenteral administration of bleomycin and consisted of diffuse foci of inflammation and fibrosis of the lung parenchyma associated with small airway lesions. Airway lesions were found in respiratory bronchioles and consisted of bronchiolar wall inflammation, hyperplasia of smooth muscles, and epithelia bronchiolization of adjacent alveolated structures. Many bronchioles were obliterated by the fibrotic process. Biochemical measurements confirmed the histologic appearance of increased lung collagen in three of four animals. These findings indicate that obstruction of small airways by processes which cause lung fibrosis may be separable physiologically from processes which affect only the lung parenchyma.

The effect of intraalveolar fluid on lung bacterial clearance

Appropriate animal models of lung bacterial clearance are difficult to establish in part because our current understanding of the pathogenesis of human pneumonia is imprecise. If all available models produced similar data their relevance to human infection would be strengthened. To assess consistency between two such models, we studied the effects of pulmonary edema and intratracheally injected protein on the pulmonary clearance of either aerosolized or intratracheally injectedStaphylococcus aureus orStreptococcus pneumoniae. Intraalveolar fluid, whether produced by increasing pulmonary capillary permeability or by intratracheal inoculation of bacteria, impaired lung bacterial clearance. This impairment varied with the organism employed. Proteinaceous intraalveolar fluid does not impair clearance by supporting bacterial multiplication and may enhance clearance of some organisms. Our results suggest that animal models of human lung infection are not easily constructed, remain problematic, and, at best, are only valid for the specific conditions of the model.

Elastase activity in bronchoalveolar lavage fluid from oxygen-exposed, Pseudomonas-infected baboons

The adult respiratory distress syndrome is a major cause of morbidity and mortality in critical care patients. Lung injury in this syndrome is frequently associated with lung infection. The combined insults result in an influx of neutrophils and damage to the pulmonary epithelium. We investigated whether active neutrophil elastolytic activity was present in the bronchoalveolar fluid in baboons with mild or moderate hyperoxic lung injury and infection. Group A (N=7) was exposed for 6 days to FIO2=0.8 and then inoculated by intratracheal bolus withPseudomonas aeruginosa strain DGI-R130 (PA); the FIO2 was reduced to 0.5. Group B (N=6) was exposed to similar concentrations of inspired oxygen but inoculated with buffered saline. Antibiotics included parenteral penicillin and topical gentamicin and polymyxin B. All 3 were given continuously in group B but stopped 24 h prior to PA inoculation in group A. Bronchoalveolar lavage fluid was collected 1 week before oxygen administration, when the FIO2 was reduced (day 6 or 7) and prior to necropsy (day 11). Hemodynamic, pulmonary function, microbiological, and biochemical variables were studied. Injured, infected animals (group A) had significant elevations of mean pulmonary artery pressure and decreases in total lung capacity and PaO2 compared both to baseline and to group B at day 11. At autopsy, group A had significant increases of bronchoalveolar lavage fluid (BALF) neutrophils and bacterial pathogens. Elastase levels in BALF (equal to 0 at baseline) rose to 136±98 ng/ml in group A vs. 6±14 ng/ml in group B. The elastase was inhibited by inhibitors of serine proteases including ones specific for neutrophil elastase. On Sephacryl S-300 chromatography the elastase activity eluted near humanα2-macroglobulin and separated from other proteolytic activity. These studies demonstrate a significant level of elastase in BALF from injured, infected baboons compared to injured, uninfected animals.

Acute effects of oleic acid-induced lung injury in baboons

Oleic acid induces lung injury in the baboon. Within 90 min of intravenous oleic acid injection, there are significant increases relative to baseline in the bronchoalveolar lavage fluid (BALF) contents of total protein, lactic dehydrogenase, hexosaminidase, acid protease, and angiotensin-converting enzyme, indicating increased alveolar permeability. When BALF is chromatographed on Sephadex G-200, the elution profiles of hexosaminidase, acid protease, and angiotensin-converting enzyme in BALF are similar to those from normal plasma. SDS-polyacrylamide gel electrophoresis of BALF proteins indicates a similar molecular weight distribution in baseline and post-oleic-acid BALF. No evidence of serine proteases active in the inflammatory process, and present in many cases of human adult respiratory failure, is found either by incubating BALF with hemoglobin and elastin substrates or by labeling BALF with3H-diisopropylfluorophosphate. However, there is a significant increase in α1-antiprotease activity in BALF relative to the baseline value. The activities in plasma of several acute phase reactants including antiproteases, fibronectin, and angiotensin-converting enzyme do not change in this acute phase of the lung injury. The data indicate that many biochemical markers used to indicate acute respiratory failure in humans do not change acutely in the expected fashion in this animal model of the disease.