Unaffected Lung Research Articles

Experimental Vaccination of Pigs with an Actinobacillus pleuropneumoniae Serotype 5b Capsular Polysaccharide-Tetanus Toxoid Conjugate

The protective efficacy of an Actinobacillus pleuropneumoniae serotype 5b capsular polysaccharide-tetanus toxoid conjugate (Ap5bCP-TT) against homologous challenge of pigs was investigated. Four pigs were non-vaccinated controls (group A), 4 pigs were injected with adjuvant without antigen (group B) and 8 pigs were vaccinated with Ap5bCP-TT and adjuvant (group C). Pigs vaccinated with Ap5bCP-TT developed antibody responses to the capsular polysaccharide from A. pleuropneumoniae serotype 5b (Ap5bCP). After challenge, all pigs in groups A and B had severe clinical signs of disease and were euthanized. In group C, 3 out of 8 pigs showed severe symptoms and were euthanized. Five pigs in group C survived throughout the study. The post challenge observation period was 72 h. All pigs were subject to necropsy and results from gross pathological findings and microbiological examination are described. Pigs vaccinated with Ap5bCP-TT had statistically significant reduced values of the mass ratio of affected to unaffected lung tissue compared to pigs in groups A and B (p = 0.01 and p = 0.007, respectively). The results showed that Ap5bCP-TT-vaccination had considerable protective efficacy against lethality and pulmonary lesions caused by experimental infection with A. pleuropneumoniae serotype 5b.

Immunohistochemical distribution of surfactant apoprotein-A in congenital diaphragmatic hernia

The high mortality for congenital diaphragmatic hernia (CDH) has been attributed to a combination of pulmonary hypoplasia and persistent pulmonary hypertension. Recent experimental studies suggest that surfactant deficiency may also contribute to CDH pathophysiology. In this report, the authors immunohistochemically and morphometrically examined whether or not the hypoplastic lungs of CDH are associated with the immaturity of the surfactant system, especially alveolar type II cell function. Nine autopsy cases with CDH were immunohistochemically examined for the expression of surfactant apoprotein, using anti-IgG against human surfactant apoprotein A (SP-A), and the findings were compared with those in a gestational and postnatal age-matched control group. The lung/body weight ratio in the CDH was less than that in the controls (0.010 ± 0.005 versus 0.021 ± 0.013, P < .01). The radial alveolar count (RAC) of the CDH cases were also significantly less than that of the control cases (2.10 ± 0.52 versus 3.48 ± 0.39, P < .01). In the CDH cases, the RAC of the lung on the affected side were also significantly less than that of the lung on the unaffected side (1.71 ± 0.34 versus 2.50 ± 0.26, P < .01). In the immunohistochemical distribution of SP-A, compared with the control cases, the number of SP-A-positive cells on the alveolar septa of the CDH cases decreased in number, and this immunohistochemical reaction was weak even in positive type II cells. In addition, the immunoreaction observed in the alveolar type II cells of the unaffected side lungs in the four CDH cases was stronger than that of the unaffected side lungs. These results suggest that in the lungs of the CDH cases, especially on the affected side, there is a possible delay in both the structural growth and functional maturation or development of SP-A synthesis by alveolar type II cells, and this retardation of the functional maturation in alveolar type II cells is also considered to play a role in postnatal respiratory insufficiency in CDH patients.

T lymphocytic and immature macrophage alveolitis in active pulmonary tuberculosis.

The phenotype of bronchoalveolar cells from 11 healthy subjects and from affected and unaffected lungs of 15 patients with pulmonary tuberculosis (PTB) was determined. An immature macrophage alveolitis was found in the affected lung and the unaffected lung versus controls as determined by morphology and peroxidase activity. T lymphocytic alveolitis also was found in the affected but not the unaffected tuberculous lung compared with healthy controls. The majority of alveolar lymphocytes in unaffected and affected PTB lungs were T cells expressing the alpha beta T cell receptor. Alveolar T cells from both unaffected and affected lungs were activated, as determined by increased expression of CD69 and HLA-DR. Interleukin-2 receptor (IL-2R alpha) expression was, however, unchanged on alveolar lymphocytes from affected lung and was decreased in the unaffected lung. Thus, activated T lymphocytes and immature macrophages in the tuberculous lung are basic to the local immunopathogenesis of PTB.

Analysis of a Type D Retroviral Capsid Gene Expressed in Ovine Pulmonary Carcinoma and Present in Both Affected and Unaffected Sheep Genomes

Ovine pulmonary carcinoma is a contagious neoplastic disease of sheep which can be transmitted experimentally with cell-free filtrate. Products homologous to structural proteins of type D and type B retroviruses are expressed in the tumors, but an infectious retrovirus has yet to be isolated. Retroviral RNA was isolated from an affected Peruvian sheep and used as a substrate for reverse transcription. The DNA obtained was subjected to polymerase chain reaction amplification using degenerate primers designed to amino acid sequences shared by the capsid peptides of the viruses that cross-react with the proteins found in the tumor tissues. A retroviral capsid region of type D lineage was isolated that proved to be highly homologous to the jaagsiekte sheep retrovirus isolated from affected sheep in South Africa. This capsid sequence was used to detect the virus in the genomes of sheep with and without ovine pulmonary carcinoma. More than 20 endogenous sequences that hybridized with the probe were found in the sheep examined, and assortment of these could be followed in sheep families. Initial experiments did not show any obvious differences in viral presence in the tumors compared with the background of endogenous viral sequences in unaffected lungs.

The effect of positioning on hemodynamics and gas exchange in the critically ill: a review

Positioning of critically ill patients affects hemodynamic and cardiopulmonary outcomes. A review of clinical studies indicates that backrest elevations up to 60 degrees do not affect measurement of intracardiac pressures or cardiac output, but PaO2 may diminish in sitting positions following surgical procedures. In lateral positions, measurement of intracardiac pressures and cardiac output is not recommended, since a uniform reference point has not been identified for lateral positions. In patients with unilateral lung disease, PaO2 increases with the unaffected lung in the dependent position. Despite widespread use, the Trendelenburg position has not been shown to provide consistent beneficial effects. Prone positioning may be beneficial in adult respiratory distress syndrome and in weaning of mechanically ventilated patients. When planning positioning maneuvers, critical care nurses should consider these effects in relation to the specific needs of each patient. Hemodynamic and cardiopulmonary responses to positioning should be evaluated in conjunction with other therapeutic modalities such as those designed to preserve skin integrity and improve comfort.

CCRT for non-small cell lung cancer: Sensitivity of clinical gains to organ tolerance restrictions

A method is described for allowing the entrance angles of beams to vary along the longitudinal axis of the target volume using a computer controlled radiation therapy (CCRT) treatment technique. The increase in tumor dose potentially available with this technique is evaluated for the case of a non-small cell carcinoma of the lung for which treatment is constrained by a clinically relevant tolerance condition. Tolerance is expressed in terms of that volume of unaffected contralateral lung allowed to receive > 20 Gy. The evaluation is repeated with small changes made to the constraining condition in order to explore the sensitivity of the dose gain to the definition of tolerance. For the chosen example, at least an additional 10 Gy could be prescribed to the tumor with the CCRT technique when the 20 Gy contralateral lung volume was held to less than 30%. A gain of 7 Gy was found when the 20 Gy volume was held to 27% and 1 Gy when the 20 Gy volume was reduced to 25%. CCRT treatment can result in a significant dose gain under a clinically relevant condition for tolerance. Its measured advantage strongly depends on the dose constraints specified. Sensitivity analysis is necessary to meaningfully evaluate the merits of alternative treatment techniques.

BAL modifications after antiblastic and immunomodulant therapy in lung cancer.

The bronchoalveolar compartment can be easily investigated with BAL (bronchoalveolar lavage) before and after antiblastic therapy. We studied 50 patients affected by primary lung cancer, of whom 31 served as a control group and 19 were submitted to BAL after chemo- and/or radiotherapy. Data from BAL performed in an unaffected lung area show that antiblastic therapy can produce alterations in the terminal airways without clinical evidence. Chemotherapy causes a significant impairment of the alveolo-capillary barrier. Radiotherapy is able to affect lymphocytes, with a CD4/CD8 reduction. The concomitance of both therapies produces synergistic effects. Immunomodulant therapy with thymostimulin in otherwise untreated lung cancer patients seems able to modify alveolar lymphocyte number and subsets, but these are preliminary data which need further substantiation.

Warm ischemia induces alteration in lung immune cell functions

Warm ischemia is an important factor in early allograft dysfunction. To elucidate cellular events involved in such lung injury, we examined the effects of warm ischemia on the cytotoxic function of lymphocytes retrieved by bronchoalveolar lavage as compared with peripheral blood lymphocytes. Warm ischemia of the lung was induced in eight dogs by crossclamping left hilar structures for 1 hour. Bronchoalveolar cells from ischemia left and unaffected right lungs, as well as blood lymphocytes, were isolated before operation and 2 hours, 72 hours, and 7 days after operation. Lung and blood lymphocytes were assayed for natural killer and lectin-dependent cell-mediated cytotoxicity. Warm ischemia resulted in a significant impairment of natural killer activity within 2 hours of reperfusion (49% of preoperative control cytolysis, p less than 0.01). There was a significant increase in natural killer activity in bronchoalveolar lavage mononuclear cells 72 hours after reperfusion injury (178.4% of preoperative value, p less than 0.01). Interestingly, these functional alterations were not paralleled with changes seen in the peripheral blood lymphocytes or the opposite nonaffected lungs, where the natural killer activity appeared significantly depressed at 72 hours. Similarly, lectin-dependent cell-mediated cytotoxicity was noted to be increased in the bronchoalveolar lavage from the ischemic lung (179.5%, p less than 0.01) but decreased in the bronchoalveolar lavage from the nonaffected lung and peripheral blood lymphocytes at 72 hours after injury. We conclude that warm ischemia is associated with a functional alteration of the local lung immune cells. Such alteration is not observed in cells from the opposite lung or peripheral blood. The observed increase in nonspecific cytotoxicity of bronchoalveolar lymphocytes can be causative in the early damage seen in poorly preserved lung allografts.

The bronchoalveolar lavage fluid cell analysis with normal lung and unaffected side lung of patients with minor symptoms or radiologic abnormalities.

Bronchoalveolar lavage had been done as the treatment of some diseases such as alveolar proteinsois, bronchiectasis, and severe asthma to remove excessive secretion or mucus. But in the recent decade it has been done as a diagnostic method and a tool to understand and evaluate the pathophysiology of diffuse interstitial lung diseases such as sarcoidosis, pneumoconiosis and hypersensitivity pneumonitis. To analyse the bronchoalveolar fluid, it might be useful to have a standard reference (especially cell counts and differetial count of the cells from bronchoalveolar lavage fluid) of normal person. But it is difficult to study the normal volunteers. We investgated the bronchoalveolar lavage fluid of 48 patients (28 nonsmokers, 20 smokers) who visited Severance Hospital because of minor pulmonary symptoms such as cough and sputum. They did neither complain of dyspnea nor cyanosis, and had normal or unilateral minor lesion on physical examination and chest X-ray. We analysed the recovery rate, viability, total cell count and differential count of the cells in fluid obtained by bronchoalveolar lavage. The following results were obtained: 1) Age ranged from 17 to 72 years-old with the mean age of 36.7; there was no difference of age between the nonsmoker and the smoker gorup. Male to female ratio was 2.43:1 for total group, 1.15:1 for nonsmokers, and 19:1 for smokers. 2) The diagnoses of the patients were undetermined in 41.9%, healed pulmonary tuberculosis in 37.5%, laryngitis or pharyngitis in 10.4% and others in 10.4%. 3) Total cell number of the recovered fluid by bronchoalveolar lavage was significantly higher in male[] than in female[](p vs ]. 4) The differential count of the cells from bronchoalveolar lavage fluid had no difference between the nonsmokers and the smokers. 5) There was no correlation between the total cell count and smoking or age. 6) In the smoker group, there was no correlation between the amount of smoking and the total cell count of the bronchoalveolar fluid. In conclusion, it should be careful to regard the patients with symptoms or minor radiologic abnormalities as a control group in bronchoalveolar lavage study and further study of cell analysis in bronchoalveolar lavage will be needed between smoker and nonsmoker in the male and female healthy people.

Altered cellular immune function in the atelectatic lung

Pulmonary atelectasis is common and may predispose the lung to infection. We have previously shown that atelectasis impairs alveolar macrophage antibacterial function. This study examines the effect of atelectasis on the cytotoxic function of lymphocytes harvested from the bronchoalveolar space of atelectatic lung segments by bronchoalveolar lavage. Specifically, we studied natural killer and lectin-dependent cell-mediated cytotoxicity in peripheral blood and bronchoalveolar lavage lymphocytes from the atelectatic lower lobes and contralateral normal lobes in a group of 8 dogs. We observed a decline of natural killer and lectin-dependent cell-mediated cytotoxicity to 62.7% and 61.5%, respectively, of preatelectasis control values in the affected lung lobes ( p < 0.01). Simultaneous measurements of cytotoxic activity of bronchoalveolar lavage lymphocytes harvested from the unaffected contralateral normal lungs were comparable with control values. On the other hand, natural killer and lectin-dependent cell-mediated cytotoxicity activities in peripheral blood lymphocytes were significantly increased in animals having right lower lobe atelectasis (166.7% and 154.7% of pretreated normal control, respectively, p < 0.01). Atelectasis was also associated with an influx of polymorphonuclear leukocytes into the bronchoalveolar compartment. These findings confirm the presence of natural killer cells and cytotoxic lymphocytes in the bronchoalveolar compartment and demonstrate an atelectasis-induced impairment of local bronchoalveolar lymphocyte function. Such a dysfunction of local lung cellular host defenses may render the atelectatic lung susceptible to infection.

Immunohistochemical Evidence that Lung Carcinomas Grow on Alveolar Basement Membranes

We studied 28 lung carcinomas representing different histological types and three of their regional lymph node metastases immunohistochemically by using specific antibodies against two basement membrane proteins--the 7S domain of type IV collagen and the P1 fragment of laminin. One feature common to all peripherally growing tumors, regardless of the histologic type, was an intact basement membrane between the tumor and the unaffected lung tissue. At these locations, the basement membrane was organized into alveolar structures that did not differ from normal lung tissue. The fibrotic central areas of the tumors did not exhibit this phenomenon. Based on these findings, we believe that malignant tumors of the lung utilize preserved alveolar basement membranes for their local spread. This finding seems to represent a general property of all lung carcinomas, not only adenocarcinomas of the bronchiolo-alveolar type.

Differential evaluation of bronchoalveolar lavage cells and leukotrienes in unilateral acute lung injury and ARDS patients.

Patients with unilateral acute lung injury (UALI; n = 6) and ARDS (n = 4) were evaluated by bronchoalveolar lavage, as controls we used 5 patients suffering from cerebral hemorrhage and without pulmonary, cardiac or infectious disease who were mechanically ventilated. For each group of patients two independent bronchoalveolar lavages (BAL) were performed. The BAL fluid recovered from the two lungs was immediately analyzed for leukotrienes (LTS) by means of RP-HPLC and stained for cell counts. The BAL from the control group did not show any LTS and the percentage of neutrophils was within the normal range: 1 +/- 0.2% right lung and 1.2 +/- 0.4% left lung. The BAL fluid from UALI patients showed two different patterns, the injured lung showed high levels of LTS (39.1 +/- 8 ng ml-1 LTB4; 25 +/- 6 ng ml-1 LTD4 and 27.8 +/- 8.2 ng ml-1 11-trans LTC4) and an increased percentage of neutrophils (74.2 +/- 7%) compared to controls. Only 2 out of the 6 patients from the UALI group showed small amounts of LTB4 (4 ng ml-1) and LTD4 (3.2 ng ml-1). The BAL obtained from the "healthy lung" in both cases showed values of LTS almost eight fold lower than those present in the injured lung. The percentage of neutrophils from the unaffected lungs (4.3 +/- 7%) was not significantly different from controls. Lavage fluid from ARDS patients showed a similar picture to that of the affected lung from UALI patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential ventilation with low-flow CPAP and CPPV in the treatment of unilateral chest trauma

A case of severe unilateral chest trauma with bronchopleural fistula is presented. Ventilatory therapy consisted of asynchronous independent lung ventilation (AILV). The injured lung was ventilated with intermittent positive pressure ventilation (IPPV) [tidal volume (TV) = 200 ml, f = 25/min, I:E = 0.5, minute volume (MV) = 5.0 l/min, FiO2 = 0.4], and the unaffected lung was ventilated with continuous positive pressure ventilation (CPPV) (TV = 600 ml, f = 12/min, I:E = 0.5, MV = 7.2 l/min, PEEP = 0.5 kPa, FiO2 = 0.4). Adequate gas exchange was obtained (PaO2 = 14.5 +/- 2.3 kPa, PaCO2 = 5.5 +/- 0.7 kPa), but high air leakage volumes persisted. Thus, differential low-flow CPAP (V = 5.0-7.5 l/min, PEEP = 0.5 kPa, FiO2 = 0.4) of the injured lung and CPPV (TV = 600 ml, f = 12/min, MV = 7.2 l/min, I:E = 0.5, PEEP = 0.5 kPa, FiO2 = 0.4) of the unaffected lung was applied for 36 hours. Further deterioration of pulmonary function was prevented, and the bronchopleural fistula closed after several hours. After another period of AILV the patient was treated with conventional mechanical ventilation, and finally weaned with high-flow CPAP.

Cilia-associated respiratory (CAR) bacillus infection of obese mice.

Cilia-associated respiratory (CAR) bacillus was identified in respiratory tract lesions of obese mice dying of chronic respiratory disease. Neither Mycoplasma pulmonis nor pathogenic bacteria were isolated from cultures of the lesions at necropsy, but there was serologic and histologic evidence of respiratory virus infection. Cranial-ventral areas of lung were firm and demarcated from unaffected lung at gross examination, and representative tissue sank in water. Microscopically, there was suppurative bronchopneumonia with extensive peribronchiole lymphocyte and plasma cell proliferation. The affected bronchiole epithelium was covered with a sheet of slightly basophilic, filamentous, gram negative bacteria. Bronchioles with lesser amounts of lymphocyte accumulations contained lesser amounts of filamentous bacteria. Bronchioles without filamentous bacteria lining the respiratory epithelium lacked peribronchiole lymphocyte accumulations. There was a high correlation between CAR bacillus-positive serology and the identification of diagnostic histologic lesions. CAR bacillus was readily stained using immunohistochemical methods, and the ultrastructural features were similar to that described in rat infections.

Lung function in newborn infants with tachypnea of unknown cause.

Twenty-one infants with tachypnea (f greater than 60/min) lasting more than 2 h and diagnosed as mild respiratory disease or pulmonary maladaptation according to previously presented criteria were studied during the course of the disease and after clinical recovery. Lung physiology (total and alveolar ventilation, efficiency and distribution of ventilation, functional residual capacity, and lung mechanics) was studied in combination with clinical data. The pathophysiological findings were characterized by increased total ventilation but normal alveolar ventilation, reduced efficiency of ventilation but more even distribution of ventilation (nitrogen elimination pattern) during disease than after clinical recovery, hyperinflation, reduced dynamic lung compliance but unaffected specific lung conductance. Infants with low gestational ages were most severely affected and had longer duration of disease than full-term infants. Our findings suggest that this condition is caused by small airway disease. Disturbances in normal pulmonary adaptation with abnormal retention of lung fluid is the most probable cause.

Interstitial fibrosis and collateral ventilation

Interstitial fibrosis may increase resistance to collateral flow (Rcoll) because of decreased lung volume and destruction of collateral channels or it may decrease Rcoll because of emphysematous changes around fibrotic regions. In addition, if interstitial fibrosis involves a small region of lung periphery, interdependence from surrounding unaffected lung should produce relatively large changes in volume of the fibrotic region during lung inflation. We studied the effects of interstitial fibrosis on collateral airflow by measuring Rcoll at functional residual capacity (FRC) in nine mongrel dogs before and 28 days after the local instillation of bleomycin into selected lung segments. In six of these dogs Rcoll was also measured at a higher lung volume (transpulmonary pressure = 12 cmH2O above FRC pressure). Rcoll increased in fibrotic lung segments following local treatment with bleomycin. With lung inflation (high transpulmonary pressure) Rcoll fell a similar proportion in fibrotic and nonfibrotic lung regions. These observations suggest that collateral resistance increases in fibrotic segments because lung volume decreases or because collateral pathways are involved directly in the fibrotic process. Compensatory increases in collateral communications do not occur. In addition, pulmonary interdependence does not cause disproportionate increases in volume and decreases in Rcoll of the fibrotic region during lung inflation.

Comparison of virulence of ovine respiratory mycoplasmas in the mouse mammary gland

The virulence of isolates of Mycoplasma ovipneumoniae and M. arginini from pneumonic and unaffected ovine lungs was compared in a mouse mammary gland model. The isolates varied in their ability to induce a neutrophilic response in the mammary gland. A moderate to severe form of mastitis was induced by 3 M. ovipneumoniae isolates recovered from pneumonic lungs, while the remaining M. ovipneumoniae isolates from pneumonic lungs and those from unaffected lungs induced a very mild histopathological response. The severity of the mastitis could not be increased by the simultaneous inoculation of a mixture of 5 mycoplasma isolates. Mycoplasma arginini isolates induced only a very mild histopathological response despite having been isolated from pneumonic lungs. The finding that the 3 most virulent M. ovipneumonia isolates were initially recovered from pneumonic ovine lungs suggested that these virulent isolates may contribute to ovine pneumonia. However, the isolation of M. ovipneumoniae from pneumonic ovine lungs does not necessarily imply that these organisms are the causal agents, since M. ovipneumoniae isolates may vary in virulence.

Familial Chronic Lymphocytic Leukemia234

Chronic lymphocytic leukemia (CLL) was previously documented in a father and 4 of his 5 offspring. Follow-up studies revealed spontaneous regression of the disease in 1 patient and shifts in the clinical patterns in the other patients; the unaffected sibling developed lung adenocarcinoma. Cell surface analysis showed that 2 of these patients shared a common surface immunoglobulin profile with mu- and delta-type heavy chains and kappa-type light chains, whereas a 3d sibling with CLL had elevated mu- and kappa-chains. The patient with spontaneous disease remission had a perturbation in the percentage of cells bearing these same markers, consistent with a subclinical persistence of her lympho-proliferative process. Immunogenetic markers were associated with the occurrence of CLL, but these B-cell alloantigens were not linked to HLA. Two patients had abnormalities of chromosome 12 in B- but not T-cells: One had trisomy 12; the other had a mixture of dicentrics and translocations involving the same chromosome.

The pathology of experimental Corynebacterium equi infection in foals following intrabronchial challenge.

Six foals were inoculated intrabronchially with a suspension of Corynebacterium equi. Six weeks before this challenge, three foals were vaccinated with a C. equi bacterin. Three foals were unvaccinated controls. All foals developed a severe bronchopneumonia in the inoculated lung, indicating that vaccination was not protective. Three foals (two vaccinated, one control) were killed eight to nine days after infection. One control died on day 9 with lesions of disseminated intravascular coagulation. The remaining two foals (one vaccinated, one control) were killed on day 17. C. equi was cultured in large numbers from affected lung and bronchial lymph nodes, and in smaller numbers from unaffected lung, spleen, and liver in all foals. In the 8- to 9-day-old lung lesions, the alveoli were filled with macrophages, neutrophils, and multinucleate giant cells and most contained numerous C. equi. The few foci of alveolar necrosis were associated with groups of bacteria-laden macrophages undergoing degeneration. In the lesions of 17-day duration, there was extensive parenchymal destruction with little fibrous tissue reaction. Lesions common to both groups included hyperplastic bronchiolitis, pulmonary edema, and perivascular lymphocytic cuffs and a pyogranulomatous lymphadenitis in bronchial nodes. One vaccinated foal had a microscopic pyogranulomatous colitis. The lesions in the experimentally infected foals are compared with those in naturally infected foals and discussed in terms of likely pathogenetic mechanisms involved in C. equi pneumonia in foals.

MEASUREMENT OF PULMONARY ERYTHROMYCIN CONCENTRATION IN PATIENTS WITH LOBAR PNEUMONIA BY MEANS OF POSITRON TOMOGRAPHY

The concentration achieved in the infected tissue is of fundamental importance in the use of antibiotics. Erythromycin labelled with the positron-emitting nuclide carbon-11 and positron tomography were used to compare local concentrations of this antibiotic in the pneumonic and unaffected lungs of five patients with lobar pneumonia. The time course of uptake of erythromycin into the extravascular compartment (i.e., the intracellular, interstitial, and alveolar compartments) of the pneumonic lung was measured. The mean extravascular concentrations obtained during the first hour after an intravenous injection of 270 mg erythromycin lactobionate were similar in the pneumonic lung and the unaffected lung (5·5±2·2 and 6·6±2·2 μg/g, respectively). An effective concentration of erythromycin was reached in the pneumonic lung within 10 min of the injection and was maintained throughout the period of measurement (60 min).