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Biomedical subjects

R J Lemen

Publications and source records attributed to R J Lemen.

At least 19 recordsLinked to original sources
PubMed2001

Respiratory syncytial virus immune globulin: decisions and costs.

A decision analysis was used to evaluate the economic effectiveness of respiratory syncytial virus immune globulin (RSVIG) prophylaxis on selected pediatric populations at risk for developing RSV bronchiolitis or all respiratory illness-related hospitalizations. We compared costs, outcomes, and cost-effectiveness of administering RSVIG to no treatment in different pediatric populations, including those at risk of developing RSV-bronchiolitis and those at risk of developing any respiratory illness-related hospitalization. We observed that if only infants at high risk of severe RSV infections received treatment with RSVIG, a calculated cost saving of about 27,000 dollars per hospitalization prevented were realized. If the Food and Drug Administration (FDA)-approved indications for RSVIG were followed, the cost to prevent one hospitalization due to RSV bronchiolitis would be over 53,000 dollars. If the aim, however, was to prevent all respiratory illness-related hospitalizations for this broader population, a much lower cost (4,000 dollars) to prevent one hospitalization would result. In this situation, cost neutrality was possible, with a therapy cost of 2,843 dollars compared to the actual average therapy cost of 4,444 dollars. Sensitivity analysis showed that the model was relatively insensitive to all variables, with the exceptions of costs related to RSVIG and intensive care unit (ICU) admissions. We conclude that RSVIG resulted in cost savings if therapy were reserved for the infants who are at highest risk for developing severe RSV infections. RSVIG is not cost-effective for preventing RSV bronchiolitis when used according to the FDA-approved indications. Education that emphasizes frequent hand-washing, avoidance of passive smoking, and lessening exposure to sick children remains the least expensive prevention tool.

Antibodies, Monoclonal↗
PubMed1997

Respiratory syncytial virus bronchiolitis.

Respiratory syncytial virus (RSV) bronchiolitis is associated with the clinical signs and symptoms of small airway obstruction. A major public health problem throughout the world, this condition is responsible for significant morbidity and mortality. Management is primarily preventive, through strict hand washing, avoidance of exposure during the respiratory illness season and intravenously administered prophylactic anti-RSV Immune globulin, especially in selected small infants with underlying cardiopulmonary disease. Supportive measures, including fluid hydration, good nutrition, aerosolized bronchodilators and steroids, may be helpful. Ribavirin may be useful in severely ill children or those with underlying cardiopulmonary disease. A significant number of patients have recurrent episodes of bronchiolitis and wheezing, and may develop asthma later in life. Avoidance of exposure to tobacco smoke, cold air and air pollutants is also beneficial to long-term recovery from RSV bronchiolitis. A number of vaccines to prevent this infection are currently being studied.

Bronchiolitis↗
PubMed1997

Fractal analysis of lung alveoli during the acute phase vs. repair phase of an adenoviral infection in canines.

Acute viral respiratory infections are commonly associated with alterations in lung growth. Recently, fractal techniques have been demonstrated to show changes in alveolar perimeter after canine adenovirus type 2 (CAV2) infection in a beagle puppy model. In the present study, we investigated whether the fractal dimension (Df) of the alveolar perimeter was changed in the acute phase (2-3 weeks after inoculation, 131d CAV2 group) or during the recovery phase (approximately 22 weeks after inoculation, 235d CAV2 group) after a single bout of CAV2. There were sham CAV2 groups, 130d and 238d controls, corresponding to the CAV2 groups. The Df of alveolar perimeter length was significantly increased in the 235d CAV2 puppies compared to all of the other beagle puppy groups. On the other hand, the fractal dimensions for alveolar perimeter length for the other beagle puppy groups were very similar. In a related human study of patients (age range of 25 h to 19 y, N = 11), who died of non-respiratory causes, showed no consistent change in Df of alveolar perimeter length with normal lung growth and development. We conclude that fractal analysis of alveolar perimeter length can be used as an index of permanent lung injury after insult to the growing lungs.

Acute Disease↗
PubMed1997

Human alveolar fractal dimension in normal and chronic obstructive pulmonary disease subjects.

We have determined that fractal analysis of the alveolar perimeter (Df) changes with aging in human lung tissue in twenty-nine patients, age range of 25 hours to 76 years, who died of non-respiratory related causes. There was a very significant difference (p = 0.0004) in Df between the young (less than 16 years old, N = 9, mean Df of 1.047 [0.01]) and adult (greater than 16 years old, N = 20, mean Df of 1.093 [0.013]) groups. Furthermore, there was a significant difference in Df between the Adult group and the group of patients who died of chronic obstructive pulmonary disease (COPD, N = 10) (p = 0.012). Additionally, the Df values for the COPD and cystic fibrosis (CF, N = 5) groups were virtually identical; 1.061 and 1.070, respectively. Regression analysis showed a significant (p = 0.0041) exponential relationship with a correlation coefficient of 0.59 between aging and Df. We have demonstrated that the correlation between Df and aging in humans is an exponential function and that the end-stage pulmonary diseases of COPD and CF decrease Df.

Adolescent↗
PubMed1993

Fractal and morphometric analysis of lung structures after canine adenovirus-induced bronchiolitis in beagle puppies.

Acute viral respiratory infections are commonly associated with alteration in lung growth and with chronic obstructive disease. However, it is difficult to quantify these changes in lung function. We determined that the recently described techniques of fractal analysis gave additional information about the changes in lung function after viral illness compared to standard morphometric techniques. Fractal and morphometric parameters change with lung growth after acute infection with canine adenovirus type 2 (CAV2, n = 5) or no infection (controls, n = 6) in beagle puppies. Lung pathological studies showed areas of obliterative bronchiolitis and chronic small airways inflammation but no emphysema in the CAV2-infected puppies. Morphometric studies at approximately 236 days of age demonstrated accelerated lung growth in the CAV2-infected dogs as evidenced by significant increases in lung volume (VL) and internal surface area (ISA). Fractal analysis showed an increased fractal dimension (Df) of the alveolar perimeter length in the CAV2 group associated with increased growth that was similar to the percentage change in VL and ISA. These data suggest that a single infection with CAV2 in beagle puppies accelerates lung growth and increases the complexity (Df) of the alveolar structure.

Adenoviridae Infections↗
PubMed1992

Bronchoalveolar lavage fluid cytology reflects airway inflammation in beagle puppies with acute bronchiolitis.

Beagle puppies infected with both canine parainfluenza virus type 2 (CPI2) and Bordetella bronchiseptica (Bb) develop more severe acute bronchiolitis and airways hyperresponsiveness than do those infected with CPI2 or Bb alone. The aim of our study was to characterize the inflammatory response associated with airway hyperresponsiveness, and to determine whether the inflammatory cell response of bronchoalveolar lavage fluid (BALF) reflected changes in the bronchioles in this model. We investigated 25 beagle puppies (ages 76 +/- 5 days, mean +/- SEM) in four groups: controls (n = 6), or puppies inoculated with both CPI2 and Bb (CPI2-Bb) (n = 11), with only CPI2 (n = 4), or only Bb (n = 4). The puppies were killed 3-4 days after inoculation, the lungs excised, the intermediate lobe lavaged, and BALF and the bronchiolar wall tissue examined for neutrophils and other inflammatory cells. Control puppies had no evidence of inflammation. However, the CPI2-Bb puppies had developed cough and rhinitis, positive cultures for CPI2 and Bb, and a neutrophilic cellular response in both the bronchioles and the BALF. Puppies inoculated with only CPI2 or Bb had milder illnesses and no significant bronchiolar and BALF neutrophilic response. For all groups, the severity of bronchiolar wall inflammation correlated with the total number of BALF inflammatory cells, and bronchiolar wall neutrophil counts correlated with the percentage of neutrophils in the BALF. The illness and the airway hyperresponsiveness observed in the CPI2-Bb group were associated with airway neutrophilia. Our studies support the hypothesis that neutrophils are associated with airway dysfunction in this model, and the use of BALF to study the process.

Acute Disease↗
PubMed1992

Aerosolized lipopolysaccharide increases pulmonary clearance of 99mTc-DTPA in rabbits.

Bacterial endotoxins alter the permeability of endothelium, but little is known of their effect on epithelium. We exposed specific pathogen-free rabbits to aerosolized Pseudomonas aeruginosa LPS or saline and performed serial measurements of RL, Cdyn, BP, WBC count and differential, and platelet counts. Pulmonary 99mTc-DTPA half-life was measured 4, 6, or 8 h after exposure. The animals were sacrificed and BAL performed. Background and PMA-stimulated superoxide production was measured from individual AM using electrooptical determination of reduction of NBT. Lung tissue was processed for light microscopy and ratio of wet to dry weight. 99mTc-DTPA half-life was significantly shorter in LPS-exposed animals at 6 h (p < 0.05) and 8 h (p < 0.001). There were no differences in Cdyn, RL, BP, WBC, differential, platelet, or BAL cell count at any time between groups. No histologic changes or differences in lung wet to dry weight ratios were found. PMA-stimulated AM superoxide production was significantly increased (p < 0.01) in LPS-exposed animals. This effect was time dependent and could be duplicated in AM from control animals following a 4-h incubation with LPS, lavage fluid from LPS-exposed animals, or recombinant murine TNF. These results demonstrate that aerosolized Pseudomonas LPS increases pulmonary epithelial permeability and primes AM superoxide production.

Aerosols↗
PubMed1991

Changes in lung mechanics and histamine responsiveness after sequential canine adenovirus 2 and canine parainfluenza 2 virus infection in beagle puppies.

We determined the effects of an immediately antecedent viral lower respiratory tract infection (LRI) on the severity of clinical illness, changes in lung function and airway histamine responsiveness produced by a subsequent LRI in 9-12 week old beagle puppies inoculated with canine adenovirus 2, followed in 2 weeks by inoculation with canine parainfluenza 2 virus (CAV2-CP12, n = 7). We compared their acute responses to puppies infected with CP12 alone (n = 5), CAV2 alone (n = 7), and no infection (control, n = 6). Puppies inoculated with either virus alone developed a LRI 3 to 6 days after inoculation which resolved by 12-14 days after inoculation. However, the illness was more severe in the CAV2 group. In the CAV2-CP12 group, CP12 infection following CAV2 infection resulted in a clinical illness nearly comparable to that observed with CAV2 alone. Whereas in control and CP12 puppies, lung resistance (RL) decreased and dynamic lung compliance (Cdyn) increased during the study due to normal growth, RL increased and Cdyn remained unchanged in the CAV2 group. In contrast, RL did not change and Cdyn increased in the CAV2-CP12 group. Airway histamine responsiveness in the CAV2-CP12 group increased during infection with CP12 and was similar to that observed with CAV2 alone. In contrast, infection with CP12 alone produced a small, but non-significant increase in histamine responsiveness. The duration of the increase in histamine responsiveness was not prolonged in the CAV2-CP12 group in comparison to CP12 or CAV2 alone. However, the length of clinical illness was extended in the CAV2-CP12 group in comparison to the other infected groups. These data suggest that an immediately antecedent viral LRI can potentiate the clinical and physiologic effects of a subsequent viral LRI.

Adenoviridae Infections↗
PubMed1991

Canine parainfluenza type 2 and Bordetella bronchiseptica infection produces increased bronchoalveolar lavage thromboxane concentrations in beagle puppies.

Acute infections in beagle puppies with canine parainfluenza virus type 2 (CP12), and CP12 in combination with Bordetella bronchiseptica (Bb) produce bronchiolitis and increased airways responsiveness to aerosolized histamine during the acute infection. In order to determine whether these observations were associated with increased levels of eicosanoids, the stable metabolites of thromboxane A2 and prostacylin, thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF 1 alpha) respectively, and leukotriene B4 were measured in the bronchoalveolar lavage (BAL) fluid of 25 beagle puppies (age = 76 +/- 1 days, mean +/- SEM) 3-4 days after no infection (control, n = 6), inoculation with both CP12 and Bb (CP12-Bb, n = 11), inoculation with CP12 alone (CP12, n = 4), and inoculation with Bb alone (Bb, n = 4). In addition, plasma levels of TXB2 and 6-keto-PGF1 alpha were measured before and after infection in the CP12-Bb and control groups. The BAL concentration of thromboxane B2 was increased in the CP12-Bb group (520 +/- 120 pg/ml), but not in the CP12 (88 +/- 40 pg/ml), Bb (235 +/- 100 pg/ml), or control groups (120 +/- 60 pg/ml, p less than 0.01). There also was a borderline increase in BAL concentration of LTB4 in the CP12-Bb group. No differences were observed in the BAL concentration of 6-keto PGF1 alpha. Furthermore, neither TXB2 nor PGF1 alpha was elevated in the plasma of control or CP12-Bb puppies. These data suggest that increased thromboxane concentrations in BAL fluid are associated with histamine hyperresponsiveness during acute infection in the CP12-Bb group.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Effect of smoke inhalation on immediate changes in lung chemical mediators.

We studied the effects of acute smoke exposure on lung and alveolar macrophage (AM) function in New Zealand white rabbits. Six rabbits were exposed to smoke (SE, N = 6) and a control group of rabbits (SS, N = 6) were exposed to sham smoke. The smoke exposure consisted of 60 tidal volume breaths of air and smoke which were aspirated by syringe from a sampling port of a smoke chamber. The smoke was generated by the combustion of 20 ml diesel fuel and 0.2 g polycarbonate plastic shavings. The smoke was administered in 8-9 min. The rabbits were then killed and the lungs were removed for lavage. Acute smoke exposure caused a significant (p = 0.037) increase in bronchoalveolar lavage fluid levels of leukotriene B4 in the SE rabbits; 643 (+/- 30, SEM) pg/ml compared to 539 (+/- 43, SEM) pg/ml for SS rabbits at 3-4 min post-exposure. Lung surfactant, measured as mumoles/kg phosphatidylcholine, was decreased (p = 0.039) in SE rabbits' bronchoalveolar lavage fluid, 1.07 (+/- 0.12, SEM) -vs- 1.45 (+/- 0.15, SEM) for SS. Furthermore, cultured SE alveolar macrophage superoxide secretion after stimulation with phorbol myristate acetate was significantly decreased versus SS alveolar macrophage superoxide values at 40 min in culture. We conclude that acute smoke exposure causes immediate increases in bronchoalveolar lavage fluid levels of LTB4, and decreases in alveolar macrophage superoxide production and lung surfactant. These changes in chemical mediators may contribute to the lung injury caused by the smoke insult.

Animals↗
PubMed1991

Effects of intravenous and aerosolized arachidonic acid on alveolar epithelial permeability in rabbits.

To determine whether arachidonic acid (AA) alters alveolar epithelial permeability, we studied the effect of both continuous intravenous and aerosolized AA on clearance of [99m]Tc-DTPA from lung to blood in rabbits. Although intravenous AA increased prostacyclin production and aerosolized AA decreased systemic blood pressure, neither continuous intravenous nor aerosolized AA augmented alveolar epithelial permeability.

Aerosols↗
PubMed1990

Airflow obstruction after substance P aerosol: contribution of airway and pulmonary edema.

We have studied the effects of aerosolized substance P (SP) in guinea pigs with reference to lung resistance and dynamic compliance changes and their recovery after hyperinflation. In addition, we have examined the concomitant formation of airway microvascular leakage and lung edema. Increasing breaths of SP (1.5 mg/ml, 1.1 mM), methacholine (0.15 mg/ml, 0.76 mM), or 0.9% saline were administered to tracheostomized and mechanically ventilated guinea pigs. Lung resistance (RL) increased dose dependently with a maximum effect of 963 +/- 85% of baseline values (mean +/- SE) after SP (60 breaths) and 1,388 +/- 357% after methacholine (60 breaths). After repeated hyperinflations, methacholine-treated animals returned to baseline, but after SP, mean RL was still raised (292 +/- 37%; P less than 0.005). Airway microvascular leakage, measured by extravasation of Evans Blue dye, occurred in the brain bronchi and intrapulmonary airways after SP but not after methacholine. There was a significant correlation between RL after hyperinflation and Evans Blue dye extravasation in intrapulmonary airways (distal: r = 0.89, P less than 0.005; proximal: r = 0.85, P less than 0.01). Examination of frozen sections for peribronchial and perivascular cuffs of edema and for alveolar flooding showed significant degrees of pulmonary edema for animals treated with SP compared with those treated with methacholine or saline. We conclude that the inability of hyperinflation to fully reverse changes in RL after SP may be due to the formation of both airway and pulmonary edema, which may also contribute to the deterioration in RL.

Aerosols↗
PubMed1990

Changes in lung mechanics and reactivity with age after viral bronchiolitis in beagle puppies.

We measured changes with growth in lung function and airway reactivity after acute canine parainfluenza virus type 2 (CPI2, n = 5), canine adenovirus type 2 (CAV2, n = 7), and sequential CAV2-CPI2 (n = 6) infections or no infection (controls, n = 6) in beagle puppies (age approximately 79 days). In the CPI2 and CAV2 groups, a lower respiratory illness developed by day 3 postinfection with clinical recovery by day 14. In the CAV2-CPI2 group, puppies were inoculated initially with CAV2 and 12 days later with CPI2. In this group, illness persisted until day 14 after infection with CPI2. Lung resistance (RL), dynamic (Cdyn) and static (Cst) lung compliance, functional residual capacity (FRC), and responsiveness to aerosolized histamine were measured before infection and at periodic intervals until 239 +/- 43 days of age. Lung function data were analyzed using a longitudinal random effects model. In all groups, FRC, Cst, and Cdyn increased with age. In all infected groups, the regression slopes for Cdyn were steeper than in controls. RL decreased linearly with age without group slope differences. Histamine reactivity increased with age, but there were no differences in slope among groups. Lung pathological studies showed areas of obliterative bronchiolitis and chronic small airways inflammation particularly in the CAV2 and CAV2-CPI2 groups. Thus, viral bronchiolitis produces chronic small airways inflammation in beagle puppies and alters the changes in lung function occurring with growth. Histamine reactivity increases with age and is not modified by viral infection.

Adenoviridae Infections↗