Search

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.

Possible antioxidant effects of pretreatment with vitamin A on bleomycin-induced rat lung injury were studied. Intratracheal bleomycin was administered to rats pretreated with vitamin A (50,000 IU/day) or vehicle control. Analysis of bronchoalveolar lavage fluid (BAL) total and differential cell counts, lung weight, lung pathology, and alveolar macrophage superoxide anion production were performed before and at various time points after the instillation of bleomycin. Bleomycin with vehicle raised total BAL cell count and the per cent of BAL neutrophils at day 7 post injury. The percent of lung involved with pneumonitis, the lung wet weight/body weight ratio and the alveolar macrophage superoxide anion production were also increased after bleomycin alone compared to the group pretreated with vitamin A. Rats pretreated with vitamin A demonstrated a statistically significant reduction in total BAL cell count and in alveolar macrophage superoxide anion production 7 days after bleomycin compared with vehicle control. Lung wet weight/body weight ratio 7 days after bleomycin was reduced in the vitamin A treated rats. There was a trend to less pneumonitis in the vitamin A pretreated group. These data suggest that vitamin A attenuates bleomycin induced pulmonary damage by a mechanism which involves inhibition of bleomycin-induced alveolar macrophage superoxide anion production.

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.

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.

Acute infection with canine adenovirus was studied in 23 specific pathogen-free outbred beagle puppies (median age = 78 days, range = 67 to 86 days) to determine its effects on pulmonary function and airway responsiveness to aerosolized histamine. The following groups were studied: uninoculated (n = 6, Control); inoculated with canine adenovirus type 2 (CAV2) (n = 11, Infected); and subclinical spontaneous infection with CAV2 (n = 6, Subclinical). While anesthetized with chloralose and mechanically ventilated, lung function and responsiveness to aerosolized histamine were measured 3 days before inoculation (Day -3), the day of inoculation (Day 0), and 3 to 4 (Day 3-4), 6 (Day 6), 8 to 10 (Day 8-10), and 12 to 14 (Day 12-14) days after inoculation. Histamine responsiveness was assessed by calculating the provocation concentration of histamine diphosphate to increase lung resistance (RL) to 150% (PC 150% RL), or decrease dynamic lung compliance (Cdyn) to 75% (PC 75% Cdyn) of the response to saline [RL(sal) and Cdyn(sal), respectively]. Arterial blood gases, functional residual capacity (FRC), specific static lung compliance (spCst), RL, Cdyn, and histamine responsiveness were not significantly different on Day 0 among the groups (p greater than 0.05). Control and Subclinical puppies remained healthy, had a mean weight gain of 0.7 kg, and did not change their histamine responsiveness during the study period. Infected puppies developed moderate to severe clinical illnesses, had poor weight gain, and were histamine hyperresponsive on Days 3-4 and 6. One infected puppy died on Day 3-4, and two died on Day 6 of their illness.(ABSTRACT TRUNCATED AT 250 WORDS)

Histamine hyperresponsiveness with viral bronchiolitis may depend on previous exposures to viruses or to other pathogens. We studied 32 outbred beagle puppies 80 to 155 days of age who were raised in isolation and who were specific pathogen-free. Puppies were inoculated with canine parainfluenza type 2 (CPI2, n = 8), Bordetella bronchiseptica (Bb, n = 7), or both CPI2 and Bb (CPI2-Bb, n = 9). Control puppies (C, n = 8) were not inoculated. The puppies were anesthetized with sodium thiopental (5 mg/kg) and chloralose (80 mg/kg) and were ventilated mechanically. Lung resistance (RL), dynamic lung compliance (Cdyn), functional residual capacity (FRC), and responsiveness to aerosolized histamine were measured 3 days prior to inoculation (Day -3), on the day of inoculation (Day 0), and on Days 3-4, 6, 8-10, and 12-14 after inoculation. Histamine responsiveness was measured as: (1) the concentration of histamine base that increased RL to 150% (PC 150% RL) or decreased Cdyn to 75% (PC 75% Cdyn) of the response to saline (RL sal and Cdyn sal, respectively), and (2) the change in RL or Cdyn after inhalation of 11 mg/ml of histamine when compared with RL sal and Cdyn sal. On Day 0 there were no significant (p greater than 0.05) differences among groups with regard to age-corrected weights, FRC, RL, Cdyn, or histamine responsiveness. Control puppies remained healthy, and their pulmonary function and histamine responsiveness did not change. CPI2-Bb puppies increased RL and decreased FRC on Day 3-4, and were moderately ill and histamine-hyperresponsive on Day 3-4 and on Day 6.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied lung clearance of technetium-labeled diethylenetriamine pentaacetic acid [( 99mTc]DTPA), plasma and bronchoalveolar lavage fluid (BALF) concentrations of 6-keto-PGF1 alpha (stable metabolite of prostacyclin, prostaglandin I2, PGI2), TxB2 (stable metabolite of thromboxane A2, TxA2), and leukotriene B4 (LTB4), and inflammatory cells as indices of lung injury in rabbits exposed to cigarette smoke (CSE). Thirty-one rabbits were randomly assigned to four groups: control sham exposure (SS, n = 6), sham smoke ibuprofen-pretreated (SS-I, n = 7), CSE (n = 6), and CSE ibuprofen-pretreated (CSE-I, n = 12). Ibuprofen, a cyclooxygenase eicosanoid inhibitor, was administered as a single daily intramuscular injection (25 mg/kg) for 7 d before the experiment. Cigarette or sham smoke was delivered by syringe in a series of 5, 10, 20, and 30 tidal volume breaths with a 15-min counting period between each subset of breaths to determine [99mTc]DTPA biological half-life (T1/2). The CSE-I group was retrospectively divided into rabbits who survived the 30-breath subset (CSE-IL, n = 6) and those who died during the 30-breath CSE (CSE-ID, n = 6). In the CSE, CSE-IL, and CSE-ID groups, [99mTc]DTPA T1/2 as well as BALF LTB4 levels were significantly decreased. Plasma and BALF 6-keto-PGF1 alpha increased in CSE rabbits compared to the other groups. Alveolar macrophages were lower in the CSE-ID rabbits than in the CSE-IL group. CSE and CSE-IL BALF lymphocyte levels were decreased compared to SS values. Our data indicate that acute CSE is associated with significant increases in 6-keto-PGF1 alpha and decreases in LTB4 as well as a significant reduction in lymphocytes. Furthermore, pretreatment with ibuprofen before CSE was associated with severe lung injury in half of the rabbits. The severity of lung injury may be related to a combination of a lower number of alveolar macrophages and blockade of lung PGI2.

Morphometric analysis of the lungs and heart of a male infant who died at 33 months of age of bronchopulmonary dysplasia after prematurity and respiratory distress syndrome and its treatment is presented. Alveolar internal surface area was 8.4 m2 compared to 15.3-27.8 for age-matched controls. The number of alveoli was 19 x 10(6) (123.3-172.5 x 10(6) for controls); however, the mean small airway diameter, 0.44 mm was normal, and small airway abnormalities were minimal. There was marked muscular hypertrophy of the right ventricle.

The lungs of 9 patients with cystic fibrosis were studied by morphometric techniques to determine the amount of bronchiectasis, emphysema, pneumonia, bronchial gland enlargement, and small airways narrowing and density. The severity of these processes, which should account for the clinical picture of air-flow limitation in these patients, varied greatly among patients of different ages. Bronchiectasis was present in all children, but the amount of bronchiectasis did not appear to increase with age. Mild destructive emphysema was seen only in adults, but many younger patients had overinflation without destructive emphysema, as recognized by increased mean linear intercept (interalveolar distance). Despite clinical evidence of mucous hypersecretion, bronchial gland enlargement was present only in some patients. The younger patient showed normal small airways, but children and younger teenagers tended to have dilated small airways. Older teenagers and adult predominantly had stenosis of small airways. Varying patterns of pulmonary pathology are seen in cystic fibrosis and may be related to rapidity of progression of disease.