Hot, humid air increases cellular influx during the late-phase response to nasal challenge with antigen.

BACKGROUND: Inhalation of hot, humid air (HHA: 37 degrees C, > 95% relative humidity (RH)) partially inhibits the early response to nasal challenge with antigen. OBJECTIVE: To investigate whether HHA inhibited the late-phase response to nasal challenge with antigen and increased hyper-responsiveness of the nasal mucosa to histamine. METHODS: Twenty subjects with seasonal allergic rhinitis, outside of their allergy season, participated in a randomized, 2-way cross-over study. The subjects continuously breathed room air (25 degrees C, 30% RH) or HHA delivered via a face mask during the entire experiment. Subjects were challenged intranasally with antigen 1 h after beginning conditioning. The response was monitored by symptoms and nasal lavage at 2-h intervals after the last antigen challenge. Eight hours after antigen challenge, nasal challenge with histamine was performed. RESULTS: Exposure to HHA significantly increased nasal mucosal temperature from baseline without affecting nasal secretion osmolality. HHA significantly inhibited antigen-induced sneezes, congestion, pruritus, and human serum albumin levels during the early response to antigen challenge. HHA exposure, however, was associated with an 8-fold increase in the eosinophil influx and a 15-fold increase in the levels of eosinophil cationic protein during the late-phase response compared to room air. There were no significant differences in nasal hyper-responsiveness to histamine during either exposure. CONCLUSION: HHA partially decreases the early response to nasal challenge with antigen, but dramatically increases eosinophil influx. Increasing eosinophil number had no effects on the hyper-responsiveness to histamine. We speculate that the physical conditions of air differentially impact the stages of allergic inflammation.

The nasal passage of subjects with asthma has a decreased ability to warm and humidify inspired air.

We previously showed that individuals with seasonal allergic rhinitis (SAR) had a reduced ability to condition air, which was improved by inflammation. We hypothesized that individuals with perennial allergic rhinitis (PAR) would condition air like SAR with inflammation. Because individuals with asthma usually have inflammation in the nose, we hypothesized that they would condition air like individuals with PAR. We performed a prospective, parallel study on 15 normal subjects, 15 subjects with SAR outside their allergy season, 15 subjects with PAR, and 15 subjects with asthma. Cold, dry air (CDA) was delivered to the nose and the temperature and humidity of the air were measured before entering and after exiting the nasal cavity. The total water gradient (TWG) was calculated and represents the nasal conditioning capacity. The TWG in the SAR group was significantly lower than that in normal subjects. There were no significant differences in TWG between the PAR and normal groups. Subjects with asthma had a significantly lower TWG than did normal subjects. There was a significant negative correlation between TWG and Aas score in the group with asthma (r(s) = -0.8, p = 0.0007). Our data show that subjects with asthma have a reduced ability of the nose to condition CDA compared with normal subjects, but which is similar to SAR out of season.

Supine position decreases the ability of the nose to warm and humidify air.

We tested the hypothesis that decreasing nasal air volume (i.e., increasing nasal turbinate blood volume) improves nasal air conditioning. We performed a randomized, two-way crossover study on the conditioning capacity of the nose in six healthy subjects in the supine and upright position. Cold, dry air (CDA) was delivered to the nose via a nasal mask, and the temperature and humidity of air were measured before it entered and after it exited the nasal cavity. The total water gradient (TWG) across the nose was calculated and represents the nasal conditioning capacity. Nasal volume decreased significantly from baseline without changing the mucosal temperature when subjects were placed in the supine position (P < 0.01). TWG in supine position was significantly lower than that in upright position (P < 0.001). In the supine position, nasal mucosal temperature after CDA exposure was significantly lower than that in upright position (P < 0.01). Our data show that placing subjects in the supine position decreased the ability of the nose to condition CDA compared with the upright position, in contrast to our hypothesis.

Ceftizoxime-induced hemolysis secondary to combined drug adsorption and immune-complex mechanisms.

BACKGROUND: Immune hemolytic anemia has been associated with the administration of various antibiotics, including cephalosporins. Presented here is a patient who developed severe acute hemolysis while receiving ceftizoxime (Ceftizox, Fujisawa USA), a third-generation cephalosporin. This is the fourth reported case of hemolysis in association with ceftizoxime. In the previous cases, ceftizoxime was shown to induce hemolysis by the immune-complex mechanism. However, in one of those reports, the concentration of drug used to treat the target RBCs in vitro may not have been optimal. CASE REPORT: The patient's antemortem blood samples were analyzed retrospectively for drug-dependent antibodies by the drug-adsorption and immune-complex methods. Antibody class and titer were evaluated. RESULTS: The patient's sample agglutinated RBCs coated with ceftizoxime as well as uncoated RBCs in the presence of ceftizoxime. The antibodies to ceftizoxime were IgM and IgG. CONCLUSION: This is the first report on both the immune-complex and drug-adsorption mechanisms of ceftizoxime-induced hemolysis. The differential diagnosis of a falling Hct in a patient receiving antibiotics should include drug-related hemolysis; once this diagnosis is considered, management includes the appropriate serologic workup, immediate cessation of the implicated drugs, and possible transfusion support.

Elevation of nasal mucosal temperature increases the ability of the nose to warm and humidify air.

The nose functions to warm and humidify inspired air. The factors that influence these functions have been studied to a limited degree. We have developed a method for measuring the temperature and relative humidity of the air before and after nasal conditioning to study nasal function. In this experiment we studied the effects of raising the mucosal surface temperature by immersion of the feet in warm water. Six subjects (avg. age = 27.0 years) were randomized to immersion of the feet in 30 degrees C and 40 degrees C water. The nasal mucosal temperature increased significantly from the 32.2+/-1.3 degrees C during immersion in the 30 degrees C water to the 33.1+/-1.2 degrees C during immersion in 40 degrees water (p < 0.05). No significant difference in nasal volume was noted between the 30 degrees (17.8+/-4.5 cc) and the 40 degrees (17.7+/-5.3 cc) immersions. There was a significant increase in the conditioning capacity of the nose (as measured by total water content of inspired air) in response to cold-air challenge during the 40 degrees immersion (1669+/-312 mg water) when compared to the 30 degrees immersion (1324+/-152 mg water). From these data we deduce that warming of the nasal mucosa improves the ability of the nose to condition inspired air without a significant change in the volume of the nasal cavity.

Natural and induced allergic responses increase the ability of the nose to warm and humidify air.

BACKGROUND: We have previously shown that subjects with seasonal allergic rhinitis out of season had a reduced ability to warm and humidify air compared with normal subjects. OBJECTIVE: We sought to investigate whether allergic reactions induced by either seasonal exposure or nasal challenge with antigen would decrease the capacity of the nose to condition cold, dry air. METHODS: We performed two prospective studies comparing the effects of allergic inflammation, induced by either seasonal exposure or nasal challenge with antigen, on nasal conditioning capacity (NCC). The total water gradient (WG) across the nose was used to represent the NCC. In the first study, the NCC was measured and compared before and during the allergy season in 10 subjects with seasonal allergic rhinitis. In the second study, 20 subjects with seasonal allergic rhinitis were recruited outside of the allergy season. NCC was measured and compared before and 24 hours after challenge with antigen. RESULTS: In the first study, seasonal allergic subjects in season showed a significant increase in NCC when compared with their preseason baseline (total WG in season: 2050 +/- 138 mg vs total WG preseason: 1524 +/- 100 mg; P <.01). In the second study, antigen challenge led to early-phase and late-phase responses. There was a statistically significant increase in NCC 24 hours after antigen challenge compared with that before antigen challenge (total WG after antigen challenge: 1938 +/- 101 mg vs total WG before antigen challenge: 1648 +/- 84 mg; P =.01). CONCLUSION: Allergic reactions induced by either seasonal exposure or antigen challenge increase the ability of the nose to condition inspired air. We speculate that allergic inflammation increases this ability by changing the perimeter of the nasal cavity.

Ipratropium bromide increases the ability of the nose to warm and humidify air.

We have developed a method for measuring the temperature and relative humidity of air prior to and after nasal conditioning and used it to study the effect of treatment with ipratropium bromide on the ability of the nose to condition cold, dry air. We performed randomized, double-blind, placebo-controlled, two-way crossover studies and an open study in nonallergic subjects. The subjects were treated with ipratropium bromide (84 microgram) or normal saline solution sprayed into the nasal cavity 15 min before the measurement of nasal conditioning capacity. Cold, dry air was delivered to the nose via a nasal mask, and the temperature and humidity of air were measured before entering and after exiting the nasal cavity. The total water gradient across the nose was calculated and represents nasal conditioning capacity. Ipratropium bromide treatment significantly increased nasal conditioning capacity when compared with saline. Ipratropium bromide led to less reduction in the cold, dry air-induced decrease in the nasal volume (p < 0.05) without affecting the decrease in nasal surface temperature during cold, dry air exposure (p = 0.3). Our data show that ipratropium bromide increases the ability of the nose to condition cold, dry air. Thus, treating rhinitis with ipratropium bromide should not increase the burden for inspired air conditioning on the conducting pulmonary airways.

Bronchoalveolar lavage fluid from asthmatic subjects is mitogenic for human airway smooth muscle.

Airway smooth muscle proliferation may contribute to the airway wall remodeling seen in asthma. In this study we tested for the presence of airway smooth muscle mitogenic activity in bronchoalveolar lavage (BAL) fluid obtained from 12 atopic asthmatics before and serially after segmental allergen challenge, and from four normal subjects who did not undergo allergen challenge. Mitogenic effect was assessed by coincubating BAL fluid with human airway smooth muscle cells, and measuring its effect on (3)[H]thymidine incorporation and cell number. Induction of ERK phosphorylation and cyclin D(1) protein abundance were also assessed. Compared with serum-free medium alone, BAL fluid obtained from normal subjects increased thymidine incorporation, cell number, ERK phosphorylation, and cyclin D(1) abundance. BAL fluid from asthmatic subjects prior to allergen challenge induced even greater increases in all measures, except for cell number, which was similar to that observed with normal subjects' BAL fluid. Incubation with lavage fluid obtained 48 h after segmental allergen challenge in atopic asthmatics caused yet further increases in thymidine incorporation, cell number, and cyclin D(1) protein abundance. Molecular sieving of prechallenge BAL fluid from three asthmatic subjects demonstrated that mitogenic activity was present exclusively in the > 10 kD fraction. These results provide the first direct demonstration that fluid lining the airways of asthmatics contains excess mitogenic activity for human airway smooth muscle, and that this activity increases further after allergen challenge.

Relationship of cellular transmigration and airway response after allergen challenge.

We examined the relationship between eosinophil migration into the bronchoalveolar space and change in FEV(1) after endobronchial allergen challenge (EBAC) in atopic asthmatic (AA) and atopic nonasthmatic (ANA) subjects. The purpose of this study was to obtain continuous, intrasubject controlled assessment of the relationship between cell migration in control and allergen-challenged segments in the same individuals over 96 h. In AA subjects, the eosinophil (Eos) count in the bronchoalveolar lavage fluid (BALF) increased from a baseline of 7,896 +/- 3,865 to 416,476 +/- 231,012 Eos/ml by 72 h (p = 0.001) in the challenged segment post-EBAC. For ANA subjects, the postsegmental challenge count was 29,874 +/- 474 Eos/ml (p = 0.03 versus baseline and p < 0.05 AA peak versus ANA peak). In both groups, there was a comparable decrease in peripheral blood eosinophil count beginning 5 h after challenge, which resolved at 24 h. In AA subjects, 416,476 +/- 231,012 Eos/ml was obtained from the allergen-challenged segment and 23,522 +/- 8,298 Eos/ml was obtained from the sham-challenged segment (p < 0.001) at 72 h. In contrast, there was no difference in the Eos count obtained from the BALF between the antigen- and sham-challenged segments of ANA subjects. We also found that increased airway neutrophils were present in equal numbers in allergen-challenged and sham-challenged segments in both AA and ANA subjects. We conclude that augmented eosinophil migration after EBAC is a characteristic of atopic asthma and is not present in atopic subjects who do not have asthma. We find that BAL eosinophilia in ANA patients as well as neutrophilia in both ANA and AA subjects are nonspecific consequences of bronchoscopy. Finally, we find no relationship between specific airway eosinophil migration into the BALF and FEV(1) < 72 h after challenge; however, at 96 h, there is a substantial decrease in FEV(1) that accompanies BALF eosinophilia.

The Chicago Asthma Consortium: a community coalition targeting reductions in asthma morbidity.

The problem of asthma in Chicago remains a complex one, and it is too early to know whether any programs and efforts have had a discernible effect, but the Chicago Asthma Consortium continues to expand its membership and to define its mission. The successes have come from harnessing the passion of the individual members to move the projects forward. As the focus of the consortium moves to addressing system-wide problems in asthma care and the delivery of that care, the consortium is undertaking the construction of a guide for future efforts. In this way, the consortium will fulfill its vision of creating a comprehensive, community-wide plan for the management of asthma, impacting on the unacceptable current levels of morbidity and mortality of the disease.

Warming of feet elevates nasal mucosal surface temperature and reduces the early response to nasal challenge with allergen.

BACKGROUND: We have previously shown that hot, humid air partially reduces the early allergic response. Mechanisms for this effect have been suggested, but none has gained universal acceptance. The most likely explanations are a modification of mucosal temperature or a reduction in nasal secretion osmolality. OBJECTIVE: We sought to investigate whether increasing the nasal mucosal surface temperature by immersing feet in warm water (WW) could decrease the immediate nasal response to challenge with allergen. METHODS: We performed a randomized, 2-way crossover study on 14 subjects with seasonal allergic rhinitis outside of their allergy season. They immersed their feet in either WW (42 degrees C) or room-temperature water (RW; 30 degrees C) for 5 minutes before and during nasal challenge with diluent for the allergen extract, followed by 2 increasing doses of allergen. RESULTS: There was a statistically significant increase in nasal mucosal temperature from baseline after warming of feet (WW, 1.9 +/- 0.1 degrees C, vs RW, 0.2 +/- 0.1 degrees C; P =. 001), but there were no significant differences in body temperature (WW, 0.1 +/- 0.1 degrees C, vs RW, 0.4 +/- 0.1 degrees C; P =.1). Net changes from diluent challenge for all parameters were compared between immersion of feet in WW and RW. Immersion of feet in WW significantly inhibited allergen-induced sneezes (WW, 5.7 +/- 1.1, vs RW, 11.6 +/- 3.2; P <.01), human serum albumin levels (WW, 941.7 +/- 172.2 microg/mL vs RW, 1524.8 +/- 220.6 microg/mL; P <.01), and secretion weights (WW, 30.5 +/- 7.2 mg, vs RW, 41.8 +/- 6.8 mg; P <. 01). CONCLUSION: Our data show that warming of feet decreases the early response to nasal challenge with antigen. This inhibitory effect is probably related to the increase in the nasal mucosal temperature.

A technique to measure the ability of the human nose to warm and humidify air.

To assess the ability of the nose to warm and humidify inhaled air, we developed a nasopharyngeal probe and measured the temperature and humidity of air exiting the nasal cavity. We delivered cold, dry air (19-1 degrees C, <10% relative humidity) or hot, humid air (37 degrees C, >90% relative humidity) to the nose via a nasal mask at flow rates of 5, 10, and 20 l/min. We used a water gradient across the nose (water content in nasopharynx minus water content of delivered air) to assess nasal function. We studied the characteristics of nasal air conditioning in 22 asymptomatic, seasonally allergic subjects (out of their allergy season) and 11 nonallergic normal subjects. Inhalation of hot, humid air at increasingly higher flow rates had little effect on both the relative humidity and the temperature of air in the nasopharynx. In both groups, increasing the flow of cold, dry air lowered both the temperature and the water content of the inspired air measured in the nasopharynx, although the relative humidity remained at 100%. Water gradient values obtained during cold dry air challenges on separate days showed reproducibility in both allergic and nonallergic subjects. After exposure to cold, dry air, the water gradient was significantly lower in allergic than in nonallergic subjects (1,430 +/- 45 vs. 1,718 +/- 141 mg; P = 0.02), suggesting an impairment in their ability to warm and humidify inhaled air.

Partial characterization of a novel mitogen-activated protein kinase/extracellular signal-regulated kinase activator in airway smooth-muscle cells.

We demonstrated previously that in bovine tracheal myocytes, pretreatment with either forskolin or histamine significantly reduces both platelet-derived growth factor (PDGF)- and epidermal growth factor- induced Raf-1 activation but fails to inhibit extracellular signal-regulated kinase (ERK) activation substantially, evidence of a Raf-1-independent ERK activation pathway. To identify Raf-1-independent upstream signaling intermediates of mitogen-activated protein kinase/ERK kinase-1 (MEK1), the dual-function kinase required and sufficient for ERK activation in these cells, lysates from forskolin and PDGF-treated bovine tracheal myocytes were resolved using ion exchange chromatography. Kinase activity for MEK1 was assessed by in vitro phosphorylation assay. In all experiments, the major peak of MEK1 phosphorylation activity was detected in fractions 18 through 26 (80 to 160 mM NaCl), with the peak fraction eluting at a NaCl concentration of 140 mM. The ability of these fractions to activate MEK1 was confirmed by examining the phosphorylation of myelin basic protein, a known substrate for ERKs, in the presence of functional MEK1 and ERK1. Fractions containing kinase activity were also probed with antibodies against MEK kinase-1, Raf-1, A-Raf, B-Raf, Mos, and Tpl-2. None of these proteins was detected in fractions containing peak kinase activity, suggesting the presence of a novel PDGF-stimulated, forskolin-insensitive MEK1 kinase. Further separation of fractions holding peak MEK phosphorylation activity by gel filtration suggested an apparent molecular mass of 40 to 45 kD. We conclude that PDGF-induced activation of MEK1 in bovine tracheal myocytes is mediated at least in part by a novel kinase.

Mitogen-activated signaling in cultured airway smooth muscle cells.

Airway hyperresponsiveness and excess smooth muscle mass coexist in patients with asthma and bronchopulmonary dysplasia. This increase in airway smooth muscle mass, which in part relates to smooth muscle proliferation, may increase bronchoconstrictor-induced airway narrowing, even in the absence of excessive force generation. Thus, there is need for a precise understanding of the events involved in airway smooth muscle mitogenesis. This review examines the inflammatory substances and growth factors that induce airway smooth muscle proliferation, and the signaling pathways that may be involved in the transduction of these extracellular signals to the cell nucleus. Also discussed are various antimitogenic substances and potential mechanisms underlying the inhibition of cell proliferation. Central to the discussion are the extracellular signal regulated kinases (ERKs), serine/threonine kinases of the mitogen-activated protein kinase (MAP kinase) superfamily, which upon activation, translocate from the cytoplasm to the nucleus after mitogenic stimulation. Insight gained from studies of cultured airway smooth muscle growth and mitogen-activated signaling may shed light on parallel mechanisms that may operate in asthma and in bronchopulmonary dysplasia, and may lead to therapeutic interventions against airway remodeling.

Children's and women's ability to fire handguns. The Pediatric Practice Research Group.

OBJECTIVES: To evaluate whether strength differences between children and women might keep children from firing handguns and to determine how many young children can fire available handguns. DESIGN: One- and two-index finger trigger-pull strength was tested using a standard protocol. Data on trigger-pull settings of 64 commercially available handguns were obtained. SETTING AND PARTICIPANTS: Convenience sample of well children and their mothers at four Chicago (Ill)-area pediatric practices for health supervision visits, and of siblings of emergency department patients, during an 8-week period. INTERVENTION: None. MAIN OUTCOME MEASURE: One- and two-index finger trigger-pull strength of mothers and children. RESULTS: Twenty-five percent of 3- to 4-year-olds, 70% of 5- to 6-year-olds, and 90% of 7- to 8-year-olds have a two-finger trigger-pull strength of at least 10 lb, the fifth percentile one-finger trigger-pull strength of adult women. Forty (62.5%) of 64 handguns require trigger-pull strength of less than 5 lb; 19 (30%) of 64 require 5 to 10 lb. CONCLUSIONS: Significant overlap exists in the trigger-pull strength of young children and women, limiting the potential use of increased trigger-pull settings to discourage firearm discharge by children. Young children are strong enough to fire many handguns now in circulation.

Bronchoalveolar lavage fluid from immature rats with hyperoxia-induced airway remodeling is mitogenic for airway smooth muscle.

We previously demonstrated that hyperoxia-exposed immature rats develop airway smooth muscle layer thickening; this remodeling appears partially attributable to smooth muscle hyperplasia. In this study, we tested the hypothesis that excess mitogenic activity for airway smooth muscle cells is present within the lungs of hyperoxia-exposed immature rats. We assessed the proliferative effect of bronchoalveolar lavage (BAL) fluid from air- and O2-exposed animals on cultured rat tracheal smooth muscle cells. BAL fluids from air- or O2-exposed immature rats increased DNA synthesis ([3H]-thymidine incorporation at 24 h of incubation) and cell number (compared with DMEM-treated control cells, at 2 days of incubation), but BAL fluid from O2-exposed animals had significantly greater mitogenic effects. This excess mitogenic activity was lipid inextractable and was ablated by trypsin digestion, indicating that at least one polypeptide growth factor was responsible; molecular sieve fractionation demonstrated a molecular weight of > 10 kD. Because platelet-derived growth factor (PDGF) has been identified in other models of hyperoxia exposure, we tested the further hypothesis that PDGF contributes to the observed excess mitogenic activity. Addition of neutralizing anti-PDGF antibodies to BAL-stimulated smooth muscle cultures did not reduce BAL fluid-induced mitogenesis. These data indicate that the lungs of O2-exposed rats contain excess mitogenic activity for airway smooth muscle, attributable to non-PDGF polypeptide growth factors. It is conceivable that this abnormal mitogenic activity contributes to O2-induced airway smooth muscle remodeling observed in immature rats in vivo.

In vivo hyperoxic exposure increases cultured lung fibroblast proliferation and c-Ha-ras expression.

Exposure to hyperoxia has been demonstrated to alter the cell number of lung fibroblasts in vivo. The precise mechanism of lung fibroblast proliferation after hyperoxic exposure has not been elucidated, however. We examined the growth characteristics of lung fibroblasts isolated from 21-day-old rats exposed to air or 100% O2 for 8 days. Cell proliferation was assessed by hemocytometry, [3H]thymidine incorporation, and fractional labeling with the thymidine analog bromodeoxyuridine. Under all conditions tested, fibroblasts isolated from O2-exposed rats grew more rapidly than those from air-exposed rats. Conditioned medium from fibroblasts isolated from hyperoxia-exposed rats failed to increase the [3H]thymidine incorporation of control cells to that observed in cells isolated from hyperoxia-exposed animals, suggesting that an autocrine growth factor was not responsible for the excess proliferation. Sensitivity to exogenous growth factors was assessed by measuring the response to increasing concentrations of insulin-like growth factor-1 (IGF-1). Relative to 1% fetal bovine serum (FBS), concentrations of IGF-1 between 3 and 30 ng/ml significantly increased the [3H]thymidine incorporation of fibroblasts derived from hyperoxic animals, whereas control cells were unresponsive to IGF-1 stimulation. The apparent sensitivity to IGF-1 led us to assess the effect of in vivo hyperoxic exposure on the expression of c-Ha-ras, which encodes a membrane-bound, GTP-binding/hydrolyzing protein essential for progression through G1 in the cell cycle. ras mRNA levels in quiescent, control cells were minimal but increased following serum stimulation. The c-Ha-ras expression of lung fibroblasts from hyperoxia-exposed animals, on the other hand, was substantial in quiescent cells and remained high after serum exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperoxia increases airway cell S-phase traversal in immature rats in vivo.

Exposure of 21-day-old Sprague-Dawley rats to hyperoxia (> 95% O2 for 8 days) causes thickening of the airway epithelial and smooth muscle layers. To test the hypothesis that hyperoxic exposure increases airway layer DNA synthesis, we labeled the nuclei of cells undergoing S-phase by administering the thymidine analog bromodeoxyuridine (BrdU). BrdU was administered on days 3 and 4, 5 and 6, or 7 and 8 of air or O2 exposure, and the lungs were harvested immediately thereafter. Histologic sections were stained with an avidin-biotin-immunoperoxidase stain that revealed BrdU incorporation into nuclei, and a hematoxylin counterstain. After 4 days of air or O2 exposure, there was no difference in BrdU fractional labeling between control and hyperoxic animals. Thereafter, fractional BrdU labeling of the small airway (circumference < 1,000 microns) epithelium and smooth muscle layer was significantly increased in O2-exposed animals (P < 0.01, unpaired t test). The fractional labeling of larger, central airway smooth muscle layer cells was also increased after 8 days of O2 exposure (P < 0.01). In another cohort of O2-exposed animals, measurements of airway layer dimensions demonstrated increases in small airway epithelial and smooth muscle layer thickness that paralleled the time course seen for BrdU incorporation. We conclude that O2 exposure of immature rats increases airway epithelial and smooth muscle layer cellular DNA synthesis. These data suggest that hyperplasia of airway epithelial and smooth muscle layer cells may contribute to hyperoxia-induced airway remodeling.

Pentoxifylline does not protect against hyperoxic lung injury in rats.

Hyperoxia has been used extensively as a model of acute lung injury. The drug pentoxifylline has been shown to have a protective effect in other models of lung injury. We sought to determine whether pentoxifylline protects against hyperoxic lung injury in rats by decreasing the accumulation of neutrophils within the lung. A total of 84 rats were studied. Twenty four rats were randomized into four groups. Two groups of rats were pretreated for 48 h with either pentoxifylline (20 mg.kg-1) or saline, and then exposed to > 95% O2 for 60 h while treatments continued. Two groups of control rats received the same treatment regimens as the O2-exposed animals, but breathed room air. Neutrophil accumulation in the lung was quantified both by histology and myeloperoxidase activity. Lung neutrophil accumulation increased in the oxygen-exposed group receiving pentoxifylline as compared to oxygen- or air-exposed rats receiving saline injections. Total glutathione was higher in lung homogenates from the hyperoxic, pentoxifylline-treated group than in homogenates from the other three groups. To study survival, 60 rats were exposed to > 95% O2 for 120 h, 30 rats were pretreated with pentoxifylline, and 30 received saline. Survival after 120 h of exposure to hyperoxia was not altered by pentoxifylline treatment (pentoxifylline treated: 6 out of 30 survived; saline treated: 2 out of 30 survived). We conclude that pentoxifylline does not reduce mortality or lung injury in rats exposed to hyperoxia and is associated with an increase in lung neutrophil accumulation.