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Background: Theophylline and long acting beta-2 agonists are bronchodilators used for the management of persistent asthma symptoms, especially nocturnal asthma. They represent different classes of drug with differing side-effect profiles., Objectives: To assess the comparative efficacy, safety and side-effects of long-acting beta-2 agonists and theophylline in the maintenance treatment of adults and adolescents with asthma., Search Strategy: We searched the Cochrane Airways Group trials register and reference lists of articles. We also contacted authors of identified RCTs for other relevant published and unpublished studies and pharmaceutical manufacturers. Most recent search: November 2006., Selection Criteria: All included studies were RCTs involving adults and children with clinical evidence of asthma. These studies must have compared oral sustained release and/or dose adjusted theophylline with an inhaled long-acting beta-2 agonist., Data Collection and Analysis: In original review, two reviewers independently assessed trial quality and extracted data, similarly in this update two reviewers undertook this. Study authors were contacted for additional information., Main Results: Thirteen studies with a total of 1344 participants met the inclusion criteria of the review. They were of varying quality. There was no significant difference between salmeterol and theophylline in FEV(1) predicted (6.5%; 95% CI -0.84 to 13.83). However, salmeterol treatment led to significantly better morning PEF (mean difference 16.71 L/min, 95% CI 8.91 to 24.51) and evening PEF (mean difference 15.58 L/min, 95% CI 8.33 to 22.83). Salmeterol also reduced the use of rescue medication. Formoterol, used in two studies was reported to be as effective as theophylline. Bitolterol, used in only one study, was reported to be less effective than theophylline. Participants taking salmeterol experienced fewer adverse events than those using theophylline (Parallel studies: Relative Risk 0.44; 95% CI 0.30 to 0.63, Risk Difference -0.11; 95% CI -0.16 to -0.07, Numbers Needed to Treat (NNT) 9; 95% CI 6 to 14). Significant reductions were reported for central nervous system adverse events (Relative Risk 0.50; 95% CI 0.29 to 0.86, Risk Difference -0.07; 95% CI -0.12 to -0.02, NNT 14; 95% CI 8 to 50) and gastrointestinal adverse events (Relative Risk 0.30; 95% CI 0.17 to 0.55, Risk Difference -0.11; 95% CI -0.16 to -0.06, NNT 9; 95% CI 6 to 16)., Authors' Conclusions: Long-acting beta-2 agonists, particularly salmeterol, are more effective than theophylline in improving morning and evening PEF, but are not significantly different in their effect on FEV1. There is evidence of decreased daytime and nighttime short-acting beta-2 agonist requirement with salmeterol. Fewer adverse events occurred in participants using long-acting beta-2 agonists (salmeterol and formoterol) as compared to theophylline.

Background: The pathogenesis of exercise induced bronchoconstriction is likely multifactorial and is not completely understood. Inflammation plays an important role in the pathogenesis of exercise induced bronchoconstriction in asthmatic subjects but the evidence seems less strong in non-asthmatic subjects. The management of exercise induced bronchoconstriction focuses on prevention, through both pharmacologic and non-pharmacologic interventions., Objectives: The objectives of this review were to evaluate the use of inhaled corticosteroids in the treatment of exercise induced bronchoconstriction in a systematic way. Specifically, the review was designed to: determine whether inhaled corticosteroids (compared to placebo) has an attenuating effect on exercise induced bronchoconstriction in adult and pediatric asthmatic patients; estimate the magnitude of the attenuating effect., Search Strategy: We searched the Cochrane Airways Review Group Specialised Register of trials, the Cochrane Central Register of Controlled Trials, review articles, textbooks and reference list of articles., Selection Criteria: Randomised trials in adults or children comparing inhaled corticosteroids with placebo to prevent bronchoconstriction in patients with exercise induced bronchoconstriction., Data Collection and Analysis: Trial quality assessment and data extraction were conducted independently by two reviewers., Main Results: The results from six randomised controlled trials involving 123 participants were analyzed (two trials involving adults and four involving children). Combining results from the two parallel studies with at least 4 weeks duration of inhaled corticosteroids, the use of inhaled corticosteroids significantly attenuated the percent fall index in forced expiratory volume in 1 second (WMD = 14.07%; 95% CI: 11.62% to 16.52%). The result from one crossover study with duration of inhaled corticosteroids of 4 weeks revealed significant attenuation of percent fall in forced expiratory volume in 1 second ( WMD = 6.90%; 95% CI: 1.40% to 12.40%) and the percent fall in peak expiratory flow ( WMD =11.50%; 95% CI: 6.31% to 16.69%). The small amount of data from placebo-controlled trials using a single treatment do not currently allow conclusions to be drawn., Authors' Conclusions: Inhaled corticosteroids used for 4 weeks or more before exercise testing significantly attenuated exercise-induced bronchoconstriction. The relative benefits of inhaled corticosteroids compared to other forms of exercise induced bronchoconstriction treatment (sodium cromoglycate, nedocromil sodium, salbutamol, and other anti-inflammatory agents) remains unclear.

Objective: To elucidate oxygen administration practices in the setting of acute exacerbations of chronic obstructive pulmonary disease (COPD) and compare these practices with those recommended in internationally accepted guidelines., Design: Retrospective audit., Participants and Setting: 65 patients admitted to a Melbourne university teaching hospital via the emergency department (ED), identified through medical records by a discharge diagnosis (discharged between 1 June and 30 September 2005) of acute exacerbation of COPD (AECOPD). Those included had respiratory function test results consistent with British Thoracic Society guidelines for the diagnosis of COPD., Main Outcome Measures: Length of stay, need for high dependency unit (HDU) admission, use of non-invasive ventilation (NIV), and use of arterial blood gas (ABG) tests., Results: Our audit showed that 95% of patients defined as retaining carbon dioxide received oxygen at a flow rate greater than 2 L/min. This process began in the ambulance and continued in the ED, often without monitoring of ABG levels. Length of stay was significantly longer (P = 0.029); need for NIV on admission greater (P = 0.0124); and rate of admission to the HDU higher (P = 0.0124) in patients who achieved a partial pressure of arterial oxygen (PaO(2)) >/= 74.5 mmHg compared with those with a PaO(2) < 74.5 mmHg., Conclusions: The vast majority of patients with AECOPD presenting to our university teaching hospital receive oxygen therapy outside of internationally accepted guidelines, often without monitoring of ABG levels. The use of high-flow oxygen may contribute to an increased length of stay, more frequent admission to HDU and greater use of NIV among patients who achieve a higher PaO(2).

Background: The extent to which overdiagnosis occurs in lung cancer screening programmes has been debated. Overdiagnosis refers to the detection by screening of cancers that would not have become clinically apparent or symptomatic before that individual died of other causes., Methods: A retrospective review of coronial autopsies performed in Victoria between April 1991 and February 2002 was conducted to determine the rate of incidental lung cancer in individuals who died of natural causes., Results: A total of 24,708 autopsy reports were searched electronically. We estimated that in 56% of these death was from natural causes. Amongst individuals who died naturally there were 167 cases of lung cancer, 47 of these were incidental including five carcinoid tumours, three small cell tumours, 11 cases of carcinoma in situ and 28 invasive nonsmall cell lung cancers. Of the incidental invasive nonsmall cell lung cancers, 86% were stage I., Conclusions: Although incidental lung cancer is uncommon, there are some lung cancers that remain undetected during life and do not contribute to death. These findings support the hypothesis that some lung cancers detected by screening may never progress to cause symptoms or death in that individual's lifetime and therefore may be overdiagnosed by screening.

Objective: Lung cancer is a substantial public health problem in Western countries. Evidence from previous controlled trials of chest radiography and sputum cytology does not support lung cancer screening, but computed tomography (CT) screening has recently emerged as a more sensitive screening tool. For the present article, the available observational studies of low-dose helical CT screening for lung cancer were reviewed., Methodology: An evidence-based review of all published observational studies of low-dose helical CT screening for lung cancer, identified by an extensive search of Medline, was conducted., Results: Eight observational studies of CT screening for lung cancer were identified. Relative to chest radiography, low-dose helical CT is a sensitive screening tool and can detect a high proportion of small lung cancers at an early and resectable stage. The yield of sputum cytology in addition to CT screening appears to be relatively low. To date, 5-year lung cancer survival of all individuals participating in baseline screening has not been reported for any of the studies., Conclusions: Although these preliminary studies are very promising, it remains to be proven that the early detection and treatment of lung cancer will lead to a reduction in mortality. This issue will be addressed by randomized controlled trials. In the interim, the long-term follow up of these observational studies could provide further insights.

Background: While population based screening for lung cancer has not been adopted by most countries, it is not clear whether sputum examinations, chest radiography or newer methods such as computed tomography are effective in reducing mortality from lung cancer., Objectives: To determine whether screening for lung cancer using regular sputum examinations or chest radiography or CT chest reduces lung cancer mortality., Search Strategy: Electronic databases (the Cochrane Central Register of Controlled Trials, MEDLINE, PREMEDLINE and EMBASE; 1966 to July 2000) ), bibliographies, hand searching of a journal and discussion with experts were used to identify published and unpublished trials., Selection Criteria: Controlled trials of screening for lung cancer using sputum examinations, chest radiography or CT chest., Data Collection and Analysis: Intention to screen analysis was performed. Where there was significant statistical heterogeneity relative risks were reported using the random effects model, but for other outcomes the fixed effect model was used., Main Results: Seven trials were included (6 randomised controlled studies and 1 non-randomised controlled trial) with a total of 245,610 subjects. There were no studies with an unscreened control group. Frequent screening with chest x-rays was associated with an 11% relative increase in mortality from lung cancer compared with less frequent screening (RR 1.11, CI: 1.00-1.23). A non statistically significant trend was observed to reduced mortality from lung cancer when screening with chest x-ray and sputum cytology was compared with chest x-ray alone (RR 0.88, CI:0.74-1.03). Several of the included studies had potential methodological weaknesses. There were no controlled studies of spiral CT., Reviewer's Conclusions: The current evidence does not support screening for lung cancer with chest radiography or sputum cytology. Frequent chest x-ray screening might be harmful. Further, methodologically rigorous trials are required.

Community-acquired pneumonia is caused by a range of organisms, most commonly Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae and respiratory viruses. Chest x-ray is required for diagnosis. A risk score based on patient age, coexisting illness, physical signs and results of investigations can aid management decisions. Patients at low risk can usually be managed with oral antibiotics at home, while those at higher risk should be further assessed, and may need admission to hospital and intravenous therapy. For S. pneumoniae infection, amoxycillin is the recommended oral drug, while benzylpenicillin is recommended for intravenous use; all patients should also receive a tetracycline (eg, doxycycline) or macrolide (eg, roxithromycin) as part of initial therapy. Flucloxacillin or dicloxacillin should be added if staphylococcal pneumonia is suspected, and gentamicin or other specific therapy if gram-negative pneumonia is suspected; a third-generation cephalosporin plus intravenous erythromycin is recommended as initial therapy for severe cases. Infections that require special therapy should be considered (eg, tuberculosis, melioidosis, Legionella, Acinetobacter baumanii and Pneumocystis carinii infection).

Background: The effectiveness of screening for lung cancer with chest radiography, sputum cytology or spiral CT has not been established., Objectives: To determine whether screening for lung cancer using regular sputum examinations or chest radiography or CT chest reduces lung cancer mortality., Search Strategy: Electronic databases, bibliographies, hand searching of a journal and discussion with experts were used to identify published and unpublished trials., Selection Criteria: Controlled trials of screening for lung cancer using sputum examinations, chest radiography or CT chest., Data Collection and Analysis: Intention to screen analysis was performed. Where there was significant statistical heterogeneity relative risks were reported using the random effect model, but for other outcomes the fixed effect model was used., Main Results: Seven trials were included (6 randomised controlled studies and 1 non-randomised controlled trial) with a total of 245,610 subjects. There were no studies with an unscreened control group. Frequent screening with chest x-rays was associated with an 11% relative increase in mortality from lung cancer compared with less frequent screening (RR 1.11, CI: 1.00-1.23). A non statistically significant trend was observed to reduced mortality from lung cancer when screening with chest x-ray and sputum cytology was compared with chest x-ray alone (RR 0.88, CI:0.74-1.03). Several of the included studies had potential methodological weaknesses. There were no controlled studies of spiral CT., Reviewer's Conclusions: The current evidence does not support screening for lung cancer with chest radiography or sputum cytology. Frequent chest x-ray screening might be harmful. Further, methodologically rigorous trials are required.

Lung cancer is the leading cause of death from cancer in Australian adults. Over 90% of lung cancers are due to exposure to tobacco smoke. Female smokers are more susceptible to developing lung cancer than male smokers. The overall survival of non-small-cell lung cancer is 13%, having increased from 6% over the past 30 years. The development of new, unexplained respiratory or systemic symptoms in a heavy smoker or ex-smoker should raise the suspicion of lung cancer. Early detection and consideration of tumour resection for all operable tumours are the main strategies for improving the cure rate of non-small-cell lung cancer at present. Reducing the prevalence of smoking remains the best method for reducing lung cancer deaths.

This prospective study evaluated pulmonary gas exchange in patients with severe liver disease, its relationship to intrapulmonary shunting, and its response to liver transplantation. Detailed clinical examinations, chest radiographs, and arterial blood gas estimations were performed on 74 consecutive patients before and after liver transplantation. Fifty percent of the 74 patients had a widened alveolar-arterial (A-a) oxygen gradient (> 15 mm Hg) and 45% a reduced PaCO2 (< 35 mm Hg). Twenty-two percent were hypoxemic (PaO2 < 80 mm Hg). Following transplantation mean PaO2 increased (pre-89 +/- 14 vs. post-94 +/- 8 mm Hg; P = .014) and A-a oxygen gradient decreased (pre-16 +/- 14 vs. post-8 +/- 9 mm Hg; P < .001), despite an increase in PaCO2 (pre-36 +/- 5 vs. post-39 +/- 4; P < .001). To examine this improvement in oxygen exchange further, a subgroup of 26 consecutive patients, with no obvious cardiorespiratory cause for abnormal gas exchange underwent, pre- and post-operative spirometry, measurement of carbon monoxide diffusion capacity (DLCO), intrapulmonary shunt estimations (100% oxygen technique), and echocardiography. In this subgroup, 23% were hypoxemic, 54% had a widened A-a oxygen gradient, and 85% had increased intrapulmonary shunting (> 5%) before transplantation. There was a significant correlation between the degree of pre-transplantation intrapulmonary shunting and A-a oxygen gradient (P < .01). Nineteen of the 22 patients with increased shunting improved following transplantation and improved A-a oxygen gradient correlated well with the reduction in shunting (P < .005). DLCO was reduced in 69% of these patients with a mean value of 73% of predicted. However, the post-transplantation mean DLCO did not increase despite the improvement in oxygen exchange. In conclusion, gas exchange abnormalities are common in patients with severe liver disease but these usually resolve post-transplantation. Intrapulmonary shunting is a major determinant of abnormal oxygen uptake in transplant candidates without evidence of cardiorespiratory disease. Finally, the mechanism for the reduced DLCO is unclear but appears different to that responsible for intrapulmonary shunting and abnormal oxygen exchange.

Deletions involving the chromosome 9p21 region have been reported as frequent events in non-small cell lung cancer (NSCLC). To investigate potential tumor-suppressor gene (TSG) loci within the 9p21 region, which also harbors the candidate TSG locus CDKN2a, we studied 32 cases of primary NSCLC for loss of heterozygosity (LOH). Tumor and paired normal lung cells were microdissected from lung tissue imprints and all samples screened using PCR-LOH analysis with 15 9p markers. In addition, 3 NSCLC cell lines and their matched normal lung and tumor DNA were similarly analyzed. LOH at the marker D9S259, which is proximal to the CDKN2a locus, was found most frequently (52%), while LOH at D9S942, the marker closest (5 kb) to the CDKN2a gene, was seen in only 17%. Homozygous loss of markers close to CDKN2a was, however, detected in 2 of the 3 cell lines and one accompanying tumor sample. We propose that a TSG in the region of deletion proximal to the CDKN2a gene within 9p21 may play a significant role in the pathogenesis and progression of NSCLC.

Influenza is a serious cause of morbidity and mortality, particularly in the older adult, and it represents a significant economic burden for health-care services. We have reviewed the published literature relating to influenza vaccine effectiveness and the cost-effectiveness of influenza vaccination in comparison with other health-care interventions and conclude that influenza vaccination is one of the most cost-effective interventions possible in the older adult population.

Non-small-cell lung cancer (NSCLC) accounts for more than three quarters of all lung tumours and is the leading cause of deaths due to cancer in Australia. More than half of the patients with NSCLC present with advanced disease. Radiation therapy has been the mainstay of active treatment for these patients. There is increasing evidence supporting the benefit of chemotherapy as an addition to radiation therapy in locally advanced non-metastatic disease. The use of cisplatin-based chemotherapy prior to radiation therapy would appear to be a new standard of care in patients with stage III B NSCLC. In advanced (metastic) disease, palliation of symptoms remains the major goal of current treatment programmes. This can be achieved with the best supportive care, radiotherapy, and, in selected patients, platinum-based chemotherapy. Clinical trials to test new treatments, with survival, quality of life and cost-benefit as endpoints, are essential. The present study discusses the current status of conventional and newer treatment methods in locally advanced and metastatic disease.

The CD4 glycoprotein is the major cellular receptor for HIV. CD4 surface expression of monocytes decreases with time in culture while their susceptibility to HIV-1 increases. Our aim was to investigate whether this phenomenon occurs in macrophages that have differentiated in vivo by investigating CD4 expression and HIV-1 infection of human alveolar macrophages (AMs). Using flow cytometry to detect CD4 expression by Leu-3a labeled indirectly with fluorescein isothiocyanate or allophycocyanin, we found that CD4 was expressed at low but detectable levels, despite the high background autofluorescence well described in AMs. This finding was supported by the detection of CD4 mRNA in AMs using RT-PCR. T cell contamination of mRNA extracts of AMs was excluded by amplifying in parallel with primers to the constant region of the T cell receptor. Despite this low level of surface CD4, recombinant soluble CD4 and anti-CD4 antibody completely inhibited HIV-1 infection of AMs. We conclude that CD4, although expressed at low levels on the surface of AMs, appears to be critical to HIV-1 infection of these cells.

Hypobaric hypoxemia is experienced by passengers during commercial aircraft flight. In order to assess the extent of hypoxemia and to test whether hypobaric hypoxia can be accurately estimated at sea level, the results of the normobaric hypoxia altitude simulation test (N-HAST) were compared with those of the hypobaric hypoxia altitude simulation test (H-HAST) in six normal control subjects and nine patients with chronic airflow limitation (CAL) at simulated cabin altitudes of 6,000 ft (1,829 m) and both at rest and during exercise at 8,000 ft (2,438 m). Serial arterial blood samples were drawn during the breathing of 15.1 and 16.3% inspired oxygen at sea level (N-HAST) at rest and during light exercise, and during the breathing of room air at simulated cabin altitudes (H-HAST) of 609 mm Hg (6,000 ft) and 565 mm Hg (8,000 ft) at rest and during light exercise. As measured with the H-HAST technique, the mean (+/- SD) PaO2 of the normal group fell from 96.2 +/- 6.2 mm Hg (sea level) to 70.1 +/- 6.0 mm Hg (6,000 ft), and to 61.7 +/- 1.6 mm Hg (8,000 ft at rest) and 54.8 +/- 7.1 mm Hg (8,000 ft during exercise) (p < 0.005 by analysis of variance [ANOVA]). In the CAL group, the mean (+/- SD) PaO2 fell from 75.8 +/- 8.2 mm Hg (sea level) to 57.0 +/- 6.3 mm Hg (6,000 ft), and 49.5 +/- 6.1 mm Hg (8,000 ft at rest), and 38.6 +/- 7.5 mm Hg (8,000 ft during exercise) (p < 0.005 by ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)

Cytogenetic analysis has indicated that deletion of chromosome 9p occurs in a significant number of non-small cell lung and mesothelioma tumors. Using paired oligonucleotide primers, we have undertaken an extensive analysis of 9p markers to determine homozygous and heterozygous loss of marker sequences. Homozygous loss of D9S169 and D9S171, both of which map centromeric to the IFN gene cluster, were noted in three cell lines (27%) and hemizygous deletions of one or both of these loci was found in a further six cell lines (54%). These data suggest the presence of a potential tumor suppressor gene for lung cancer in proximity to D9S169 and D9S171 at 9p21.

In a case-control study of 71 consecutive new male cases of lung cancer and 71 male hospital control patients, previous dietary and alcohol intake, smoking pattern, occupation, dust exposure, and family history of lung cancer were investigated. The cases and controls were similar in age, country of origin, area of residence, and marital status. Using a frequency-based assessment of previous dietary intake, broad food groups were similar for cases and controls. Cases had a significantly lower intake of fish than controls did (odds ratio = 0.5, confidence interval = 0.2-1.0, p = 0.05). A protective effect for fish consumption in lung cancer has not been previously reported. The dietary intake of foods containing retinol and beta-carotene and the intake of alcohol were not significantly different between cases and controls. For cases, smoking duration was longer and the time since cessation for exsmokers was shorter, cigarette pack years were longer, and the number of cigarettes smoked per day was greater. The factors of occupation, dust exposure, and family history of cancer (including lung cancer) were similarly distributed between cases and controls.

The intratracheal administration of bleomycin in rats elicits an acute inflammatory response in the lung followed by the development of pulmonary fibrosis. The alveolar macrophage (AM) is a key effector cell involved in this process because of its potential to release a variety of hormonelike molecules (cytokines) that can modulate systemic responses as well as the local response of other lung cells including the interstitial fibroblast. In this report, we have documented the chronology of the in vitro spontaneous release of AM cytokines after a single instillation of bleomycin. We show that supernatants from AM harvested after the administration of bleomycin but not after saline contain lymphocyte-activating factor (interleukin-1) activity. Maximal activity was detected between 6 and 12 h and was barely detectable by Day 7 after bleomycin. In addition, supernatants showing interleukin-1 (IL-1) activity also inhibited the proliferation of log-phase normal rat lung fibroblasts. Fractionation of supernatants from AM harvested 6 h after bleomycin demonstrated that both lymphocyte-activating factor and fibroblast modulatory activity coelute in the same 18-kDa region, suggesting that IL-1 may demonstrate both activities. We also report here the spontaneous release of a second AM cytokine, hepatocyte-stimulating factor, which we have recently shown in humans to be identical to interferon beta 2 and which initiates the hepatic acute-phase protein response. The release of this 30-kDa cytokine from AM of rats exposed to bleomycin has a different chronology than does IL-1, showing a steady increase over time, with maximal activity at Day 28 after bleomycin.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary fibrosis results from an altered deposition of collagen within the lung parenchyma. This alteration is likely the result of both increased fibroblast proliferation and abnormalities in fibroblast collagen metabolism. Although the development of pulmonary fibrosis is preceded by inflammatory events in the lung, it is unclear whether altered fibroblast behavior requires continuous exposure to inflammatory mediators or alternatively results from the emergence in the lung of fibroblast populations possessing characteristics such as to explain the abnormalities seen in pulmonary fibrosis. To examine the latter hypothesis, we have established a number of fibroblast cell lines from control (C) lung tissue as well as from tissue from patients with active pulmonary fibrosis (PF), and have examined their in vitro proliferative characteristics. Our data show that PF fibroblasts proliferate significantly faster compared to C fibroblasts under standard culture conditions. We have also examined the in vitro proliferative characteristics of a substantial number of clonally derived fibroblasts. We report that a marked heterogeneity exists in terms of proliferation and also that a small but significant number of fast-growing clones are present in panels of clones derived from fibrotic tissue. These data suggest that there exists in fibrotic tissue, clones of fibroblasts with intrinsic growth characteristics which could in itself explain the increased fibroblast proliferation seen in pulmonary fibrosis. The fibrotic clones may emerge as dominant in the fibrotic lung under conditions of injury and repair likely to favor the expansion of this phenotype.

The rate of absorption across the alveolar-capillary membrane of inhaled 99mTc-DTPA and the concentration of albumin in the bronchoalveolar lavage (BAL) fluid were characterized in a rat model of bleomycin-induced pulmonary fibrosis. Adult male Lewis rats were studied from 1 h to 120 days after a single intratracheal instillation of bleomycin (0.5 to 0.6 U/100 g body weight). The retention of 99mTc-DTPA in the lungs, expressed as a percentage of the baseline radioactivity, was determined at 15 min (%R15) after delivery of the tracer. The %R15 was 83.7 +/- 6.0 for normal untreated rats and 84.3 +/- 3.7 for saline-treated animals. The rate of absorption of 99mTc-DTPA began to increase 24 h after bleomycin, reaching a maximum at Day 7, with %R15 = 56.0 +/- 6.5 (p less than 0.0001). Resolution to control values occurred by Day 34 after bleomycin. At Day 45 after bleomycin, the rate of absorption of 99mTc-DTPA was slower than sham (control), with %R15 = 89.2 +/- 1.9 (p less than 0.5). However, from Day 63 onwards, removal was not different from control. The concentration of albumin in the BAL fluid began to increase 48 h after bleomycin, was 10-fold greater than control by Day 7 (150 +/- 38 versus 16 +/- 3 micrograms/ml), and returned to control values by Day 28. The percentage of neutrophils in the BAL increased at 12 h, reached a plateau of 33 +/- 9% between 4 and 7 days, and then returned to control values by Day 14.(ABSTRACT TRUNCATED AT 250 WORDS)