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PubMed1987

Comparative O2-. responses of lung macrophages and blood phagocytic cells in the rat. Possible relevance to IgA immune complex induced lung injury.

IgA immune complex-induced lung injury in the rat is oxygen radical mediated and partially complement-dependent but develops fully after neutrophil depletion. The extent to which monocytes, lung interstitial macrophages, and alveolar macrophages may be involved in the development of lung injury in this model is unclear. To further understand the pathogenesis of IgA lung injury, we have examined the capacity of phagocytic cells isolated from different anatomic compartments of the lung to produce toxic oxygen-derived metabolites. [3H]Thymidine pulse labeling and autoradiography as well as in vivo phagocytosis studies were used to distinguish macrophages isolated from the alveolar and interstitial compartments. Lung interstitial macrophages were characterized ultrastructurally, cytochemically, and functionally. Interstitial macrophages were relatively uniform in size, had blunt pseudopodia, and contained almost no intracytoplasmic lamellar inclusions compared to alveolar macrophages. Similar to monocytes and alveolar macrophages, interstitial macrophages contained nonspecific esterase activity and exhibited the capacity to phagocytize latex and opsonized zymosan particles. Lung interstitial and alveolar macrophages incubated with IgA immune complexes, IgG immune complexes, or phorbol ester (PMA) produced similar amounts of O2-. in a dose-dependent manner. In contrast, peripheral blood neutrophils responded to IgG immune complexes and PMA but not to IgA immune complexes. Monocytes produced a small amount of O2-. in response to PMA but almost no O2-. in response to IgA or IgG immune complexes. These data are consistent with recent in vivo studies which indicate that IgA immune complex lung injury is neutrophil independent. The data provide direct in vitro evidence that lung interstitial and alveolar macrophages produce O2-. following incubation with PMA, IgA, or IgG immune complexes and may therefore contribute to the development of oxygen radical mediated lung injury.

Animals↗

PubMed1988

Limiting-dilution analysis of T cells extracted from solid human lung tissue: comparison of precursor frequencies for proliferative responses and lymphokine production between lung and blood T cells from individual donors.

This study evaluates the frequency and functions of immunocompetent T cells at the clonal level in solid human lung tissue versus peripheral blood. Enzymatic digestion of slices of histologically normal human lung yielded 18-42 x 10(6) viable mononuclear cells per gram wet weight tissue, of which 60-72% were lymphocytes; based upon these recoveries and the known weight of adult lung, the (median) lung parenchymal lymphocyte population can be estimated as 6 x 10(9), being of the same order as the blood pool and 15-30-fold that recoverable by broncho-alveolar lavage. Flow cytometric analysis indicated that the bulk of these lymphocytes was OKT3+/T11+ (CD3/CD2) T cells. Purified blood and lung T cells from each subject were cultured at limiting dilution in the presence of PHA, irradiated feeder cells and recombinant human IL-2. The mean frequency estimates for PHA-responsive T cells in these populations were 1 in 1.23 (81%) and 1 in 3.22 (31%) for blood and lung, respectively. This difference was seen for T cells from each donor and was highly significant by paired t-test (P less than 0.002). Analysis of surface phenotypes and functions of individual blood and T-cell clones indicated comparable frequencies for OKT4 (CD4) and OKT8 (CD8) expression, TNF production and mitogen-induced cytotoxicity. However, a striking inverse relationship was observed between the overall frequency of IL-2-producing clones (79% for blood versus 47% for lung) and interferon-gamma (IFN-gamma)-producing clones (46% versus 87%). These differences were found for each subject, and both were highly significant (P less than 0.001) by paired t-test. The available literature suggests that the majority of these lung T cells represent transient immigrants derived from the blood. Accordingly, the functional differences we have observed suggest either selective trapping within the lung vascular bed of peripheral blood T cells of certain functional phenotypes or alternatively selection/modulation of T cells by lung-derived factors during their transit through the tissue.

Adult↗

PubMed1980

Diagnosis, stage, and prognosis of lung carcinoma by preoperative assay of lung tumor antigen-sensitive T lymphocytes.

Levels of circulating T lymphocytes sensitized to human lung tumor--associated antigens (LTA) were determined by the antigen-stimulated active rosette-forming T cell (AgARFC) assay. These levels were correlated with detection, pathological tumor stage, and postassay survival of patients with lung carcinoma. Peripheral blood lymphocytes (PBLs), from patients found to have lung cancer, were incubated with LTA and produced increased AgARFC compared to PBLs incubated without LTA. Significant levels of LTA-sensitive T cells were found in preoperative PBLs of 80% of patients with Stage I disease (8/10, p < 0.0005), 60% of those with Stage II disease (3/5, p < 0.025), and 46% of those with Stage III primary lung cancer (12/26, p < 0.01), compared with 11% of patients with either benign lung lesions (2/12) or lung metastases (0/6) of nonpulmonary malignant tumors (by chi square analysis). Postoperative survival correlated significantly with preoperative levels of LTA-sensitive T cells by AgARFC assay within Stage I lung cancer (r = 0.807, p < 0.0005). Stage I + II (r = 0.689, p < 0.001), and Stage III (r = 0.657, p < 0.001, not treated with chemotherapy). Preoperative PBL from patients with Stage I + II lung cancer were more frequently sensitized to LTA in the AgARFC assay than from patients with nonpulmonary carcinomas (0/22) or cigarette smokers (1/7) without pulmonary lesions (p < 0.0005). These findings demonstrate a high rate of detection of early, resectable lung carcinomas by preoperative AgARFC assay of PBL sensitized to LTA, and a significant correlation of LTA-sensitive T cell levels with tumor stage and patient survival. The AgARFC assay may be of prognostic as well as diagnostic value in the evaluation of patients with lung carcinoma.

Antigens, Neoplasm↗

PubMed1993

Postoperative pulmonary tissue changes following autogenous lung and artificial lung bypass. Comparative studies.

With regard to pulmonary tissue damage secondary to extracorporeal circulation, most studies focused on the pulmonary histological changes after artificial lung bypass, but none compared the pre- and post-operative pulmonary changes of artificial lung with those of autogenous lung. We compared the changes in autogenous lung oxygenation and artificial lung oxygenation during cardiopulmonary bypass (CPB). The results showed that autogenous lung oxygenation is less injurious to the lung than bubble oxygenation and is more physiological. We think that during open heart surgery with autogenous lung bypass, the lung is functioning physiologically and supplied with normal amount of oxygen, while using bubble oxygenation for CPB, the native lung, the only nonperfused organ, is insulted by pulmonary ischemia, which is one of the most important reasons for pulmonary injury after CPB.

Animals↗

PubMed1993

Lung injury produced by moderate lung overinflation in rats.

In models using both intact animals and isolated lungs of rats, rabbits, lambs, and dogs, application of high airway pressure and resultant lung overdistension has been shown to cause lung injury. Under pathological conditions, the more normal portions of the lung may be subjected to relative overdistension when supranormal airway pressures are used. A small animal model of lung overdistension is presented here to demonstrate that lung injury can be caused by moderate lung overdistension. Rats were anesthetized with Ketamine and pentobarbital. A tracheostomy was performed and arterial and central venous catheters placed. The animal was placed in a plethysmograph and an infant ventilator was used to provide mechanical ventilation. In the first experiment, animals in group A (n = 6, control) were ventilated at tidal volume (TV) of 5 mL/kg for 5 hours. Animals in group B (n = 6) were ventilated at TV 15 mL/kg for 60 minutes and then were returned TV of 5 mL/kg for the remainder of the experiment. Animals in group C (n = 5) were ventilated at TV 20 mL/kg for 60 minutes and then returned to TV 5 mL/kg. Static lung compliance and arterial blood gasses were measured. Wet and dry lung weight were obtained after sacrifice. In the second experiment, animals in group D (n = 4, control) were ventilated at TV 5 mL/kg for 240 minutes and killed. Animals in group E (n = 4) were ventilated at TV 20 mL/kg for 60 minutes, returned to TV 5 mL/kg, and killed at 240 minutes. Fluorescein-labeled albumin was administered to each animal prior to mechanical ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2005

Impact of intensity-modulated radiation therapy as a boost treatment on the lung-dose distributions for non-small-cell lung cancer.

PURPOSE: To investigate the feasibility of intensity-modulated radiotherapy (IMRT) as a method of boost radiotherapy after the initial irradiation by the conventional anterior/posterior opposed beams for centrally located non-small-cell lung cancer through the evaluation of dose distributions according to the various boost methods. METHODS AND MATERIALS: Seven patients with T3 or T4 lung cancer and mediastinal node enlargement who previously received radiotherapy were studied. All patients underwent virtual simulation retrospectively with the previous treatment planning computed tomograms. Initial radiotherapy plans were designed to deliver 40 Gy to the primary tumor and involved nodal regions with the conventional anterior/posterior opposed beams. Two radiation dose levels, 24 and 30 Gy, were used for the boost radiotherapy plans, and four different boost methods (a three-dimensional conformal radiotherapy [3DCRT], five-, seven-, and nine-beam IMRT) were applied to each dose level. The goals of the boost plans were to deliver the prescribed radiation dose to 95% of the planning target volume (PTV) and minimize the volumes of the normal lungs and spinal cord irradiated above their tolerance doses. Dose distributions in the PTVs and lungs, according to the four types of boost plans, were compared in the boost and sum plans, respectively. RESULTS: The percentage of lung volumes irradiated >20 Gy (V20) was reduced significantly in the IMRT boost plans compared with the 3DCRT boost plans at the 24- and 30-Gy dose levels (p = 0.007 and 0.0315 respectively). Mean lung doses according to the boost methods were not different in the 24- and 30-Gy boost plans. The conformity indexes (CI) of the IMRT boost plans were lower than those of the 3DCRT plans in the 24- and 30-Gy plans (p = 0.001 in both). For the sum plans, there was no difference of the dose distributions in the PTVs and lungs according to the boost methods. CONCLUSIONS: In the boost plans the V20s and CIs were reduced significantly by the IMRT plans, but in the sum plans the effects of IMRT on the dose distributions in the tumor and lungs, like CI and V20, were offset. Therefore, to keep the beneficial effect of IMRT in radiotherapy for lung cancer, it would be better to use IMRT as a whole treatment plan rather than as a boost treatment.

Aged↗

PubMed1998

Acute and chronic effects of bilateral lung transplantation without cardiopulmonary bypass on the first transplanted lung.

BACKGROUND: Bilateral lung transplantation (BLT) without cardiopulmonary bypass (CPB) may exacerbate reperfusion injury to the initially engrafted lung because of increases in pulmonary flow during implantation of the second graft. METHODS: In a retrospective review of 23 BLT patients, we hypothesized that BLT without CPB injures the first transplanted lung measured by acute and late graft dysfunction compared to the second transplanted lung. Of the 23 BLT, 19 underwent transplantation without CPB while 4 patients were placed on CPB secondary to hemodynamic instability. RESULTS: Acute graft function was assessed by radiographic scoring of lung quadrants (blinded radiologist; 0 = no infiltrate; 1 = infiltrate; maximum = 2 per lung) and by arterial/alveolar oxygen tension ratios (PaO2/ FiO2) ratios. Late graft function was evaluated by quantitative perfusion scan. Lung perfusion was graded as abnormal if less than 50% on the right or less than 45% on the left (Fisher's exact). Radiographic scores were not different between first and second implanted lungs at 1 and 24 hours, PaO2/FiO2 ratios at 1 and 24 hours were 273+/-26 and 312+/-23, respectively, and perfusion scans at 3 and 12 months revealed normal differential blood flow. CONCLUSIONS: These findings suggest no acute or chronic differences occur between the first or second transplanted lung completed without CPB.

Adult↗

PubMed2002

Optimizing radiation treatment plans for lung cancer using lung perfusion information.

PURPOSE: To study the impact of incorporation of lung perfusion information in the optimization of radical radiotherapy (RT) treatment plans for patients with medically inoperable non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The treatment plans for a virtual phantom and for five NSCLC patients with typical defects of pre-RT lung perfusion were optimized to minimize geometrically determined parameters as the mean lung dose (MLD), the lung volume receiving more than 20 Gy (V20), and the functional equivalent of the MLD, using perfusion-weighted dose-volume histograms. For the patients the (perfusion-weighted) optimized plans were compared to the clinically applied treatment plans. RESULTS: The feasibility of perfusion-weighted optimization was demonstrated in the phantom. Using perfusion information resulted in an increase of the weights of those beams that were directed through the hypo-perfused lung regions both for the phantom and for the studied patients. The automatically optimized dose distributions were improved with respect to lung toxicity compared with the clinical treatment plans. For patients with one hypo-perfused hemi-thorax, the estimated gain in post-RT lung perfusion was 6% of the prescribed dose compared to the geometrically optimized plan. For patients with smaller perfusion defects, perfusion-weighted optimization resulted in the same plan as the geometrically optimized plan. CONCLUSION: Perfusion-weighted optimization resulted in clinically well applicable treatment plans, which cause less radiation damage to functioning lung for patients with large perfusion defects.

Carcinoma, Non-Small-Cell Lung↗

PubMed2003

Lung transplantation. Lung preservation.

Over the past decade, improvements in the technique of lung preservation have led to significant reduction in the incidence of ischemia-reperfusion-induced lung injury after lung transplantation. The challenge remains to improve the number of donor lungs available for transplantation. While the number of patients on the waiting list is constantly increasing, only 10% to 30% of donor lungs are currently being used for transplantation. Hence, the development of new strategies to assess, repair, and improve the quality of the lungs could have a tremendous impact on the number of transplants performed. In addition, an improved understanding of the mechanisms involved in lung preservation might help elucidate the potential link between acute lung injury and chronic graft dysfunction. In the future, genetic analysis using novel technologies such as microarray analysis will help researchers determine which genes control the injury seen in the transplantation process. Hopefully, this information will provide new insights into the mechanisms of injury and reveal potential new strategies and targets for therapies to improve lung preservation.

Graft Rejection↗

PubMed2001

Expression and regulation of hemeoxygenase 1 in healthy human lung and interstitial lung disorders.

Hemeoxygenase 1 (HO-1) has been implicated in the protection of lung tissue against exogenous oxidant exposure. However, the expression and cellular distribution of HO-1 in human lung continue to be poorly characterized. The localization of HO-1 was studied in histopathologically healthy lung from nonsmoking patients with a carcinoid or other lung tumor (5 cases), pulmonary sarcoidosis (13 cases), and chronic interstitial pneumonias (9 cases, usual interstitial pneumonia; 10 cases, desquamative interstitial pneumonia). Immunostaining was graded from 0 (no immunoreactivity) to +++ (intense immunoreactivity). In healthy lung, HO-1 was localized to alveolar macrophages with reactivity varying from moderate to intense, and in bronchial epithelium, alveolar epithelium, endothelium, and interstitium, the immunoreactivity was not detectable or was very low. Sarcoidosis and interstitial pneumonias showed intense HO-1 immunoreactivity in alveolar macrophages in most of the cases and weak to intense immunoreactivity in the granulomas of sarcoidosis. The immunoreactivity of interstitium was negative or weak in the fibrotic areas of the lung and also in the samples of bronchoalveolar lavage fluid obtained from the patients with UIP. Western blotting indicated that HO-1 is up-regulated by exposure of monocytes to formylated peptide, fMLP, which causes respiratory burst in the cells, and that inhibition of HO-1 by tin protoporphyrin potentiates the injury of fMLP-exposed cells. In conclusion, these data show differential distribution of HO-1 in human lung cells and strongly suggest the importance of HO-1, especially in the defense of alveolar macrophages in normal human lung and in the inflammatory, but not in the fibrotic, stage of interstitial lung disorders.

Blotting, Western↗

PubMed1985

Quantification of asymmetric lung pathophysiology as a guide to the use of simultaneous independent lung ventilation in posttraumatic and septic adult respiratory distress syndrome.

The management of impaired respiratory gas exchange in patients with nonuniform posttraumatic and septic adult respiratory distress syndrome (ARDS) contains its own therapeutic paradox, since the need for volume-controlled ventilation and PEEP in the lung with the most reduced compliance increases pulmonary barotrauma to the better lung. A computer-based system has been developed by which respiratory pressure-flow-volume relations and gas exchange characteristics can be obtained and respiratory dynamic and static compliance curves computed and displayed for each lung, as a means of evaluating the effectiveness of ventilation therapy in ARDS. Using these techniques, eight patients with asymmetrical posttraumatic or septic ARDS, or both, have been managed using simultaneous independent lung ventilation (SILV). The computer assessment technique allows quantification of the nonuniform ARDS pattern between the two lungs. This enabled SILV to be utilized using two synchronized servo-ventilators at different pressure-flow-volumes, inspiratory/expiratory ratios, and PEEP settings to optimize the ventilatory volumes and gas exchange of each lung, without inducing excess barotrauma in the better lung. In the patients with nonuniform ARDS, conventional ventilation was not effective in reducing shunt (QS/QT) or in permitting a lower FIO2 to be used for maintenance of an acceptable PaO2. SILV reduced per cent v-a shunt and permitted a higher PaO2 at lower FIO2. Also, there was x-ray evidence of ARDS improvement in the poorer lung. While the ultimate outcome was largely dependent on the patient's injury and the adequacy of the septic host defense, by utilizing the SILV technique to match the quantitative aspects of respiratory dysfunction in each lung at specific times in the clinical course, it was possible to optimize gas exchange, to reduce barotrauma, and often to reverse apparently fixed ARDS changes. In some instances, this type of physiologically directed ventilatory therapy appeared to contribute to a successful recovery.

Adolescent↗

PubMed1988

Transbronchial lung biopsy for the diagnosis of rejection in heart-lung transplant patients.

Long-term success of human lung transplantation has been hindered by the lack of an effective and repeatable method of obtained tissue from the transplanted lung for histology. Management of patients is complicated by the difficulty in distinguishing clinically between opportunistic infection of the lung and rejection. As a result, a large number of patients in recent reports develop chronic disabling obliterative bronchiolitis, believed to be the consequence of "chronic" rejection. Twenty-one patients have undergone heart-lung transplantation in our institute since 1984. During fiberoptic bronchoscopy, 43 transbronchial lung biopsies were performed in 15 patients. Twenty episodes of rejection occurred in 11 patients, from whom 16 sets of biopsies showed the typical changes of perivascular infiltrate and mucosal inflammation. Three biopsies were falsely negative; six routine biopsies performed when patients were well were all normal. Overall sensitivity was 84% and specificity 100%. By contrast, the sensitivity of the chest radiograph was only 40%. Opportunistic lung infection in 8 patients was diagnosed by transbronchial biopsy with a sensitivity of 38% and specificity of 100%. In no patient with opportunistic infection were the histologic features of rejection seen. Transbronchial lung biopsy offers a safe and repeatable method to obtain tissue from heart-lung transplants for histology. It has enabled the management of the lung transplant patient to be equivalent to that of the kidney, liver, and heart transplant patient.

Biopsy↗

PubMed2006

Morphometric examination of native lungs in human lung allograft recipients.

The aim of the study was to estimate the degree of lung damage in patients with alpha(1)-antitrypsin (alpha1AT) deficiency, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) at the time of lung transplantation. Using unbiased stereological methods, lung-, bronchial- and vessel-volume, capillary length, and alveolar surface area and densities were estimated in recipient lungs from 21 consecutive patients with pre-transplant diagnoses including COPD (n=7), alpha1AT deficiency (n=6) and CF (n=8). Six unused adult donor lungs served as controls. Information relating to patient demography and pre-transplant lung function was obtained by retrospective chart review. Disease groups differed significantly with respect to demographics and pre-transplant lung function. Total lung volume was similar in all groups. Bronchial volume was significantly larger in CF patients compared to the control group (p<0.0001) and to the other two diagnostic groups: alpha1AT deficiency (p=0.0001) and COPD (p<0.0001). Alveolar surface density and capillary length density were significantly lower in patients with alpha1AT deficiency and COPD compared to controls (p<0.0001, respectively) and to patients with CF (p<0.0002, respectively). There were no correlations between clinical lung function and morphometric measurements. We conclude that unbiased microscopic stereological morphometry is an evolving science with the potential to elucidate pulmonary disease pathogenesis.

Adult↗

PubMed1998

Incidental lung carcinoma detected at CT in patients selected for lung volume reduction surgery to treat severe pulmonary emphysema.

PURPOSE: The authors present their experience with previously unsuspected carcinoma of the lung detected at preoperative computed tomography (CT) in patients with severe pulmonary emphysema who were scheduled to undergo lung volume reduction surgery. MATERIALS AND METHODS: Preoperative chest CT was performed in 148 patients (84 men, 64 women; mean age, 65 years +/- 8 [standard deviation]) with advanced pulmonary emphysema before lung volume reduction surgery. At surgery, an attempt was made to excise any pulmonary nodule considered suspicious for carcinoma at CT. RESULTS: Eighteen pulmonary nodules suspicious for lung cancer were found at CT in 17 (11%) of the 148 patients. Sixteen of these 148 nodules were resected at lung volume reduction surgery. Nine non-small cell carcinomas (adenocarcinoma, n = 4, including three with bronchioloalveolar differentiation; poorly differentiated, n = 3; squamous cell carcinoma, n = 2) were found in eight (5%) patients. Eight of the cancers were stage I, and one was unstaged surgically. Maximum diameters of the cancers ranged between 1.0 and 3.8 cm (median, 1.6 cm). The seven (5%) other resected nodules were all benign. CONCLUSION: A 5% rate of stage I primary lung cancer in patients selected for lung volume reduction surgery suggests that performance of chest CT in candidates for lung volume reduction surgery is appropriate not only to identify patterns of pulmonary parenchymal destruction but also to search for stage I lung cancer.

Adenocarcinoma↗

PubMed2001

Complications (excluding hyperinflation) involving the native lung after single-lung transplantation: incidence, radiologic features, and clinical importance.

PURPOSE: To determine the incidence, importance, and radiologic features of native lung complications after single-lung transplantation. MATERIALS AND METHODS: Seventeen (15%) of 111 single-lung transplant recipients developed native lung complications (excluding hyperinflation) 0-58 months (mean, 17 months) after transplantation. Complaints at presentation, culture or histopathologic results, diagnostic or therapeutic procedures, and outcome were recorded. Chest radiographs (n = 17) and computed tomographic (CT) scans (n = 8) obtained at time of diagnosis were reviewed. Serial radiographs were assessed for disease progression or improvement. RESULTS: The most common complications were infection (n = 10), caused by bacteria (n = 4), fungi (n = 4), or mycobacteria (n = 2), typically manifested as lobar or segmental opacities on chest radiographs or CT scans. Lung cancer manifested as a solitary well-circumscribed nodule (n = 1), multiple nodules (n = 1), or a hilar mass (n = 1). Five (29%) of 17 patients died of native lung complications. Seven patients underwent mediastinoscopy (n = 3), lobectomy (n = 2), thoracoscopic wedge resection (n = 2), tube thoracostomy (n = 2), or pneumonectomy (n = 1) for diagnosis or treatment. CONCLUSION: Native lung complications occurred in 17 (15%) single-lung transplant recipients, were most commonly due to infection or lung cancer, and caused serious morbidity or mortality in 12 (71%) of 17 patients affected.

Adult↗

PubMed1979

Effect of lung surface tension on bronchial collapsibility in excised dog lungs.

Bronchial collapsibilities were studied in air- and saline-filled excised dog lungs. The intrapulmonary bronchi were isolated from the rest of the lung parenchyma with beads placed at their tributary bronchi as described previously by Takishima et al. (J. Appl. Physiol. 38: 875-881, 1975). Pressure-volume relations of the isolated bronchi were obtained while lung volume (VL) was kept constant. When lung recoil pressure (PL) was reduced by filling the lung with saline at a given VL, bronchial areas were smaller and bronchial collapsibilities were larger than in the air-filled lung. When bronchial areas and bronchial collapsibilities in air- and saline-filled lungs were compared at a given PL, they were approximately identical. We concluded that bronchial areas and collapsibilities were primarily determined by PL rather than VL, and lung surface tension itself made bronchial collapsibility equal to or even less than the degree of collapsibility due to forces applied from surrounding lung tissues that distended the bronchi.

Airway Resistance↗

PubMed2006

Transpulmonary pressures and lung mechanics with glossopharyngeal insufflation and exsufflation beyond normal lung volumes in competitive breath-hold divers.

Throughout life, most mammals breathe between maximal and minimal lung volumes determined by respiratory mechanics and muscle strength. In contrast, competitive breath-hold divers exceed these limits when they employ glossopharyngeal insufflation (GI) before a dive to increase lung gas volume (providing additional oxygen and intrapulmonary gas to prevent dangerous chest compression at depths recently greater than 100 m) and glossopharyngeal exsufflation (GE) during descent to draw air from compressed lungs into the pharynx for middle ear pressure equalization. To explore the mechanical effects of these maneuvers on the respiratory system, we measured lung volumes by helium dilution with spirometry and computed tomography and estimated transpulmonary pressures using an esophageal balloon after GI and GE in four competitive breath-hold divers. Maximal lung volume was increased after GI by 0.13-2.84 liters, resulting in volumes 1.5-7.9 SD above predicted values. The amount of gas in the lungs after GI increased by 0.59-4.16 liters, largely due to elevated intrapulmonary pressures of 52-109 cmH(2)O. The transpulmonary pressures increased after GI to values ranging from 43 to 80 cmH(2)O, 1.6-2.9 times the expected values at total lung capacity. After GE, lung volumes were reduced by 0.09-0.44 liters, and the corresponding transpulmonary pressures decreased to -15 to -31 cmH(2)O, suggesting closure of intrapulmonary airways. We conclude that the lungs of some healthy individuals are able to withstand repeated inflation to transpulmonary pressures far greater than those to which they would normally be exposed.

Adult↗

PubMed1995

Alterations of lung and chest wall mechanics in patients with acute lung injury: effects of positive end-expiratory pressure.

In 16 mechanically ventilated patients with acute lung injury (ALI) (eight patients with moderate ALI [moderate group], eight patients with severe ALI [adult respiratory distress syndrome, ARDS group]) and in eight normal anesthetized-paralyzed subjects (control group), we partitioned the total respiratory system mechanics into the lung (L) and chest wall (w) mechanics using the esophageal balloon technique together with the airway occlusion technique during constant flow inflation. We measured lung elastance (Est,L), chest wall elastance (Est,w), and total lung (Rmax, L) and chest wall (Rmax,w) resistance. Rmax,L includes airway (Rmin,L) and "additional" lung resistance (DR,L). DR,L represents the "additional" component due to the viscoelastic phenomena of the lung tissues and time-constant inequalities (pendelluft). Measurements were repeated at 0, 5, and 10 cm H2O of positive end-expiratory pressure (PEEP) in the control group and at 0, 5, 10, and 15 cm H2O PEEP in patients with ALI. The end-expiratory lung volume (EELV) was measured at each level of PEEP. Specific total lung (sRmax,L), airway (sRmin,L), and "additional" lung (sDR,L) resistances were obtained as Rmax,L x EELV, Rmin,L x EELV, and DR,L x EELV, respectively. At PEEP 0 cm H2O, we found that both Est,L (23.7 +/- 5.5 and 13.8 +/- 3.3 versus 9.3 +/- 1.7 cm H2O/L; p < 0.01) and Est,w (13.2 +/- 5.4 and 9.9 +/- 2.1 versus 5.6 +/- 2.3 cm H2O/L; p < 0.01) were markedly increased in patients with ARDS and moderate ALI compared with control subjects, with a significant (p < 0.01) effect of the severity of the disease on Est,L (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗