Polarimetric Thomson scattering measurements in Joint European Torus high temperature plasmas.

Thomson scattered light is polarized in the same orientation as the incident laser beam at low electron temperatures (Te). At high Te, part of the spectrum begins to become randomly polarized due to relativistic reasons. First measurements of the depolarized Thomson scattering spectrum were obtained from Joint European Torus (JET) pulses in 2016. This paper builds upon these initial measurements with the data obtained during 2021. These new measurements improve upon first results, in particular, by obtaining spectral measurements of the depolarized spectrum. The recent JET campaign was well suited to these measurements with long and hot plasmas. The resulting data are averaged over many plasmas and laser pulses to obtain a measurement of the amount of "p" and "s" scattered light as a function of Te. This experimentally obtained d(p/s)/dTe is then fitted and found to show reasonable agreement with the theoretically predicted depolarized fraction. Error estimates on the measured "p/s" have been obtained and show that the measurements are meaningful. This is good news for ITER for which the intention is to use this measurement as a check on Te determined by the core plasma Thomson scattering diagnostic by using conventional spectral measurement techniques.

Ambient habitat noise and vibration at the Georgia Aquarium.

Underwater and in-air noise evaluations were completed in performance pool systems at Georgia Aquarium under normal operating conditions and with performance sound tracks playing. Ambient sound pressure levels at in-pool locations, with corresponding vibration measures from life support system (LSS) pumps, were measured in operating configurations, from shut down to full operation. Results indicate noise levels in the low frequency ranges below 100 Hz were the highest produced by the LSS relative to species hearing thresholds. The LSS had an acoustic impact of about 10 dB at frequencies up to 700 Hz, with a 20 dB re 1 µPa impact above 1000 Hz.

First divertor Thomson scattering measurements on MAST-U.

MAST-U is equipped with a Super-X divertor, which aims to reduce heat flux to the target and promote detachment. Measurements of plasma electron density and temperature in the Super-X chamber offer insight into the processes at work in this type of divertor. First data have been obtained from the MAST-U divertor Thomson scattering diagnostic designed to measure these quantities. Following a Raman scattering calibration in nitrogen, the diagnostic operated over a number of plasma pulses in the first physics campaign. Electron density and temperature measurements have been taken in attached and detached conditions as the strike leg moved through the field of view of the diagnostic. The system operated with a dedicated 30 Hz laser with timing synchronized to seven similar lasers installed in the core Thomson system. Electron densities in the range of 1 × 1018-5 × 1019 m-3 have been measured by the system throughout these regimes. Although the system was specified to measure from 1 to 40 eV, electron temperatures in the Super-X divertor in the first campaign were low, and measurement down to 0.5 eV has been critical, particularly close to the detachment front. This generation of polychromator has been designed with increased stray light rejection compared to those used in the core system. This has proved successful with very low levels of stray light observed.

Low temperature Thomson scattering on MAST-U.

A new divertor Thomson scattering system has been developed for the MAST-U tokamak. The diagnostic will produce electron density and temperature profiles along the Super-X strike leg. The existing polychromator design has been adapted for low temperature measurements. A new 1061 nm channel with 2 nm bandwidth has been added to enable measurements down below the previous ∼5 eV limit on the core system. The optical filters used in the system have OD6 light rejection alongside a 1064.1 nm laser line filter to reduce stray light in the digitized channels. A new averaging technique has been applied to the scattered signal traces to improve the core Thomson data in the scrape-off layer. The technique reduces the systematic noise level in this region. This leads to a reduction in the error values for electron density and temperature measurements and, in particular, the digitizer noise. The technique has been applied to produce a radial profile for a number of L-mode MAST discharges down to very low densities of ∼1 × 1018 m-3.

Bleomycin-induced pulmonary fibrosis in hamsters. An alveolar macrophage product increases fibroblast prostaglandin E2 and cyclic adenosine monophosphate and suppresses fibroblast proliferation and collagen production.

Bleomycin-induced pulmonary fibrosis in hamsters is associated with collagen accumulation that results from increased lung collagen synthesis rates. However, 1-2 wk after intratracheal instillation of bleomycin, lung collagen synthesis rates decline toward control values. To evaluate the potential role of the bronchoalveolar macrophage in regulating lung collagen production, we studied the effects of macrophages from normal and bleomycin-treated hamsters upon fibroblasts in vitro. We observed: (a) Medium from macrophage cultures decreased fibroblast [3H]thymidine incorporation and nondialyzable [3H]hydroxyproline production in a dose-dependent manner. Fibroblast cell counts were decreased in exposed cultures, and fibroblast viability was unchanged. Procollagen prolyl hydroxylation and prolyl-transfer RNA-specific activity were not altered by macrophage medium; this indicates that [3H]hydroxyproline reflects collagen production rate under the experimental conditions. (b) The suppressive effect of macrophage medium was selective for collagen since collagen production decreased more than noncollagen protein production. (c) Medium from bleomycin-treated hamster macrophages suppressed fibroblast proliferation and collagen production to a greater degree than medium from normal hamster macrophages. (d) Fibroblast suppression by macrophage medium was associated with increased fibroblast endogenous prostaglandin E2 production and intracellular cyclic AMP (cAMP). (e) Incubation of fibroblasts with indomethacin before exposure completely inhibited prostaglandin E2 production and increases in cAMP, and eliminated suppression of fibroblast proliferation and collagen production. The macrophage-derived suppressive factor has an apparent molecular weight of 20,000-30,000 and is heat stable. It does not appear to be species restricted since both hamster and human lung fibroblasts are similarly suppressed. It is at least in part preformed in macrophages obtained by lavage, but its production can also be stimulated in vitro. We concluded that alveolar macrophages release a product that stimulates endogenous fibroblast prostaglandin E2 production and cAMP formation with resultant suppression of fibroblast proliferation and collagen production. Enhanced release of suppressive factor by macrophages during a time when lung collagen production is declining in bleomycin-induced pulmonary fibrosis suggests that macrophages may limit collagen accumulation in pulmonary fibrosis.

Effects of interferon-gamma on expression of cell surface receptors for collagen and deposition of newly synthesized collagen by cultured human lung fibroblasts.

We used cultured human diploid lung fibroblasts as a model system to examine the effects of recombinant IFN-gamma on synthesis of collagen, matrix deposition of newly synthesized collagen, and the expression of cell surface receptors for collagen. Using [3H]proline-labeled cells we found that IFN-gamma resulted in dose-dependent inhibition of fibroblast collagen synthesis. Pulse-chase experiments to analyze compartmentalization of newly synthesized collagen showed that the decrease in collagen synthesis was confined to the soluble pool of procollagen in the medium, while extracellular matrix associated collagen was not changed, indicating that a larger proportion of newly synthesized collagen was deposited into the matrix in IFN-gamma exposed fibroblasts (34.2 vs. 25.3%). This increase in the efficiency of collagen matrix deposition was associated with enhanced expression of a cell surface receptor for collagen as detected by indirect immunofluorescence labeling and analysis by flow cytometry. Fibroblasts (IMR-90) cultured in the presence of IFN-gamma (1,000 U/ml) exhibited a twofold increase in mean linear fluorescence intensity compared with cells cultured under control conditions. The distribution of log fluorescence intensity in both control and IFN-gamma exposed cells was normally distributed about the mean, indicating that discrete subpopulations with respect to receptor expression were not present. Increased fluorescence intensity and log normal distribution of fluorescence intensity also were identified in IFN-gamma-treated lung fibroblasts from a normal adult individual and two strains obtained from patients with pulmonary fibrosis. These results indicate that IFN-gamma modulates fibroblast collagen matrix deposition as well as collagen synthesis. The associated increase in collagen receptors suggests that cytokine-mediated modulation of the cell surface maybe a contributing factor in regulation of fibroblast collagen accumulation in the extracellular matrix or in cellular interaction with collagen-containing matrix. Such an effect could modulate the interaction of fibroblasts with extracellular matrix at sites of inflammation and play an important role in the remodeling of matrix during repair from tissue injury.

Bleomycin-induced synthesis of type I procollagen by human lung and skin fibroblasts in culture.

Bleomycin is a chemotherapeutic agent sometimes associated with pulmonary fibrosis and skin lesions in patients undergoing treatment. We examined the mechanisms of increased collagen deposition on bleomycin-induced fibrosis by incubating human lung and skin fibroblast cultures with [14C]proline; the synthesis of [14C]hydroxyproline relative to DNA or cell protein was taken as an index of procollagen formation. Procollagen synthesis by lung cells in the presence of 0.1 and 1.0 microgram/ml bleomycin was significantly increased and similar results were obtained with skin fibroblasts. The relative synthesis of genetically distinct types of collagen was measured by isolating the newly synthesized type I and type III procollagens by DEAE-cellulose chromatography. The proportion of type III procollagen of total newly synthesized procollagen in control lung fibroblast cultures was 17.4 +/0 0.6% (mean +/- S.E.) while the corresponding value in cells incubated in 1 microgram/ml bleomycin was 12.5 +/- 0.6% (n = 6, P < 0.01). Similar results were obtained when the ratios of newly synthesized type I and type III collagens were estimated by interrupted polyacrylamide disc gel electrophoresis in sodium dodecyl sulfate after a limited proteolytic digestion with pepsin. The results indicate that the increased procollagen synthesis induced by bleomycin in fibroblast cultures is predominantly directed towards the synthesis of type I procollagen.

Pulmonary function testing prior to hematopoietic stem cell transplantation.

The pretransplant pulmonary function test plays an important role in the management of noninfectious pulmonary complications after hematopoietic stem cell transplantation (HCT). Although these tests are widely used as standard preoperative assessments in the nontransplant population, common conditions associated with the HCT patient requires that particular attention be given to interpretation of pulmonary function testing (PFT) results, such as comparison of serial pulmonary function tests and evaluation of the diffusion capacity. Although their utility in helping to predict the likelihood of developing post transplant pulmonary complications and mortality is not well established, current data indicate that pretransplant PFTs are important as a reference for the interpretation of post transplant PFTs and for identifying patients at high risk for developing pulmonary complications and/or mortality after HCT. Future studies of pretransplant pulmonary function should consider the advances in HCT, so that pretransplant PFTs will become a useful tool in pretransplant risk assessment and help the transplant oncologist to determine the most appropriate conditioning regimen for a patient with compromised lung function.

In situ histochemical detection of beta-galactosidase activity in lung: assessment of X-Gal reagent in distinguishing lacZ gene expression and endogenous beta-galactosidase activity.

Bacterial lacZ is one of the most commonly used reporter genes for assessing gene transfer to lung. However, lung contains endogenous beta-galactosidase (beta-Gal), which can confound estimation of exogenous lacZ expression by histochemical techniques (i.e., X-Gal) for in situ demonstration of enzyme activity. We investigated several parameters of the X-Gal reaction, including time and temperature of X-Gal exposure as well as lung tissue processing and fixation techniques, and found that none of these could be used to distinguish between endogenous and exogenous beta-Gal activities. The mammalian and bacterial beta-Gal enzymes, however, have pH optima in the acidic and neutral ranges, respectively. Exposing whole lung, lung minces, or mounted frozen sections of lung to X-Gal at mildly alkaline pH (pH 8.0-8.5), minimized detection of endogenous activity in lungs from a variety of species while preserving that resulting from bacterial enzyme activity in a transgenic mouse expressing lacZ. This technique was also useful in distinguishing endogenous activity from that resulting from adenovirus-mediated lacZ gene transfer to diploid lung fibroblasts in primary culture. An appropriate buffer that maintains the desired pH throughout the duration of X-Gal exposure must be used.

Perflubron enhances adenovirus-mediated gene expression in lungs of transgenic mice with chronic alveolar filling.

Perfluorochemical (PFC) liquids have both low surface tension and a high capacity to dissolve O2 and CO2, and have been shown to improve gas exchange and lung compliance in animal models of lung injury. We have previously demonstrated that perflubron and other PFC liquids enhance transgene expression in lungs of spontaneously breathing normal rodents after intratracheal instillation of either adenoviral or liposomal vectors followed by a single instillation of PFC liquid. We reasoned that PFC liquids may also be useful for enhancing transgene expression in abnormal lungs. GM-CSF knockout mice develop chronic accumulation of surfactant lipids and proteinaceous material in alveolar spaces and serve as a useful model of chronic alveolar filling. Intratracheal instillation of the adenoviral vector Adlac-Z resulted in patchy in situ distribution of beta-Gal activity, predominantly in larger proximal airways. In contrast, in mice instilled with Adlac-Z followed by instillation of a single dose of perflubron (10 ml/kg body weight), increased expression was observed in distal airway and alveolar epithelial cells. In particular, expression was observed in epithelial cells of debris-filled alveoli. Spectrophotometric measure of quantitative beta-Gal activity in lung homogenates demonstrated increased activity in lungs of mice receiving Adlac-Z plus perflubron compared with lungs of animals receiving Adlac-Z alone. These studies demonstrate that use of perflubron enhances transgene expression in lungs of animals with a chronic alveolar filling process. This approach may be applicable for gene delivery in diseases marked by chronic airway or alveolar filling such as cystic fibrosis.

Ultraviolet radiation-induced connective tissue changes in the skin of hairless mice.

Hairless mice (Skh/ hr1 ) were exposed to ultraviolet A (UVA; peak irradiance at 365 nm), or to ultraviolet B (UVB; peak irradiance at 313 nm) radiation. The animals received 12 treatments on alternate days. Connective tissue changes in the skin were monitored by assaying hydroxyproline and desmosine as an indication of collagen and elastin concentrations, respectively. The activities of prolyl hydroxylase and collagen glucosyl-transferase, enzymes participating in the biosynthesis of collagen, were also assayed. The concentration of elastin was significantly increased in mice treated with UVA or UVB. The concentration of collagen was unaffected by the treatments, but the activity of prolyl hydroxylase, reflecting collagen synthetic capacity, was decreased in UVA-treated mice. The collagen glucosyl-transferase activity was unchanged. Irradiation of purified human prolyl hydroxylase with UVA in vitro decreased the enzyme activity at higher doses, but UVB had no effect. The results indicate that definitive changes in the biochemistry of dermal connective tissues can be induced by exposure of mice to UV irradiation.

Biopsy diagnosis and clinical outcome of persistent focal pulmonary lesions after marrow transplantation.

We reviewed the results of all percutaneous fine needle aspirations (FNA) and open lung biopsies (OLB) after bone marrow transplantation at our center (1984-1987) for the evaluation of focal lung lesions that developed or persisted despite antibiotic administration. We sought to determine the prevalence and types of infections, the yield of diagnostic procedures, and the clinical outcome of these focal lesions. Infection was documented in 78% (18/23) of all lesions and was fungal in each case. FNA detected fungal lung infection with a sensitivity of 67% (10/15) but had a negative predictive value of only 50% (5/10). Complications occurred in 15% of FNA. OLB without prior FNA was performed in 6 cases and demonstrated fungal infections in 5. Overall, seven of the 18 patients with localized invasive fungal lung disease recovered after antifungal therapy. This study demonstrates that focal lung lesions that develop or persist despite antibiotics after BMT are most often fungal. FNA may safely identify these localized infections in selected patients and with appropriate treatment recovery may be achieved.

Pulmonary venoocclusive disease following bone marrow transplantation.

We report two cases of pulmonary venoocclusive disease (PVOD) in children with acute lymphoblastic leukemia treated by marrow allograft transplantation following conditioning with high-dose 1-3 bis chloroethyl-1 nitrosourea (BCNU), etoposide (VP-16), and cyclophosphamide (Cy). Both patients developed symptomatic pulmonary hypertension documented by right heart catheterization. Open-lung biopsy of one patient demonstrated PVOD evident even on frozen sections stained with hematoxylin and eosin. High-dose methylprednisolone was associated with significant clinical improvement in both patients. Pulmonary symptoms resolved in one patient who subsequently died in leukemic relapse. PVOD resolved in the other patient, only to recur when steroids were discontinued and then again respond to reinstitution of therapy. More aggressive therapy for malignant diseases may increase the incidence of PVOD. Prompt recognition of its subtle clinical and histological manifestations allows early institution of steroid therapy, which may be beneficial.

Neutralization of tumor necrosis factor-alpha action delays but does not prevent lung injury induced by alloreactive T helper 1 cells.

BACKGROUND: Lung injury occurs frequently after allogeneic bone marrow transplantation in association with graft-versus-host disease, an immune response that involves both cellular and cytokine components. In a murine model, we recently showed that cloned alloreactive T helper (Th)1 cells can cause lung injury associated with increased production of tumor necrosis factor (TNF)-alpha by alveolar macrophages (J Immunol 1998; 161: 1913). METHODS: To evaluate the role of TNF-alpha in this model, we injected in vitro-activated Th1 cells into the following: (1) recipients deficient in receptors for TNF; (2) C57BL/6 control mice; (3) C57BL/6 mice, pretreated with soluble TNFRIIFc (a dimorphic high-affinity TNF antagonist); (4) mice expressing TNFRIIFc transgene under control of the surfactant apoprotein C promoter (SPCTNFRIIFc); and (5) wild-type littermate controls (C57BL/6) (n=3-6 mice/group). RESULTS: At 1 and 3 days after i.v. Th1 cell transfer, recipients were killed for analysis of lung histology, bronchoalveolar lavage (BAL) protein, and BAL cell counts. Control mice (wild type) at day 1 after injection had a mild to moderate mononuclear perivasculitis and increased interstitial cellularity. At day 3, lesions were more severe and perivasculitis also involved larger veins. TNFR-deficient mice had normal lung or minimal lung inflammation at day 1. At day 3, perivasculitis of medium-sized vessels was present, but there was no apparent involvement of larger veins. Results in mice treated with soluble TNFRIIFc and transgenic mice (SPCsTNFRIIFc) were similar to controls. BAL protein and BAL cell counts did not differ between any of the experimental groups. CONCLUSIONS: We conclude that lung inflammation induced by Th1 cells may be only delayed when TNF-alpha action is blocked. The persistence of abnormalities indicates that other proinflammatory pathways are involved in injury caused by these cells.

Pulmonary cavitation and massive hemoptysis caused by an unsuspected intraparenchymal foreign body.

A patient presented with massive hemoptysis, and a chest roentgenogram revealed a right lower lobe cavity which contained a movable mass of soft tissue density. He had sustained a gunshot wound to the chest seven years earlier. Thoracotomy was performed for uncontrollable hemoptysis, and parenchymal cavitation was found which contained a plastic foreign body. We retrieved a film following the original injury which revealed a mass density that proved to be a plastic wadding capsule from a shotgun shell. This type of complication from intraparenchymal foreign bodies is discussed and the unusual roentgenographic presentation of this patient is considered.

Open lung biopsy diagnosis of diffuse pulmonary infiltrates after marrow transplantation.

The results were reviewed of 111 open lung biopsies (OLB) performed on 109 marrow transplantation recipients with diffuse pulmonary infiltrates between January 1983 and July 1987. We determined the frequency and types of infections identified, and the relationship to time after transplantation. Infection was found in 70 of the 111 cases (63 percent) and cytomegalovirus (CMV) was present in 90 percent of all cases with infection. Infection was identified in only five of 26 (19 percent) cases within the first 30 days after transplant, and when present, was viral. The prevalence of infection after 30 days (over 75 percent of 85 cases) was significantly higher (chi 2 = 26.2, p = 0.00001). Bacterial or yeast infections were found in only four cases (4 percent) (two cases each), and Pneumocystis carinii in six cases (6 percent). Simultaneous infection with two or more organisms was found in four cases (4 percent). Four of 25 autopsies performed within ten days after OLB revealed fungal infections with Aspergillus not detected at OLB. Thus, the prevalence of infection detected by OLB is low within the first 30 days after marrow transplantation among patients receiving broad spectrum antibiotics. CMV infection is found in most transplantation recipients who undergo OLB with diffuse infiltrates between days 30 and 180.

Complications of fiberoptic bronchoscopy in thrombocytopenic patients.

STUDY OBJECTIVE: To determine the risk of epistaxis and pulmonary hemorrhage due to fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) in the presence of thrombocytopenia. DESIGN: Prospective study of all patients undergoing FOB with BAL with a 4.9-mm-diameter bronchoscope after bone marrow transplantation (BMT) during a 6-month period. SETTING: A single BMT center. PATIENTS: Forty-seven BMT recipients undergoing 66 FOB with BAL. Thrombocytopenia (platelets < 100,000/ml) was present in 58 (88 percent). Platelets were < 50,000/ml in 44 (67 percent) and < 20,000/ml in 13 (20 percent). In the thrombocytopenic patients, FOB with BAL was transnasal in 37 (64 percent), transoral in 5 (9 percent), and via endotracheal tube in 16 (28 percent). INTERVENTIONS: Fiberoptic bronchoscopy with BAL using a bronchoscope (Pentax FB-15H) (4.9-mm diameter). In one case, a pediatric bronchoscope (Pentax FB-10H; 3.5-mm diameter) was used in a 7-year-old patient. MEASUREMENTS AND RESULTS: The BAL was diagnostic in 22 of 47 patients studied (47 percent). Complications occurred in 7 of 58 (12 percent) thrombocytopenic patients (epistaxis and/or hemoptysis, 4; bradycardia, 2; bronchospasm, 1) of which all but 1 were minor and self-limiting. One life-threatening complication of severe epistaxis occurred during a transoral FOB in a patient with prior epistaxis (platelet count, 18,000/ml). One of 8 (13 percent) nonthrombocytopenic patients had hemoptysis. No patient had worsening fever or oxygenation at 4 h and no patient displayed worsening radiographic infiltrates suggestive of pulmonary hemorrhage attributable to the BAL at 24 h. CONCLUSIONS: We conclude that transnasal FOB in thrombocytopenic patients was safe, being associated with minor airway bleeding in 3 of 37 patients (8 percent). In conclusion, FOB with BAL, even via the transnasal route, may be performed with relative safety despite the presence of significant thrombocytopenia.

Implications of early airflow decline after myeloablative allogeneic stem cell transplantation.

The clinical significance of early airflow decline after myeloablative allogeneic hematopoietic SCT is uncertain. We performed a retrospective cohort analysis to determine if airflow decline by day 100 is associated with later development of transplant-related airflow obstruction (AFO) and increased mortality risk. Overall, 750 (40%) patients had airflow decline by day 100. Development of airflow decline by day 100 was associated with an increased risk for AFO at 1 year (relative risk 2.6, 95% confidence interval 2.1-3.1) but not with an increase in mortality risk (hazard ratio (HR) 0.86, P=0.05). However, patients with the fastest rate of decline between day 100 and 1 year (12.5% per year +/-24) had the highest mortality risk (HR 3.2, P<0.001). In conclusion, airflow measurements made on day 100 do not predict the rate of airflow decline between day 100 and 1 year, and therefore are not useful as a single measurement for determining mortality risk associated with development of AFO. Closer monitoring of the rate of airflow decline during the first year may facilitate the timely detection and treatment of early airflow decline and prevent the development of fixed AFO and increased mortality risk after hematopoietic stem cell transplant.

Incidence, risk factors, and mortality from pneumonia developing late after hematopoietic stem cell transplantation.

The incidence, etiology, outcome, and risk factors for developing pneumonia late after hematopoietic stem cell transplantation (SCT) were investigated in 1359 patients transplanted in Seattle. A total of 341 patients (25% of the cohort) developed at least one pneumonic episode. No microbial or tissue diagnosis (ie clinical pneumonia) was established in 197 patients (58% of first pneumonia cases). Among the remaining 144 patients, established etiologies included 33 viral (10%), 31 bacterial (9%), 25 idiopathic pneumonia syndrome (IPS, 7%), 20 multiple organisms (6%), 19 fungal (6%), and 16 Pneumocystis carinii pneumonia (PCP) (5%). The overall cumulative incidence of first pneumonia at 4 years after discharge home was 31%. The cumulative incidences of pneumonia according to donor type at 1 and 4 years after discharge home were 13 and 18% (autologous/syngeneic), 22 and 34% (HLA-matched related), and 26 and 39% (mismatched related/unrelated), respectively. Multivariate analysis of factors associated with development of late pneumonia after allografting were increasing patient age (RR 0.5 for <20 years, 1.2 for >40 years, P=0.009), donor HLA-mismatch (RR 1.6 for unrelated/mismatched related, P=0.01), and chronic graft-versus-host disease (GVHD; RR 1.5, P=0.007). Our data suggest that extension of PCP prophylaxis may be beneficial in high-risk autograft recipients. Further study of long-term anti-infective prophylaxis based on patient risk factors after SCT appear warranted.

Bronchiolitis associated with bone marrow transplantation.

New onset airflow obstruction after BMT is a relatively common complication and may be seen in as many as 11% of long-term survivors of allogeneic BMT with chronic GVHD. Bronchiolitis and, occasionally, obliterative bronchiolitis is seen in the majority of cases in which histopathology is available. The primary risk factors recognized are the presence of clinical chronic GVHD, administration of methotrexate as an immunosuppressive, and older recipient age. Improved control of chronic GVHD with effective agents such as cyclosporine likely will decrease the incidence of this airway disorder. The causes probably are multifactorial and donor cytotoxic T-lymphocyte interaction with host cells is a likely contributor in many cases. The clinical course is variable, but the process usually is fatal in cases with rapidly progressive or severe obstruction. Interventions are directed at immune suppression and at diagnosing and treating infections that frequently occur in association with the airflow obstruction.