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Methods BT10+ was an international, multicentre, follow-up study of participants who were previously enrolled in the AIR, RISA, and AIR2 trials and who had 10 or more years of follow-up since bronchial thermoplasty treatment. Data on patient demographics, quality of life, lung function, CT scans (AIR2 participants only), severe exacerbations, and health-care use during the previous year were collected at the BT10+ 10-year outcomes study visit. The primary effectiveness endpoint was durability of the thermoplasty treatment effect, determined by comparing the proportion of participants who had severe exacerbations during the first and fifth years after bronchial thermoplasty treatment with the proportion of participants who had severe exacerbations during the 12-month period before the BT10+ visit. The primary safety endpoint was the absence of clinically significant post-treatment respiratory image changes after bronchial thermoplasty, defined as bronchiectasis or bronchial stenosis as confirmed by pulmonary volumetric highresolution CT scan at the BT10+ visit (AIR2 participants only). All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT03243292. The last patient was enrolled on Dec 11, 2018. The last patient completed follow-up on Jan 10, 2019.Findings The BT10+ study enrolled 192 (45%) of the 429 participants who were enrolled in the AIR, RISA, and AIR2 trials. The BT10+ participants comprised 136 who received bronchial thermoplasty (52% of the 260 participants who received bronchial thermoplasty in the original trials), and 56 sham or control participants (33% of 169 from the original trials). 18 (32%) sham or control participants received bronchial thermoplasty after the previous trials concluded. The participants included in BT10+ were followed for 10?8?15?6 years (median 12?1 years) post-treatment. Baseline characteristics were similar between participants enrolled in BT10+ and those not enrolled. Participants treated with bronchial thermoplasty had similar proportions of severe exacerbations at the BT10+ visit (34 [25%] of 136 participants) compared with 1 year (33 [24%] of 135 participants; difference 0?6%, 95% CI ?9?7 to 10?8) and 5 years (28 [22%] of 130 participants; difference 3?5%, ?6?7% to 13?6) after treatment. Quality of life measurements and spirometry were similar between year 1, year 5, and the BT10+ visit. At the BT10+ study visit, pulmonary high-resolution CT scans from AIR2 participants treated with bronchial thermoplasty showed that 13 (13%) of 97 participants had bronchiectasis. When compared with baseline high-resolution CT scans, six (7%) of 89 participants treated with bronchial thermoplasty who did not have bronchiectasis at baseline had developed bronchiectasis after treatment (5 classified as mild, 1 classified as moderate). Participants treated with bronchial thermoplasty after the original study and participants in the sham or control group also had reductions in severe exacerbations at the BT10+ visit compared with baseline.Summary Background Bronchial thermoplasty is an endoscopic treatment for uncontrolled asthma. Previous randomised clinical trials have shown that bronchial thermoplasty reduces severe exacerbations in people with asthma. However, the long-term efficacy and safety of bronchial thermoplasty beyond 5 years is unknown. The BT10+ study aimed to investigate the efficacy and safety of bronchial thermoplasty after 10 or more years of follow-up. Methods BT10+ was an international, multicentre, follow-up study of participants who were previously enrolled in the AIR, RISA, and AIR2 trials and who had 10 or more years of follow-up since bronchial thermoplasty treatment. Data on patient demographics, quality of life, lung function, CT scans (AIR2 participants only), severe exacerbations, and health-care use during the previous year were collected at the BT10+ 10-year outcomes study visit. The primary effectiveness endpoint was durability of the thermoplasty treatment effect, determined by comparing the proportion of participants who had severe exacerbations during the first and fifth years after bronchial thermoplasty treatment with the proportion of participants who had severe exacerbations during the 12-month period before the BT10+ visit. The primary safety endpoint was the absence of clinically significant post-treatment respiratory image changes after bronchial thermoplasty, defined as bronchiectasis or bronchial stenosis as confirmed by pulmonary volumetric high resolution CT scan at the BT10+ visit (AIR2 participants only). All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT03243292. The last patient was enrolled on Dec 11, 2018. The last patient completed follow-up on Jan 10, 2019. Findings The BT10+ study enrolled 192 (45%) of the 429 participants who were enrolled in the AIR, RISA, and AIR2 trials. The BT10+ participants comprised 136 who received bronchial thermoplasty (52% of the 260 participants who received bronchial thermoplasty in the original trials), and 56 sham or control participants (33% of 169 from the original trials). 18 (32%) sham or control participants received bronchial thermoplasty after the previous trials concluded. The participants included in BT10+ were followed for 10middot8-15middot6 years (median 12middot1 years) post-treatment. Baseline characteristics were similar between participants enrolled in BT10+ and those not enrolled. Participants treated with bronchial thermoplasty had similar proportions of severe exacerbations at the BT10+ visit (34 [25%] of 136 participants) compared with 1 year (33 [24%] of 135 participants; difference 0middot6%, 95% CI -9middot7 to 10middot8) and 5 years (28 [22%] of 130 participants; difference 3middot5%, -6middot7% to 13middot6) after treatment. Quality of life measurements and spirometry were similar between year 1, year 5, and the BT10+ visit. At the BT10+ study visit, pulmonary high-resolution CT scans from AIR2 participants treated with bronchial thermoplasty showed that 13 (13%) of 97 participants had bronchiectasis. When compared with baseline high-resolution CT scans, six (7%) of 89 participants treated with bronchial thermoplasty who did not have bronchiectasis at baseline had developed bronchiectasis after treatment (5 classified as mild, 1 classified as moderate). Participants treated with bronchial thermoplasty after the original study and participants in the sham or control group also had reductions in severe exacerbations at the BT10+ visit compared with baseline.Interpretation Our findings suggest that efficacy of bronchial thermoplasty is sustained for 10 years or more, with an acceptable safety profile. Therefore, bronchial thermoplasty is a long-acting therapeutic option for patients with asthma that remains uncontrolled despite optimised medical treatment. Funding Boston Scientific. Copyright (c) 2021 Elsevier Ltd. All rights reserved.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a major limitation in the long-term survival of lung transplant recipients (LTRs). However, the risk factors in the development of BOS remain undetermined. We conducted an international cohort study of LTRs to assess whether Aspergillus colonization with large or small conidia is a risk factor for the development of BOS.METHODS: Consecutive LTRs from January 2005 to December 2008 were evaluated. Rates of BOS and associated risk factors were recorded at 4 years. International Society of Heart and Lung Transplantation criteria were used to define fungal and other infections. A Cox proportional-hazards-model was constructed to assess the association between Aspergillus colonization and the development of BOS controlling for confounders.RESULTS: A total of 747 LTRs were included. The cumulative incidence of BOS at 4 years after transplant was 33% (250 of 747). Additionally, 22% of LTRs experienced Aspergillus colonization after transplantation. Aspergillus colonization with either large (hazard ratio [HR] = 0.6, 95% confidence interval [CI] = 0.3-1.2, p = 0.12) or small conidia (HR = 0.9, 95% CI = 0.6-1.4, p = 0.74) was not associated with the development of BOS. Factors associated with increased risk of development of BOS were the male gender (HR = 1.4, 95% CI = 1.1-1.8, p = 0.02) and episodes of acute rejection (1-2 episodes, HR = 1.5, 95% CI = 1.1-2.1, p = 0.014; 3-4 episodes, HR = 1.6, 95% CI = 1.0-2.6, p = 0.036; >4 episodes, HR = 2.2, 95% CI = 1.1-4.3, p = 0.02), whereas tacrolimus use was associated with reduced risk of BOS (HR = 0.6, 95% CI = 0.5-0.9, p = 0.007).CONCLUSIONS: We conclude from this large multicenter cohort of lung transplant patients, that Aspergillus colonization with large or small conidia did not show an association with the development of BOS.

Organ transplantation is a significant risk factor for the development of skin cancer. The impact of skin type, immunosuppressive regimens, and photosensitizing agents requires further study. The objective of this study was to compare skin cancer development between Caucasian and non-Caucasian transplant recipients at the University of Southern California. We performed a retrospective chart review of lung and liver transplantations to determine the incidence of post-transplant skin cancer. Participants included patients who underwent lung or liver transplantation between 2005 and 2013 at our institution. Patients included in the study were limited to those who survived through the study observation period. We analyzed 475 patients who underwent transplantation, including 370 liver transplant recipients and 105 lung transplant recipients. Among these, 46.3% identified as Caucasian, while 53.7% were non-Caucasian. Over a mean follow-up of 7.9 years, 11.8% of Caucasian patients developed at least one skin cancer, compared with 2.7% of non-Caucasians (p

BACKGROUND: Invasive aspergillosis (IA) is a frequent complication in lung transplant recipients (LTRs). Clinical risk factors for IA have not been fully characterized, especially in the era of extensive anti-fungal prophylaxis. The primary objective of this study was to evaluate the clinical risk factors associated with IA in LTRs. The secondary objective was to assess the mortality in LTRs who had at least 1 episode of IA compared with LTRs who never had experienced IA.METHODS: We conducted an international, multicenter, retrospective cohort study of 900 consecutive adults who received lung transplants between 2005 and 2008 with 4years of follow-up. Risk factors associated with IA were identified using univariate and multiple regression Cox proportional hazards models.RESULTS: Anti-fungal prophylaxis was administered to 61.7% (555 of 900) of patients, and 79 patients developed 115 episodes of IA. The rate to development of the first episode was 29.6 per 1,000 person-years. Aspergillus fumigatus was the most common species isolated (63% [72 of 115 episodes]). Through multivariate analysis, significant risk factors identified for IA development were single lung transplant (hazard ratio, 1.84; 95% confidence interval, 1.09-3.10; p = 0.02,) and colonization with Aspergillus at 1 year post-transplantation (hazard ratio, 2.11; 95% confidence interval, 1.28-3.49; p = 0.003,). Cystic fibrosis, pre-transplant colonization with Aspergillus spp, and use of anti-fungal prophylaxis were not significantly associated with the development of IA. Time-dependent analysis showed IA was associated with higher mortality rates.CONCLUSION: Incidence of IA remains high in LTRs. Single-lung transplant and airway colonization with Aspergillus spp. within 1 year post-transplant were significantly associated with IA.

Background Bronchial thermoplasty (BT) is a non-pharmacologic, endoscopic treatment for asthma not well controlled with long-acting b-agonists and inhaled corticosteroids. Long-term efficacy and safety of BT beyond 5 years is unknown. The BT10+ study was designed to evaluate the efficacy and safety of BT at 10+ years follow-up. Methods BT10+ is an international, multi-center, ≥10yrs follow-up study on subjects who were enrolled in the AIR, RISA and AIR2 BT trials. Demographics, quality of life, lung function, severe exacerbations (SE, defined as asthma exacerbations requiring systemic corticosteroids) and healthcare utilisation for the previous year were collected at the BT10+ study visit. Additionally, AIR2 subjects who received a pulmonary high-resolution CT (HRCT) at baseline had a second scan at the BT10+ study visit to determine if clinically relevant changes, such as bronchiectasis, occur after BT. Results Of 429 subjects enrolled AIR, RISA, and AIR2, 192 were followed-up at 10.6–15.8 years (12.1 median) post-treatment at 16 centers; of these, 136 were treated with BT and 38 were control/sham subjects in previous studies. Baseline characteristics between subjects enrolled and not enrolled in BT10+ did not show meaningful differences. For BT subjects, no increases in the rate of hospitalisations or ER visits were observed compared to baseline and rates of SE were stable compared to Year 1 (figure 1). While both groups experienced fewer SE after treatment, BT subjects had fewer SE than control/sham subjects at the BT10+ visit; this was not significant. Quality of life (AQLQ, ACQ) and spirometry results were comparable between Years 1, 5, and 10+ for both groups. Pulmonary HRCT scans from AIR2 subjects at the BT10+ study visit showed 9.5% (2/21) of control/sham subjects and 13.4% (13/97) of BT subjects had bronchiectasis; however, when these were compared with baseline HRCT scans, only 5.3% (5/94) of BT subjects had developed bronchiectasis after their baseline visit. Conclusion The BT10+ study suggests that efficacy of BT is sustained over 10 years and that BT has an acceptable safety profile.

Background: BT is an endoscopic treatment for uncontrolled asthma. The long-term efficacy and safety of BT beyond 5 years is not known. Objective: To evaluate the efficacy and safety of BT at 10+ years follow-up. Methods: BT10+ is an international, multi-center, ≥10yrs follow-up study on subjects who were previously enrolled in the AIR, RISA and AIR2 trials. Demographics, quality of life, lung function, severe exacerbations (SE, defined as exacerbations requiring systemic corticosteroids) and healthcare utilisation for the previous year were collected. Results: Of the 429 subjects enrolled in the previous studies, 192 subjects had a follow-up at 10.6-15.8 years (12.1 median) post-treatment at 16 centers: 137 treated with BT during a previous study, 18 control/sham treated with BT post-study, and 37 control/sham only. Rates for hospitalisations, emergency visits and SE for BT subjects from the year prior to BT to the year prior to the BT 10+ visit are shown in Figure 1. No increases in hospitalisations or ER visits were observed compared to baseline and SE were stable compared to Year 1. No deterioration in rates were shown for control/sham only and post-study BT patients. Quality of life and spirometry results were comparable between Years 1, 5, and 10+ for all groups. Conclusion: The BT10+ study suggests that efficacy of bronchial thermoplasty is sustained over 10 years. Funding: Boston Scientific

This study evaluated the independent contribution of voriconazole to the development of squamous cell carcinoma (SCC) in lung transplant recipients, by attempting to account for important confounding factors, particularly immunosuppression. This international, multicenter, retrospective, cohort study included adult patients who underwent lung transplantation during 2005-2008. Cox regression analysis was used to assess the effects of voriconazole and other azoles, analyzed as time-dependent variables, on the risk of developing biopsy-confirmed SCC. Nine hundred lung transplant recipients were included. Median follow-up time from transplantation to end of follow-up was 3.51 years. In a Cox regression model, exposure to voriconazole alone (adjusted hazard ratio 2.39, 95% confidence interval 1.31-4.37) and exposure to voriconazole and other azole(s) (adjusted hazard ratio 3.45, 95% confidence interval 1.07-11.06) were associated with SCC compared with those unexposed after controlling for important confounders including immunosuppressants. Exposure to voriconazole was associated with increased risk of SCC of the skin in lung transplant recipients. Residual confounding could not be ruled out because of the use of proxy variables to control for some confounders. Benefits of voriconazole use when prescribed to lung transplant recipients should be carefully weighed versus the potential risk of SCC. EU PAS registration number: EUPAS5269.

Background Previously, we and other investigators have described reversible loss of lung elastic recoil in patients with acute and persistent, moderate-to-severe, chronic, treated asthma who never smoked, and its adverse effect on maximal expiratory airflow. In four consecutive autopsies, we reported the pathophysiologic mechanism(s) has been unsuspected mild, diffuse, middle and upper lobe centrilobular emphysema. Methods We performed prospective studies (5 to 22 years) in 25 patients (12 female) with chronic asthma, age 55 ± 15 years, who never smoked, with persistent moderate-to-severe expiratory obstruction. Studies included measuring blood eosinophils, IgE, total exhaled nitric oxide (NO), central airway NO flux, peripheral airway/alveolar NO concentration, impulse oscillometry, heliox curves, lung elastic recoil, and high-resolution thin-section (1 mm) lung CT imaging at full inspiration with voxel quantification. Results In 25 patients with stable asthma with varying type 2 phenotype, after 270 μg of aerosolized albuterol sulfate had been administered with a metered dose inhaler with space chamber, FVC was 3.1 ± 1.0 L (83% ± 13% predicted) (mean ± SD), FEV 1 was 1.8 ± 0.6 L (59% ± 11%), the FEV 1 /FVC ratio was 59% ± 10%, and the ratio of single-breath diffusing capacity of the lung for carbon monoxide to alveolar volume was 4.8 ± 1.1 mL/min/mm Hg/L (120% ± 26%). All 25 patients with asthma had loss of static lung elastic recoil pressure, which contributed equally to decreased intrinsic airway conductance in limiting expiratory airflow. Lung CT scanning detected none or mild emphysema. In all four autopsied asthmatic lungs previously reported and one unreported explanted lung, microscopy revealed unsuspected mild, diffuse centrilobular emphysema in the upper and middle lung fields, and asthma-related remodeling in airways. In eight cases, during asthma remission, there were increases in measured static lung elastic recoil pressure-calculated intrinsic airway conductance, and measured maximal expiratory airflow at effort-independent lung volumes. Conclusions As documented now in five cases, unsuspected microscopic mild centrilobular emphysema is the sentinel cause of loss of lung elastic recoil. This contributes significantly to expiratory airflow obstruction in never-smoking patients with asthma, with normal diffusing capacity and near-normal lung CT scan results. Trial Registry Protocol No. 20070934 and Study No. 1090472, Western Institutional Review Board, Olympia, WA; ClinicalTrials.gov; No. NCT00576069; URL: www.clinicaltrials.gov.

Background We examined the relationship between voriconazole utilization and non-melanoma skin cancer (NMSC) development among adult lung and heart/lung transplant patients who were continuously enrolled in a large U.S. commercial health plan. Methods Cox proportional hazards regression models were constructed to assess both the crude and adjusted effect of voriconazole usage on NMSC development. Overall, 467 adult lung (98%) and heart/lung (2%) transplant patients (60% male) with median age of 58 years were analyzed. Results Fifty-seven (12%) patients developed NMSC over a median follow-up time of 610 days. At the crude level, patients with any (vs. none) claim for voriconazole were more likely to develop NMSC (19% vs. 12%, hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.02, 2.96, P = 0.04). However, after statistical adjustment for demographic and clinical factors, the effect was largely diminished and no longer statistically significant (HR: 1.23, 95% CI: 0.71, 2.14, P = 0.45). Results were similar when modeling average and total dose of voriconazole. Risk factors significantly related to NMSC development were being male, older age, sun exposure, history of chronic obstructive pulmonary disorder, and history of immune disorder. Conclusion Results suggest that the relationship between voriconazole utilization and NMSC among lung transplant patients may be a result of confounding by indication, and that controlling for underlying patient characteristics is paramount.

Background The estimated prevalence of hepatitis C virus (HCV) infection among lung transplant (LT) recipients is 1.9%. Many thoracic transplant programs are reluctant to transplant HCV-seropositive patients due to concerns of hepatic dysfunction caused by immunosuppression. The aims of this study are to survey current practices of US LT programs regarding HCV-seropositive patients and using the Organ Procurement and Transplantation Network/United Network for Organ Sharing database and to assess the clinical outcomes of HCV-positive compared with HCV-negative LT recipients. Methods A survey of US transplant centers that have performed more than 100 LTs was conducted. In addition, 170 HCV-seropositive and 9259 HCV-seronegative recipients who received HCV-seronegative donor organs between January 1, 2000, to December 31, 2007, were identified from the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Outcome variables including patient survival were compared between the two groups. Results A total of 64.4% centers responded to the survey. Ten of 29 (34.5%) programs would not consider HCV-seropositive patients for LT. Among the 19 programs that will consider HCV-seropositive patients, only five centers would transplant actively viremic patients. Overall patient survival rates of HCV-seropositive patients were similar to HCV-seronegative patients (84.7% at 1 year, 63.9% at 3 years, 49.4% at 5 years for HCV-seropositive group vs. 82.0% at 1 year, 65.0% at 3 years, 51.4% at 5 years for HCV-seronegative group, P=0.712). Relative risk of recipients for death remained statistically insignificant after adjusting for recipient age, donor age, obesity, sensitization, serum creatinine, and medical condition at time of transplant (relative risk [RR]=1.07 [0.84-1.38], P=0.581). Conclusions Since 2000, patient survival rates of HCV-positive patients are identical to those who are HCV-negative. However, most of these HCV-seropositive patients were probably nonviremic.

Background Neutrophilic corticosteroid-resistant asthma accounts for a significant proportion of asthma; however, little is known about the mechanisms that underlie the pathogenesis of the disease. Objective We sought to address the role of autophagy in lung inflammation and the pathogenesis of corticosteroid-resistant neutrophilic asthma. Methods We developed CD11c-specific autophagy-related gene 5 (Atg5) −/− mice and used several murine models to investigate the role of autophagy in asthmatic patients. Results For the first time, we found that deletion of the Atg5 gene specifically in CD11c + cells, which leads to impairment of the autophagy pathway, causes unprovoked spontaneous airway hyperreactivity and severe neutrophilic lung inflammation in mice. We found that severe lung inflammation impairs the autophagy pathway, particularly in pulmonary CD11c + cells in wild-type mice. We further found that adoptive transfer of Atg5 −/− , but not wild-type, bone marrow–derived dendritic cells augments lung inflammation with increased IL-17A levels in the lungs. Our data indicate that neutrophilic asthma in Atg5 −/− mice is glucocorticoid resistant and IL-17A dependent. Conclusion Our results suggest that lack of autophagy in pulmonary CD11c + cells induces neutrophilic airway inflammation and hyperreactivity.

Activin A, a homodimeric protein (βAβA) and a member of the TGF-β superfamily, is involved in the inflammatory repair process. Using cDNA microarray analysis, we discovered strong induction of the activin βA gene in human mast cells (MC) on stimulation with PMA and calcium ionophore (A23187). Activin βA mRNA was also highly induced in primary cultured murine bone marrow MC (BMMC) after stimulation by IgE receptor cross-linking. Secretion of activin A was evident in human mast cell-1 line cells 3 h after stimulation and progressively increased over time. Activin A was present in the cytoplasm of activated but not unstimulated murine bone marrow MC as demonstrated by immunofluorescence studies, suggesting that secretion of activin A by MC was due to de novo synthesis rather than secretion of preformed protein. Activin A also colocalized with human lung MC from patients with asthma by double-immunofluorescence staining. Furthermore, secretion of activin A was significantly increased in the airway of wild-type mice after OVA sensitization followed by intranasal challenge. Secretion of activin A, however, was greatly reduced in MC-deficient WBB6F1-W/Wv mice as compared with wild-type mice, indicating that MC are an important contributor of activin A in the airways of a murine asthma model. Additionally, activin A promoted the proliferation of human airway smooth muscle cells. Taken together, these data suggest that MC-derived activin A may play an important role in the process of airway remodeling by promoting the proliferation of airway smooth muscle.

Living donor transplantation is now an acceptable option that should be considered for selected cystic fibrosis patients with end-stage lung disease. Two lungs obtained from live donors can adequately support an adult cystic fibrosis patient. The morbidity from lobectomy to the healthy donor is minimal.

Failure of a single vital organ is the usual indication for which to consider transplantation. Examples of disorders commonly leading to lung transplantation include emphysema, cystic fibrosis, pulmonary hypertension, and interstitial lung disease. Cardiomyopathy is the most frequent indication for heart transplantation. Biliary cirrhosis and fulminant hepatitis are common indications for liver transplantation. Patients with systemic disorders pose a challenge because the disease may involve vital organs other than the one being considered for transplantation. The reasons such patients are frequently not suitable for transplantation are: Other vital organs affected by the disorder may also fail, transplant recipients may not experience improved quality of life or their rehabilitation may be hindered because of disease in the other organs, other organ involvement can increase the risk of infection, or the immunosuppressive medications may precipitate or worsen dysfunction of other organs. Patients with systemic disorders such as severe diabetes, systemic vasculitides, such as lupus erythematosus, and common variable hypogammaglobulinemia therefore are typically not candidates for transplantation. Many transplant centers, however, do not categorically exclude patients with systemic or multisystem disorders, including sarcoidosis, from becoming candidates for organ transplantation and selection criteria are still in evolution. 20 The ideal time to refer a patient for transplantation remains relatively imprecise. It is recommended that referral should occur sometime before the patient's condition has deteriorated to the point at which survival would be less than the anticipated time necessary to stay on a transplant waiting list. In addition, the patient's condition should not be allowed to deteriorate to the point that his or her ability to tolerate surgery would become too risky. The timing for referral is usually based upon a constellation of factors that include organ availability, the natural history and prognosis of the disease process, the rapidity of deterioration despite maximum management, failure of therapy, the overall physical and nutritional status of the candidate, and the laboratory findings assessing the severity and functional status of the failing organ. Clearly, the potential candidate has to be able to survive the waiting period for the specific organ while under maximum medical management. The waiting period for cadaveric organ transplantation varies with the organ donor pool. The waiting period for lung transplantation is between 1 and 2 years. During the waiting period, the patient and referring physician must aggressively strive to prepare the candidate to be in the best condition possible prior to transplantation. The objective is to reduce the risk of surgery and expedite recovery and rehabilitation. That may involve maximizing therapy, improving nutritional status, attaining near-ideal body weight, or participating in an organized rehabilitation program. Patients with systemic disorders are often being treated with immunosuppressive agents prior to transplantation. The use of corticosteroids is a relative contraindication to transplantation and is not encouraged, mainly because of the risks of infection, delayed wound healing, and uncontrolled diabetes. Doses less than or equal to 10 mg per day or 20 mg every other day is a goal suggested for patients who are dependent upon corticosteroids.

Background Bronchial thermoplasty (BT) has previously been shown to improve asthma control out to 2 years in patients with severe persistent asthma. Objective We sought to assess the effectiveness and safety of BT in asthmatic patients 5 years after therapy. Methods BT-treated subjects from the Asthma Intervention Research 2 trial (ClinicalTrials.gov NCT01350414) were evaluated annually for 5 years to assess the long-term safety of BT and the durability of its treatment effect. Outcomes assessed after BT included severe exacerbations, adverse events, health care use, spirometric data, and high-resolution computed tomographic scans. Results One hundred sixty-two (85.3%) of 190 BT-treated subjects from the Asthma Intervention Research 2 trial completed 5 years of follow-up. The proportion of subjects experiencing severe exacerbations and emergency department (ED) visits and the rates of events in each of years 1 to 5 remained low and were less than those observed in the 12 months before BT treatment (average 5-year reduction in proportions: 44% for exacerbations and 78% for ED visits). Respiratory adverse events and respiratory-related hospitalizations remained unchanged in years 2 through 5 compared with the first year after BT. Prebronchodilator FEV1 values remained stable between years 1 and 5 after BT, despite a 18% reduction in average daily inhaled corticosteroid dose. High-resolution computed tomographic scans from baseline to 5 years after BT showed no structural abnormalities that could be attributed to BT. Conclusions These data demonstrate the 5-year durability of the benefits of BT with regard to both asthma control (based on maintained reduction in severe exacerbations and ED visits for respiratory symptoms) and safety. BT has become an important addition to our treatment armamentarium and should be considered for patients with severe persistent asthma who remain symptomatic despite taking inhaled corticosteroids and long-acting β2-agonists. © 2013 American Academy of Allergy, Asthma and Immunology.

Background. Inflammation and remodeling are integral parts of asthma pathophysiology. We sought to describe the clinical and pathologic features of near fatal asthma exacerbation (NFE). Methods. Bronchial biopsies were collected prospectively from NFE I subjects. Another NFE II group and a moderate severity exacerbation control group (ME II) were retrospectively identified—no biopsies obtained. Results. All NFE II ( 𝑛 = 9 ) subjects exhibited remodeling and significant inflammation (eosinophilic, neutrophilic). NFE II group ( 𝑛 = 3 7 ) had a significant history of prior intubation and inhaled corticosteroids usage compared to ME II group ( 𝑛 = 4 1 ). They also exhibited leukocytosis, eosinophilia, and longer hospitalization days. Conclusions. Remodeling, eosinophilic, and neutrophilic inflammation were observed in NFE. NFE is associated with prior intubation and inhaled corticosteroids usage.

Pericardial constriction is extremely rare after lung transplantation. We present a case and review the potential contributing factors for pericardial constriction after lung transplantation. Treatment for this condition, irrespective of the cause, remains pericardiectomy.

RATIONALE: Bronchial thermoplasty (BT) is a bronchoscopic procedure in which controlled thermal energy is applied to the airway wall to decrease smooth muscle. OBJECTIVES: To evaluate the effectiveness and safety of BT versus a sham procedure in subjects with severe asthma who remain symptomatic despite treatment with high-dose inhaled corticosteroids and long-acting beta(2)-agonists. METHODS: A total of 288 adult subjects (Intent-to-Treat [ITT]) randomized to BT or sham control underwent three bronchoscopy procedures. Primary outcome was the difference in Asthma Quality of Life Questionnaire (AQLQ) scores from baseline to average of 6, 9, and 12 months (integrated AQLQ). Adverse events and health care use were collected to assess safety. Statistical design and analysis of the primary endpoint was Bayesian. Target posterior probability of superiority (PPS) of BT over sham was 95%, except for the primary endpoint (96.4%). MEASUREMENTS AND MAIN RESULTS: The improvement from baseline in the integrated AQLQ score was superior in the BT group compared with sham (BT, 1.35 +/- 1.10; sham, 1.16 +/- 1.23 [PPS, 96.0% ITT and 97.9% per protocol]). Seventy-nine percent of BT and 64% of sham subjects achieved changes in AQLQ of 0.5 or greater (PPS, 99.6%). Six percent more BT subjects were hospitalized in the treatment period (up to 6 wk after BT). In the posttreatment period (6-52 wk after BT), the BT group experienced fewer severe exacerbations, emergency department (ED) visits, and days missed from work/school compared with the sham group (PPS, 95.5, 99.9, and 99.3%, respectively). CONCLUSIONS: BT in subjects with severe asthma improves asthma-specific quality of life with a reduction in severe exacerbations and healthcare use in the posttreatment period. Clinical trial registered with www.clinialtrials.gov (NCT00231114).

We tested the hypothesis that enhanced cell division accounted for the augmented numbers of monocytic phagocytes with characteristics attributed to alveolar macrophages (AM) found in the lungs of habitual tobacco (T) and marijuana (M) smokers. The monocytic phagocytes, that is, alveolar macrophages, were obtained by bronchoalveolar lavage (BAL) from 12 nonsmoking subjects; 10 subjects who smoked T only (TS); 13 subjects who smoked M only (MS); and 6 smokers of both T and M (MTS). The replication of these cells was determined by measuring the incorporation of [3H]thymidine into the DNA of dividing cells and visually counting 2,000 cells on autoradiographically prepared cytocentrifuge cell preparations. This study demonstrated that the number of [3H]thymidine-labeled monocytic phagocytes with characteristics of alveolar macrophages from either TS or MS have a higher proliferative index compared to cells (macrophages) from nonsmokers, p less than 0.05 by one-way ANOVA. The total number of BAL macrophages that are in mitosis in TS (17.90 +/- 4.50 labeled AM x 10(3)/ml) or MTS (10.50 +/- 4.20 labeled AM x 10(3)/ml) are 18- and 10-fold greater, respectively, than the number obtained from nonsmokers (1.01 +/- 0.18 labeled AM x 10(3)/ml). Interestingly, the number of [3H]thymidine-labeled macrophages from MS (2.90 +/- 0.66 labeled AM x 10(3)/ml) are also greater than the number obtained from nonsmokers, although this is not statistically significant. The stimulus augmenting alveolar macrophage replication is as yet unknown but may likely be found in the T or M smoke.(ABSTRACT TRUNCATED AT 250 WORDS)

Living lobar lung transplantation places two donors at risk for each recipient. We examined the perioperative outcomes associated with the 253 donor lobectomies performed at our institution during our first decade of living lobar lung transplantation. There have been no perioperative or long-term deaths. 80.2% of donors (n = 203) had no perioperative complications, while fifty (19.8%) had one or more complication. The incidence of intraoperative complications was 3.6%. Complications requiring reoperation occurred in 3.2% of donors. 15.0% of donors had other perioperative complications; the most serious were two donors who developed pulmonary artery thrombosis, while the most common was the need for an additional thoracostomy tube or a thoracostomy tube for >/=14 d for persistent air leaks and/or drainage. Right-sided donors were more likely to have a perioperative complication than left-sided donors (odd ratio 2.02, p = 0.04), probably secondary to right lower and middle lobe anatomy. This experience has shown donor lobectomy to be associated with a relatively low morbidity and no mortality, and is important if this procedure is to be considered an option at more pulmonary transplant centers, given continued organ shortages and differences in philosophical and ethical acceptance of live

Living-donor lobar lung transplantation was developed as an alternative to cadaveric transplantation. However, whether two pulmonary lobes provide comparable intermediate and long-term pulmonary function to full-sized bilateral cadaveric grafts in adults is unknown.An analysis of the pulmonary functions of 59 bilateral lobar and 43 bilateral cadaveric adult lung transplant recipients who survived more than 3 months after transplantation was performed.Mean follow-up was 3.8 +/- 2.8 years. In lobar recipients, mean percent predicted forced vital capacity and forced expiratory volume in 1 second improved between 1 and 6 months after transplantation (42.5% +/- 13.4% and 46.9% +/- 14.0% at 1 month versus 63.6% +/- 14.1% and 64.5% +/- 13.7% at 6 months; p0.001 and0.001, respectively). In cadaveric recipients, mean percent predicted forced vital capacity improved after transplantation (54.3% +/- 14.5% at 1 month versus 74.2% +/- 21.3% at 12 months; p0.01). As compared with the cadaveric group, mean percent predicted forced vital capacity and forced expiratory volume in 1 second were lower 1 and 3 months after transplantation in the lobar recipients (p = 0.001 at both times); however, by 6 months after transplantation, these values were comparable and remained so throughout the follow-up period. In a subset of lobar and cadaveric recipients, maximal exercise, heart rate, peak oxygen consumption, anaerobic oxygen consumption threshold, and ability to maintain oxygen saturation were also comparable.In those adult recipients surviving more than 3 months after transplantation, lobar lung transplantation provides comparable intermediate and long-term pulmonary function and exercise capacity to bilateral cadaveric lung transplantation.

In this article, the authors provide an update to Maurer and Chaparro's 1995 review in this journal of lung transplantation for cystic fibrosis. Bilateral (sequential) cadaver donor transplantation is the usual procedure of choice. The four-year survival rate for adult, all-disease, double-bilateral lung transplantation has improved to 53%. Because of lower [corrected] survival rate among adults, living-donor lobar transplantation should be performed only when cadaver lungs are unlikely to become available. The International Society for Heart and Lung Transplantation and the Cystic Fibrosis Foundation have promulgated uniform guidelines for transplantation candidate selection. Issues of diabetes mellitus, mechanical ventilation, osteoporosis, malnutrition, fungi and drug-resistant bacteria, pleural fibrosis, and sinusitis in relation to transplantation candidacy are discussed. Some practical points regarding transplantation center referral are presented, and a list of cystic fibrosis transplantation centers in the United States is supplied.

The major clinical problem for patients with cystic fibrosis (CF) is progressive loss of pulmonary function, usually due to chronic bacterial infections. A patient with CF and a lung transplant was severely infected with a previously unidentified gram-negative bacterium. We isolated this organism (strain DS15158) from the patient and characterized it by phylogenetic analysis of the small-subunit rRNA and biochemically by the BIOLOG GN MicroPlate assay, fatty acid analysis, and various standard laboratory tests. No close match to any other organism could be found. Isolate DS15158 represents a new genus-level divergence within the bacterial subdivision α- Proteobacteria on the basis of the 16S rRNA gene analysis.

As the recipient list for patients requiring lung transplantation continues to increase, cadaveric donor lung availability has remained static. Our experience with utilizing lobes from living related donors for bilateral pulmonary transplantation in 20 patients has yielded a 75% survival at 1 year follow-up. Morbidity and mortality have been predominately due to infection. Rejection episodes have been mild and unilateral and have responded to augmented corticosteroids. Pulmonary function tests in the recipients tend to improve steadily during the first year postoperatively, and the patients have excellent functional capacity. There have been no significant complications in the donors. On the basis of our clinical experience, we have found that bilateral lobar transplantation utilizing living related donors has resulted in organ availability that can be lifesaving in critically ill patients and can provide a good alternative in certain noncritical, deteriorating patients.

The incidence and severity of asthma continue to increase despite advances in therapy. Two types of severe asthma exacerbations have been described: "sudden onset" and "slow onset." Beta-adrenergic agonists and corticosteroids are still the mainstay of therapy in the intensive care unit. Hypercapnic hypoventilation is advocated as a mode of mechanical ventilation to maintain oxygenation while minimizing barotrauma. Sedating and paralytic agents must be used with caution to prevent complications such as myopathy, which may occur with prolonged use of these agents. Future avenues of study could include the use of leukotriene and platelet-activating factor inhibitors. Asthma management guidelines should be practiced to prevent worsening of bronchospasm to the point of severe exacerbation.

Rejection of the lung allograft remains a significant problem and the primary cause of morbidity and mortality for the transplant recipient. Various strategies have been developed to prevent and minimize episodes of rejection. These methods involve either specific inhibitors or using a combination of barriers at precise sites in the immune response to induce graft tolerance. Another technique would be to create a tranquil environment between opposing populations of immunocompetent cells from both the donor and recipient by enhancing chimerism. Finding potent immunosuppressive agents is not the only impediment to prolonged graft survival. The challenge is also to develop techniques and agents that do not have global immunosuppressive properties that would cause the host to become more susceptible to infectious agents, as well as to prevent toxicity to other vital organs. A review of available new pharmaceutical therapies and an overview of potential future methods are presented here.

The effect of heavy, habitual marijuana use compared with tobacco smoking on the composition of bronchoalveolar and peripheral blood lymphocytic phenotypes was examined. Bronchoalveolar lavage (BAL) and peripheral blood (PB) samples were taken from 14 nonsmokers (NS), 14 tobacco smokers (TS), 19 heavy, habitual marijuana smokers (MS), and 9 marijuana and tobacco smokers (MTS). In BAL fluid, marijuana use was associated with significantly higher alveolar macrophage concentrations, whereas tobacco smoking was associated with significantly higher alveolar macrophage, as well as higher bronchoalveolar lymphocyte and neutrophil concentrations. The bronchoalveolar T-lymphocytic phenotypic profiles of marijuana users differed from those of tobacco smokers. Tobacco, not marijuana, was found to have a significant effect toward lower percentages of bronchoalveolar CD4 cells, toward higher concentrations of bronchoalveolar CD8 cells, and toward lower bronchoalveolar CD4:CD8 ratios. Marijuana use had a significant effect toward lower percentages of bronchoalveolar CD8 cells. In peripheral blood, marijuana, but not tobacco, use was associated with significantly higher percentages of CD4 cells, lower percentages of CD8 cells, and higher CD4:CD8 ratios. These findings suggest that tobacco and marijuana have effects on bronchoalveolar and peripheral blood immunoregulatory T-lymphocytic subpopulations that differ in type or magnitude.

significant univariately were entered into a multiple logistic regression model and retained if significant at the 10% level. Model calibration and discrimination were assessed using the Hosmer-Lemeshow test and receiver operating characteristic (ROC) curve respectively. Results: 757 transplants were studied, 99 of whom died within 30 days. Four risk factors were retained: diagnosis -suppurative (baseline), pulmonary hypertension (Odds Ratio 2.5 (95% CI 1.2 to 5.5)), fibrosis (1.1 (0.4 to 2.8)), COPD (1.5 (0.5 to 2.3)), other (2.5 (1 to 6.2)); ventilation prior to transplantation (3.2 (0.9 to 11.5)); creatinine clearance 80 mls/min (1.7 (1.0 to 2.9)); recipient diabetes (2.0 (0.9 to 4.4)), and ischaemia time (1.5 (1.1 to 2.2)) per increase in time category from 3 hours to 3-4 hours to 4 hours. Calibration using the Hosmer-Lemeshow 2 1.39 (p 0.5) and the area under the ROC curve was 0.71. Conclusion: The risk model developed is well calibrated and produces accurate risk estimates. At present the model only has a moderate ability to discriminate between patients who die from those who survive. This model will continue to be refined as more data are accrued.

Asthma morbidity and mortality continue to increase. The clinical characteristics of the high risk asthmatic patient continue to be elucidated. These include historical features, current disease characteristics and psychosocial factors. Beta-Adrenergic agonists continue to be the mainstay of acute therapy. The following review details these topics.

In the September 11, 1995, issue of theARCHIVES, Kramer and Sprung 1 described a 28-year-old man with bronchiolitis obliterans and pneumonia who was considered for a bilateral whole-lung transplantation from living related donors. It was thought that whole lungs were necessary to support an adult recipient's ventilation. Kramer and Sprung indicated that, to their knowledge, living donor whole-lung transplantation from one adult to another has never been performed. Therefore, because of lack of experience, the transplantation was not performed, and the patient ultimately died. Kramer and Sprung knew of Starnes and colleagues' 2 experience in transplanting lobes from living donors but assumed that this procedure was only applicable to children or small adults. To date, Starnes et al have transplanted bilateral lower lobes from living related donors into 24 adult patients with cystic fibrosis (mean age, 25.5 years; age range, 18 to 36 years). (An additional patient, aged 32

We studied the utility of bronchoalveolar lavage (BAL) as the primary diagnostic procedure in 46 separate episodes of suspected Pneumocystis carinii pneumonia (PCP) in 42 patients with AIDS. 35 procedures were performed at the bedside. A separate group of 40 historical controls with AIDS and suspected PCP had transbronchial biopsy (TBB) as the primary procedure. At least 100 cc of saline in 50 cc aliquots was used for BAL. Specimens were processed using rapid silver methenamine, Papanicolau, and Ziehl Neelson stains with appropriate cultures. There were 29 positives and 17 true negatives for PCP with BAL, confirmed by biopsy in 11, and using clinical criteria in 6. Accuracy, sensitivity, and predictive value of a negative result were all 100%. There was no significant difference in yield between TBB and BAL (p greater than 0.10). BAL was useful to diagnose other opportunistic organisms including CMV, atypical mycobacteria, and fungi. The frequency of isolates in the TBB group were comparable. TBB was complicated by 4 episodes of major bleeding. The data indicate that bedside BAL is effective, and safer than TBB in patients with AIDS and suspected PCP. We advocate BAL as the primary diagnostic procedure which can be performed at the bedside in patients with suspected PCP and AIDS. The high accuracy and predictive value of a negative BAL for PCP suggests confirmatory procedures may not be necessary in many cases.

Cells derived from bronchoalveolar lavage (BAL) were obtained from 19 healthy non-smokers (NS) and from 43 healthy smokers of tobacco and/or marijuana. Thirteen subjects smoked tobacco cigarettes only (TS) (mean ± SE: 17.4 ± 5.5 pack-years). Thirty subjects smoked marijuana; of these, 14 smoked marijuana only (MS) (149.1 ± 102.7 joint-years) and 16 smoked marijuana and tobacco (MTS) (43.3 ± 7.2 joint-years and 18.4 ± 3.2 pack-years). Cell counts were expressed as total number recovered and as number of cells per milliliter of BAL fluid returned. Cell differentials were performed on Giemsa-stained cytopreps. Total cell number was significantly increased in the MTS, TS, and MS compared with that in the NS (p 10 pack-years) was associated with higher total cell numbers in BAL than was light tobacco smoking (< 10 pack-years). The MTS had a higher total BAL cell yield per milliliter than did the TS or the MS (p < 0.004). Marijuana smoking had a significant effect on cell yield...

A case of clinically and radiologically typical asbestosis manifesting in a 55 year old man occurred 36 years after a brief exposure period of less than one year. A transbronchial lung biopsy was performed but the samples were considered non-diagnostic. The diagnosis was supported by the use of bronchoalveolar lavage to obtain alveolar samples and scanning electron microscopy-energy dispersive x ray analysis of fibres found in the bronchoalveolar lavage fluid which showed a predominance of amosite.

Objective Living lobar lung transplantation was developed as a procedure for patients considered too ill to await cadaveric transplantation. Methods One hundred twenty-eight living lobar lung transplantations were performed in 123 patients between 1993 and 2003. Eighty-four patients were adults (age, 27 ± 7.7 years), and 39 were pediatric patients (age, 13.9 ± 2.9 years). Results The primary indication for transplantation was cystic fibrosis (84%). At the time of transplantation, 67.5% of patients were hospitalized, and 17.9% were intubated. One-, 3-, and 5-year actuarial survival among living lobar recipients was 70%, 54%, and 45%, respectively. There was no difference in actuarial survival between adult and pediatric living lobar recipients ( P = .65). There were 63 deaths among living lobar recipients, with infection being the predominant cause (53.4%), followed by obliterative bronchiolitis (12.7%) and primary graft dysfunction (7.9%). The overall incidence of acute rejection was 0.8 episodes per patient. Seventy-eight percent of rejection episodes were unilateral. Age, sex, indication, donor relationship, preoperative hospitalization status, use of preoperative steroids, and HLA-A, HLA-B, and HLA-DR typing did not influence survival. However, patients on ventilators preoperatively had significantly worse outcomes (odds ratio, 3.06, P = .03; Kaplan-Meier P = .002), and those undergoing retransplantation had an increased risk of death (odds ratio, 2.50). Conclusion These results support the continued use of living lobar lung transplantation in patients deemed unable to await a cadaveric transplantation. We consider patients undergoing retransplantations and intubated patients to be at significantly high risk because of the poor outcomes in these populations.

We performed flexible fiberoptic bronchoscopy in 29 habitual, heavy marijuana smokers 25 to 45 yr of age, with and without concomitant tobacco smoking, to inspect and biopsy their proximal tracheobronchial tree for the evaluation of histopathologic changes. Control tobacco smokers (TS) and nonsmokers (NS) residing in the same metropolitan area were similarly studied and compared with the marijuana smokers (MS) and marijuana-tobacco smokers (MTS). Respiratory and drug histories, physical examination, and pulmonary function tests were obtained prior to bronchoscopy. The prevalence of respiratory symptoms and pulmonary function abnormalities was generally higher in the 3 smoking groups than in the NS group but was not statistically different across all groups. However, bronchoscopic inspection revealed airway hyperemia and other visible abnormalities in 32 (91%) subjects in the 3 smoking groups, unlike the unremarkable findings in the NS group. Light microscopy showed 2 or more histopathologic changes in the bronchial epithelium of all MS, MTS, and TS. Squamous metaplasia was observed in all MTS, a prevalence that was significantly different from that in MS, TS, and NS. Hyperplasia of basal and goblet cells was more prevalent in the MS than in the NS, whereas cellular disorganization was more prevalent in the MS than in the TS. A direct relationship between cumulative marijuana use (joint-years) and bronchoscopic and histopathologic changes was not apparent in this study sample. These results indicate that relatively young, habitual, heavy marijuana smokers have a high prevalence of abnormal airway appearance and histologic findings, irrespective of concomitant tobacco smoking.(ABSTRACT TRUNCATED AT 250 WORDS)

†Supported by U.S. Public Health Service CRC Grant RR-00865 and National Institutes of Health Grant 2R01-DA-03018.

Regulation of the production of the biologically active vitamin D3 sterol 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] by cultured pulmonary alveolar macrophages (PAM) obtained from 6 patients with pulmonary sarcoidosis and from 9 normal subjects was studied. The sarcoid cells, all collected from patients with normal calcium metabolism, synthesized 1,25-(OH)2-[3H]D3 from the substrate 25-hydroxyvitamin [3H]D3 (25OH-[3H]D3), whereas in vitro incubation with recombinant human interferon-gamma (IFN gamma) or lipopolysaccharide (LPS) was required for induction of synthesis of the hormone by normal PAM. Exogenous 1,25-(OH)2D3 (10-100 nmol/L) decreased endogenous hormone production by normal PAM by approximately 45%. The relative inhibitory effect of 1,25-(OH)2D3 was less pronounced in sarcoid PAM, in which 10-100 nmol/L 1,25-(OH)2D3 inhibited 250HD3-1-hydroxylase by approximately 25%. An accompanying induction of the 250HD3-24-hydroxylase, which is typical for renal cells, was found at low levels in only 3 of 10 experiments; in this regard, no differences between sarcoid and normal PAM were apparent. PTH or forskolin did not influence 250HD3 metabolism by PAM. 1,25-(OH)2D3 production by sarcoid PAM was enhanced by lipopolysaccharide and IFN gamma. Likewise, recombinant human interleukin-2 stimulated 1,25-(OH)2D3 production by sarcoid PAM, suggesting a possible role for both IFN gamma and interleukin-2 in the induction of 1,25-(OH)2D3 synthesis by sarcoid PAM in vivo. Recombinant human IFN alpha, IFN beta, and granulocyte-macrophage colony-stimulating factor had little effect. Dexamethasone and chloroquine, which have in vivo antihypercalcemic activity in sarcoidosis, both inhibited 1,25-(OH)2D3 synthesis by sarcoid PAM; chloroquine simultaneously stimulated the 24-hydroxylase. Our studies suggest that the 250HD3-metabolizing system in PAM is in some respects different from renal metabolism of 250HD3.

The cellular and lymphocyte phenotypic composition of bronchoalveolar lavage (BAL) fluid and peripheral blood (PB) from 15 healthy, nonsmoking, asbestos-exposed shipyard workers (AEW) and 10 nonsmoking, age-matched unexposed workers (UEW) were compared. None of the AEW had clinical, radiographic, or physiologic evidence of asbestosis, but six had radiographic evidence of pleural plaques and/or thickening. The mean duration of asbestos exposure was 16.3 +/- 2.3 yr, and the mean period since exposure was 10.8 +/- 0.5 yr. All but three of the AEW and none of the UEW had asbestos bodies detected in the first 20 ml of BAL fluid recovered (0.1 to 35 asbestos bodies/ml). The AEW had a significantly higher mean percentage (19.1 +/- 2.8% versus 9.7 +/- 1.6%) and concentration (31.6 +/- 5.2 x 10(3) cells/ml versus 14.7 +/- 2.5 x 10(3) cells/ml) of BAL lymphocytes compared with that in the UEW, with an increased mean concentration of each phenotype measured. In PB, the mean lymphocyte concentration was also higher in the AEW than in the UEW (2.0 +/- 0.3 x 10(3) cells/ml versus 1.5 +/- 0.3 x 10(3) cells/ml), but the difference was not statistically significant, and there was no increase of any phenotype measured. BAL lymphocytosis did not correlate with exposure history or BAL asbestos body count, but was greater in AEW with pleural abnormality (30.1 +/- 2.9% versus 11.8 +/- 1.6%). BAL concentrations of CD-20, CD-3, and CD-4, but not of CD-8 cells were significantly increased compared with those in the AEW without pleural abnormality. Further longitudinal studies are needed to determine the prognostic significance of these findings.