Clinical outcomes and predictive value of programmed cell death-ligand 1 expression in response to anti-programmed cell death 1/ligand 1 antibodies in non-small cell lung cancer patients with performance status 2 or greater.

BACKGROUND: Anti-programmed cell death protein-1/ligand-1 (anti-PD-1/PD-L1) therapy is promising for patients with non-small-cell lung cancer (NSCLC); however, clinical trials have focused on patients with a performance status (PS) 0 or 1. This study aimed to evaluate the clinical outcomes and correlation between PD-L1 expression status and tumor response to anti-PD-1/PD-L1 therapy among NSCLC patients with poor PS (i.e., PS ≥ 2). METHODS: In total, 130 patients with NSCLC and PS ≥ 2 treated with anti-PD-1/PD-L1 monotherapy at 12 institutions between January 2016 and August 2019 were retrospectively reviewed. PD-L1 expression status was divided into four groups: < 1%, 1-49%, ≥ 50%, and unknown. RESULTS: The objective response rate and PS improvement rate were 23 and 21% and were higher in the PD-L1 ≥ 50% group than in other groups (P < 0.01). Median progression-free survival (PFS) was 62 days and was longer in the PD-L1 ≥ 50% group than in other groups (P = 0.03). Multivariate analyses revealed that PD-L1 expression is significantly associated with prolonged PFS (PD-L1 < 1%; reference; 1-49%, hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.04-0.99, P = 0.05; ≥ 50%, HR 0.12, 95% CI 0.02-0.71, P = 0.02; unknown, HR 0.30, 95% CI 0.08-1.22, P = 0.09). CONCLUSIONS: NSCLC patients with poor PS and PD-L1 ≥ 50% are expected to benefit from anti-PD-1/PD-L1 therapy, despite a modest overall response among NSCLC patients with poor PS. Accordingly, PD-L1 expression provides useful information regarding decision-making for anti-PD-1/PD-L1 therapy even in these populations.

Validation of a breath-holding test as a screening test for exercise-induced hypoxemia in chronic respiratory diseases.

The detection of exercise-induced hypoxemia is important for evaluating disease status in patients with chronic respiratory diseases. The 6-min walk test (6MWT) is useful for detecting exercise-induced hypoxemia. This pilot study aimed to validate the breath-holding test (BHT) as a screening for exercise-induced hypoxemia and compare its utility with that of the 6MWT in patients with chronic respiratory diseases. Fifty-nine patients with chronic respiratory diseases underwent BHTs lasting 10, 15, and 20 s. Percutaneous oxygen saturation (SpO2), pulse rate, and severity of dyspnoea were measured. The participants also underwent a 6MWT, a pulmonary function test, and analysis of arterial blood gas at rest. Multivariate linear regression analysis was performed to identify significant predictors of desaturation in the 6MWT. The minimum SpO2 during the BHT (all durations) and 6MWT were significantly correlated. Receiver operating characteristic analysis revealed the optimal cut-off for predicting SpO2 < 90% during the 6MWT as a minimum SpO2 ≤ 94% during the 15-s BHT. Perceived dyspnoea and maximum pulse rate were significantly lower during the 15-s BHT than during the 6MWT. In the multivariate linear regression analysis, the minimum SpO2 during the 15-s BHT (ß, 0.565, p < 0.001) and %DLco (ß, 0.255, p < 0.028) were independent predictors of desaturation in the 6MWT. The minimum SpO2 during the 15-s BHT may be a useful measure for screening for exercise-induced hypoxemia in patients with chronic respiratory diseases. The BHT is easier to perform, more readily available, and better tolerated than the 6MWT.

Aerosolized tobramycin for Pseudomonas aeruginosa ventilator-associated pneumonia in patients with acute respiratory distress syndrome.

BACKGROUND: Ventilator-associated pneumonia (VAP) due to Pseudomonas aeruginosa has a high mortality and recurrence rate, especially in patients with acute respiratory distress syndrome (ARDS). Therefore, new therapeutic strategies against severe pneumonia are needed. This study evaluated the efficacy of aerosolized tobramycin for P. aeruginosa VAP in ARDS patients. METHODS: A retrospective analysis was performed on patients who developed VAP caused by P. aeruginosa during the course of ARDS at the intensive care unit (ICU) of Kumamoto University Hospital. Aerosolized tobramycin inhalation solution (TIS) 240 mg was administered daily for 14 days in addition to systemic antibiotics. RESULTS: A total of 44 patients (TIS group, n = 22; control group, n = 22) were included in the analysis. No significant differences were found between the two groups in terms of clinical characteristics, including acute physiology and chronic health evaluation II score upon ICU admission. The TIS group had significantly lower recurrence of P. aeruginosa VAP (22.7% vs. 52.4%, P = 0.04) and ICU mortality (22.7% vs. 63.6%, P < 0.01) than the control group. Bacterial concentration in tracheal aspirate (mean log 10 cfu/mL ± SD on days 2-5: 1.2 ± 1.3 vs. 5.0 ± 2.3, P < 0.01) decreased more rapidly and markedly in the TIS group compared with the control group. CONCLUSION: Aerosolized tobramycin was an effective therapeutic strategy for P. aeruginosa VAP patients with ARDS.

Clinical effects of direct hemoperfusion using a polymyxin B-immobilized fiber column in clinically amyopathic dermatomyositis-associated rapidly progressive interstitial pneumonias.

BACKGROUND: Rapidly progressive interstitial pneumonias (RPIPs) associated with clinically amyopathic dermatomyositis (CADM) are highly resistant to therapy and have a poor prognosis. Multimodal therapies, including direct hemoperfusion using a polymyxin B-immobilized fiber column (PMX-DHP), have a protective effect on RPIPs. We evaluated the effects of PMX-DHP on CADM-associated RPIPs. METHODS: We retrospectively enrolled 14 patients with CADM-associated RPIPs and acute respiratory failure treated with PMX-DHP, corticosteroids, and immunosuppressive agents. Clinical manifestations were compared between survivors and non-survivors at 90 days after PMX-DHP. RESULTS: The survival rate at 90 days after PMX-DHP was 35.7% (5/14). Before PMX-DHP, the survivor group exhibited a significantly higher PaO2/FiO2 (P/F) ratio and serum surfactant protein-D (SP-D) levels and significantly lower lactate dehydrogenase (LDH) and ferritin levels than the non-survivor group. Platelet counts were significantly decreased after PMX-DHP therapy in both groups, but remained higher in the survivor group than the non-survivor group over the course of treatment. Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody positive patients demonstrated a poor 90-day survival rate, lower platelet counts and P/F ratio, and higher LDH levels than anti-MDA-5 antibody negative patients. CONCLUSIONS: CADM-associated RPIPs with anti-MDA-5 antibody is associated with a very poor prognosis. A higher P/F ratio and SP-D level, lower LDH and ferritin levels, higher platelet counts, and anti-MDA-5 antibody negativity are important prognostic markers in patients with CADM-associated RPIPs treated with PMX-DHP.

Dose escalation and pharmacokinetic study of carboplatin plus pemetrexed for elderly patients with advanced nonsquamous non-small-cell lung cancer: Kumamoto thoracic oncology study group trial 1002.

OBJECTIVES: This study was designed to determine the recommended dose of carboplatin and pemetrexed for elderly (≥70-year-old) chemotherapy-naïve patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) and to investigate the pharmacokinetics of pemetrexed. METHODS: The patients were treated with 4-6 cycles of carboplatin plus a fixed dose of pemetrexed (500 mg/m(2)) every 3 weeks; the dose of carboplatin was escalated [from area under the curve (AUC) 4 to AUC 6]. To examine the pharmacokinetics of pemetrexed, blood samples were collected before and after pemetrexed infusion, and the blood levels of pemetrexed were measured by liquid chromatography-mass spectrometry. RESULTS: Grade 3 infection as a dose-limiting toxicity was observed at a carboplatin dose of AUC 6. We therefore determined a carboplatin dose of AUC 5 and a pemetrexed dose of 500 mg/m(2) as the recommended doses from this study. The pharmacokinetic study showed a significant inverse correlation between the AUC of pemetrexed and the creatinine clearance. CONCLUSIONS: For elderly chemotherapy-naïve patients with advanced nonsquamous NSCLC, the combination of carboplatin AUC 5 plus pemetrexed 500 mg/m(2) is recommended as a promising regimen; however, a reduction of the pemetrexed dose may be required for patients with renal dysfunction because of the high risk of hematotoxicities.

Favorable outcome with hemoperfusion of polymyxin B-immobilized fiber column for rapidly progressive interstitial pneumonia associated with clinically amyopathic dermatomyositis: report of three cases.

We present 3 cases of rapidly progressive interstitial pneumonia (RPIP) associated with clinically amyopathic dermatomyositis (C-ADM) that were treated with two courses of direct hemoperfusion with polymyxin B-immobilized fiber column (PMX-DHP). Despite initial treatment with high-dose corticosteroids, pulsed cyclophosphamide, and cyclosporine, the lung disease and hypoxemia deteriorated in all the patients. After PMX-DHP treatment, the PaO2/FiO2 ratio and serum LDH and KL-6 were improved, the abnormal shadows in chest high-resolution computed tomography (HRCT) scans gradually decreased, and, finally, all patients survived. These findings indicate that PMX-DHP treatment could be effective in the management of RPIP in patients with C-ADM in combination with conventional therapy.

Pathological and clinical relevance of selective recruitment of Langerhans cells in the respiratory bronchioles of smokers.

BACKGROUND: Smoking causes an influx of inflammatory cells including Langerhans cells (LCs) into the airways and lung parenchyma, thus inducing histological changes, such as emphysema and fibrosis. We examined the distribution and quantity of Langerhans cells in relation to clinical and pathological findings and explored the association between smoking and accumulation of Langerhans cells in the respiratory bronchioles. METHODS: Fifty-three patients who underwent lung resection for primary diseases, including lung cancer, were recruited. Histological and immunohistochemistry analyses were utilized to identify CD1a-positive Langerhans cells in peripheral lung specimens separated from primary lesions. Clinical characteristics, pathological changes, and distribution of CD1a-positive Langerhans cells distribution were assessed. RESULTS: Of the 53 patients, 35 were smokers and 18 were non-smokers. The number of Langerhans cells in the respiratory bronchioles was significantly increased in smokers as compared to that in non-smokers (p < 0.001). The number of Langerhans cells in smokers was significantly higher in patients with mild emphysema than in those without emphysema (p < 0.01). The high-LC group showed more frequent smoking-related histological changes, such as respiratory bronchiolitis, parenchymal fibrosis, accumulation of macrophages, and smoking-related interstitial fibrosis, than the low-LC group. However, there were no differences in the smoking indices and pulmonary functions of the groups. CONCLUSIONS: Selective accumulation of Langerhans cells in the respiratory bronchioles of smokers may lead to the development of smoking-related pathological changes.

CD8 and CD103 are highly expressed in asthmatic bronchial intraepithelial lymphocytes.

BACKGROUND: Although characteristics of intraepithelial lymphocytes (IELs) in mucosal immunity have been well defined in the intestine, bronchial IELs have been little investigated. Recently, we showed that bronchial IELs have a distinct function that partly resembles that of intestinal IELs; however, surface antigen expression of bronchial IELs and the relationship of that expression to airway disease have not been studied. METHODS: We analyzed phenotypic profiles of human bronchial IELs and lamina propria lymphocytes (LPLs) by double-staining immunohistochemistry using full-thickness bronchial specimens (10 nonasthmatic controls and 7 asthmatics) from lung resections. RESULTS: In controls, the percentage of CD4+ cells was lower, and the percentage of CD8+ cells was higher in IELs compared to LPLs (CD4: median 50.0% in IELs vs. 65.9% in LPLs, p = 0.01; CD8: 50.9% in IELs vs. 34.4% in LPLs, p = 0.007). The percentage of cells positive for CD103 (αE-integrin) was higher in IELs than that in LPLs (median 60.1% in IELs vs. 16.9% in LPLs; p < 0.001). In IELs from asthmatics, these characteristics were particularly significant (CD4: median 26.2%, p = 0.008; CD8: 79.8%, p = 0.007; CD103: 76.2%, p = 0.019; all compared with IELs from nonasthmatics). CONCLUSIONS: These results suggest that human bronchial IELs have roles distinct from subsets of other lymphocytes, and that CD8+ cells and CD103+ cells have potentially important functions in the bronchial epithelium.

[A case of hepatopulmonary syndrome with elevated exhaled nitric oxide].

A 76-year-old man was admitted to our hospital because of dyspnea. Three years before admission, dyspnea was recognized and had been given a diagnosis of interstitial pneumonia by a general physician. A year later, he received home oxygen therapy. After admission, we found that he had alcoholic liver cirrhosis and an increased alveolar-arterial oxygen level in his arterial blood gas. Moreover, he had an intrapulmonary vascular shunt, detected by contrast-enhanced echocardiography and perfusion scan with 99mTc-macroaggregated albumin. These results confirmed hepatopulmonary syndrome. Furthermore, exhaled nitric oxide (NO) was elevated in the patient although he had never had bronchial asthma or any other allergic diseases. Animal models of hepatopulmonary syndrome have shown that exhaled NO is associated with dilated vessels. To the best of our knowledge, this paper describes the first case of hepatopulmonary syndrome with elevated exhaled NO in Japan.

Four-meter gait speed predicts daily physical activity in patients with chronic respiratory diseases.

BACKGROUND: Physical activity measures are valuable for assessing the progression of chronic respiratory diseases. The 4-m gait speed (4MGS) test is an established functional assessment in the elderly. However, the relationship between the 4MGS and daily activity in patients with chronic respiratory diseases has not been fully understood. The present study aimed to investigate whether the 4MGS predicted daily activity, including physical activity level (PAL), in patients with chronic respiratory diseases. METHODS: We enrolled 57 patients with chronic respiratory diseases, including interstitial lung disease and chronic obstructive pulmonary disease, and evaluated the correlations between the 4MGS and various clinical parameters, including respiratory function, the 6-min walk test (6MWT), and daily activities, by using an accelerometer. Linear regression analysis was performed to identify significant predictors of daily activity. RESULTS: The 4MGS was significantly correlated with daily step counts and PAL, as well as the 6 min walk distance (r = 0.477, p < 0.001; r = 0.433, p = 0.001; and r = 0.593, p < 0.001, respectively). In the multivariate linear regression analysis, the 4MGS, % predicted forced expiratory volume in 1 s, and body mass index were independent predictors of PAL. Receiver operating characteristic analysis revealed that a 4MGS <1.07 m/s was the optimal cutoff for predicting an inactive PAL (area under the curve, 0.728; 95% confidence interval, 0.589-0.866). Patients with a slower 4MGS had significantly reduced daily activity than did those with a preserved 4MGS, despite similar modified Medical Research Council dyspnea scale measures and respiratory parameters, such as oxygenation profiles. CONCLUSIONS: The 4MGS test is a simple screening test and a useful predictor of worsening daily activity in patients with chronic respiratory diseases.

Respiratory evaluation of the risk for postoperative pulmonary complications in patients who preoperatively consulted pulmonologists: Studying both patients who underwent and who precluded planned surgery.

BACKGROUND: Due to advances in medicine, patients with pulmonary diseases have become candidates for surgery under general anesthesia. They often consult pulmonologists to assess their tolerability for surgery. The purpose of this study was to evaluate the significant characteristics responsible for postoperative pulmonary complications (PPCs) and the preclusion of the planned surgery. METHODS: The clinical data of 462 consecutive patients who consulted at the Department of Respiratory Medicine before surgery under general anesthesia were used in this study. The relationship between the patient׳s characteristics and their outcomes were analyzed. The patients who were scheduled for lung resection were excluded. RESULTS: Of the 386 patients who underwent planned surgery, 353 had no PPCs (Group A) and 33 developed PPCs (Group B). Planned surgery under general anesthesia was precluded in 31 patients due to respiratory problems (Group C). The significant predictors for PPCs consisted of a higher age, male gender, asthma, gastrointestinal surgery, cardiovascular surgery and a lower percentage of the predicted forced expiratory volume in 1 second (% predicted FEV1). The significant factors associated with the preclusion of planned surgery included interstitial pneumonia (IP), dermatologic surgery and a lower % predicted FEV1. The predicted probability of PPCs in Group C was significantly higher than that in Group A and lower than that in Group B (all p-values < 0.05). CONCLUSION: The common clinical finding for predicting PPCs and encouraging the preclusion of the planned surgery under general anesthesia was a lower % predicted FEV1.

Efficacy of direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-DHP) in rapidly progressive interstitial pneumonias: results of a historical control study and a review of previous studies.

BACKGROUND: Direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-DHP) therapy has been approved for sepsis-associated acute respiratory distress syndrome, but its efficacy for other rapidly progressive interstitial pneumonias (RPIPs) is unclear. The purpose of this study was to examine the efficacy of PMX-DHP therapy for acute respiratory failure in patients with RPIPs, when compared with a historical control receiving conventional treatment without PMX-DHP. METHODS: This study comprised 77 patients with RPIPs in our institute between January 2002 and December 2015. The initial 36 patients between January 2002 and March 2007 were treated without PMX-DHP (historical control group), and the following 41 patients between April 2007 and December 2015 were treated with PMX-DHP (PMX-DHP group) once daily for two successive days concurrently with corticosteroids and/or immunosuppressive agents. The 90-day mortality and clinical factors were compared between the groups. Cox proportional hazards models were constructed to analyze 90-day mortality and identify predictors. RESULTS: The 90-day mortality rate was significantly lower in the PMX-DHP group than in the controls (41.5% versus 66.7%, p = 0.019). PMX-DHP therapy was significantly associated with mortality (hazard ratio 0.505; 95% confidence interval, 0.270-0.904; p = 0.032). There were significant differences in the serial changes in the PaO2/FiO2 ratio, SOFA score, and blood neutrophil counts from days 0-5 after PMX-DHP between the survivor and non-survivor groups ( p = 0.015, p < 0.001, p = 0.035, respectively). The improved PaO2/FiO2 ratio on day 3 significantly correlated with the change in blood neutrophil counts (rs = -0.431, p = 0.006). CONCLUSIONS: PMX-DHP therapy may be effective in RPIPs patients accompanied by acute respiratory failure and is expected to reduce mortality rates.

Primary Diaphragmatic Dedifferentiated Liposarcoma in a Young Female Patient after Delivery.

A 26-year-old woman was admitted with the chief complaint of chest pain. She had delivered her first child 9 months before admission. Computed tomography showed a bulky mass in her left chest, and histopathological analysis revealed it to be dedifferentiated liposarcoma. We initiated doxorubicin chemotherapy, and the tumor mass reduced. After that, we performed vascular embolization along with chemotherapy, but tumor size did not reduce. On the 160th day of illness, the patient died. This is the first report of a primary diaphragmatic dedifferentiated liposarcoma diagnosed after delivery. Establishment of a regimen of chemotherapy for bulky unresectable liposarcoma is necessary.

Pulmonary Mucosa-associated Lymphoid Tissue Lymphoma with Spontaneous Regression after Computed Tomography-guided Needle Biopsy: A Case Report and Summary of 8 Reported Cases.

A 72-year-old woman was admitted to our hospital with a solitary right lung nodule. She had no symptoms and no abnormal physical findings except for bladder cancer. Tumor markers were mildly elevated but no other abnormal laboratory data were found. The nodule was diagnosed to be pulmonary mucosa-associated lymphoid tissue lymphoma on computed tomography-guided needle biopsy. Thereafter, she first underwent surgery for bladder cancer. The lung nodule was found to have slightly increased at three months and then disappeared at 15 months after the biopsy. The notable clinical course of this rare disease suggests the effectiveness of a non-interventional treatment strategy.

Phase II trial of weekly nab-paclitaxel for previously treated advanced non-small cell lung cancer: Kumamoto thoracic oncology study group (KTOSG) trial 1301.

OBJECTIVES: We performed an open-label, multicenter, single-arm phase II study (UMIN ID 000010532) to prospectively evaluate the efficacy and safety of nab-paclitaxel for previously treated patients with advanced non-small cell lung cancer (NSCLC). METHODS: Patients with advanced NSCLC who experienced failure of prior platinum-doublet chemotherapy received weekly nab-paclitaxel (100mg/m(2)) on days 1, 8, and 15 of a 21-day cycle until disease progression or the development of unacceptable toxicity. The primary end point of the study was objective response rate (ORR). RESULTS: Forty-one patients were enrolled between September 2013 and April 2015. The ORR was 31.7% (90% confidence interval, 19.3%-44.1%), which met the primary objective of the study. Median progression-free survival was 4.9 months (95% confidence interval, 2.4-7.4 months) and median overall survival was 13.0 (95% confidence interval, 8.0-18.0 months) months. The median number of treatment cycles was four (range, 1-17) over the entire study period, and the median dose intensity was 89.1mg/m(2) per week. Hematologic toxicities of grade 3 or 4 included neutropenia (19.5%) and leukopenia (17.1%), with no cases of febrile neutropenia being observed. Individual nonhematologic toxicities of grade 3 or higher occurred with a frequency of <5%. CONCLUSION: Weekly nab-paclitaxel was associated with acceptable toxicity and a favorable ORR in previously treated patients with advanced NSCLC. Our results justify the undertaking of a phase III trial comparing nab-paclitaxel with docetaxel in this patient population.

Elevated serum IgG4 levels in two cases of paragonimiasis.

Paragonimiasis is a parasitic pleuropulmonary infection caused by eating raw crustaceans and wild boar meat and this infection is endemic in Asia. We herein report two cases of pulmonary P aragonimus westermani infection associated with elevated levels of serum immunoglobulin (Ig) G4 and dense infiltration of IgG4-positive plasma cells in the lung lesions. Treatment with praziquantel resolved the pulmonary lesions and decreased the serum levels of IgG4. IgG4-related disease is a systemic disease occasionally involving the lungs and leads to increased serum levels of IgG4. Our findings suggest that P. westermani infection requires a differential diagnosis from IgG4-related diseases and the serum IgG4 level may be a potentially useful marker of P. westermani infection.

A Case of Biphasic Pulmonary Blastoma Treated with Carboplatin and Paclitaxel plus Bevacizumab.

Background. Pulmonary blastoma is a rare lung tumor similar to fetal lung tissues. Surgical resection at early stage is more curative than other treatments, but there is no standard treatment in unresectable cases. We show a case treated with carboplatin and paclitaxel plus bevacizumab. Case. A 68-year-old man received surgical resection and was diagnosed with biphasic pulmonary blastoma (pT3N0M0 stage IIB). Metastasis to the spleen was detected six weeks after the surgery. Carboplatin, paclitaxel, and bevacizumab were administered and showed an effect on the metastasis. Four courses of the chemotherapy were completed, but a metastasis was found and the metastatic tumor in the spleen was enlarged. After that, chemotherapy was not effective afterward and he died of the progression of biphasic pulmonary blastoma on the 292nd day of illness. Conclusion. In this case, chemotherapy with carboplatin and paclitaxel plus bevacizumab was temporarily efficacious for biphasic pulmonary blastoma.

Cisplatin-induced eosinophilic pneumonia.

A 67-year-old man suffering from esophageal cancer was admitted to our hospital complaining of dyspnea and hypoxemia. He had been treated with cisplatin, docetaxel, and fluorouracil combined with radiotherapy. Chest computed tomography revealed bilateral ground-glass opacity, and bronchoalveolar lavage fluid showed increased eosinophils. Two episodes of transient eosinophilia in peripheral blood were observed after serial administration of anticancer drugs before the admission, and drug-induced lymphocyte stimulation test to cisplatin was positive. Thus cisplatin-induced eosinophilic pneumonia was suspected, and corticosteroid was effectively administered. To our knowledge, this is the first reported case of cisplatin-induced eosinophilic pneumonia.

Insidious pulmonary fibrosis occurring at the hypoperfusion area in a patient with chronic pulmonary thromboembolism.

A 69-year-old woman who had been diagnosed with chronic pulmonary thromboembolism (CPTE) developed ground glass opacities in the right lung where perfusion scintigraphy showed defects of the bloodstream. Bronchoalveolar lavage fluid (BALF) showed that some macrophages had phagocytosed hemosiderin. Video-assisted thoracoscopic surgical biopsy revealed lung fibrosis, narrowing of the pulmonary artery and organization of many cholesterol granulomas. We hypothesized that hyperperfusion of the bronchial artery, which occurred to compensate for hypoperfusion of the pulmonary artery, induced alveolar hemorrhage following thrombolytic and anticoagulation treatments, and that the degraded products from blood cells induced the formation of lung fibrosis and cholesterol granulomas.

T cells of atopic asthmatics preferentially infiltrate into human bronchial xenografts in SCID mice.

T cells play an important role in the pathogenesis of bronchial asthma. However, it is not completely known how circulating lymphocytes infiltrate into the airways of asthmatic patients. Because SCID mice are unable to reject xenogenic transplants, many xenotransplant models using various human tissues have been developed. Therefore, to examine the interaction between bronchi and T lymphocytes of asthma, it may be possible to use the human bronchial xenograft and PBMC xenograft in SCID mice. We transplanted human bronchi into the subcutaneum of SCID mice and i.p. injected PBMCs that were obtained from patients with atopic asthma, atopic dermatitis and rheumatoid arthritis, and normal subjects (asthmatic, dermatitis, rheumatic, and normal huPBMC-SCID mice). There was no difference in the percentage of CD3-, CD4-, CD8-, CD25-, CD45RO-, CD103-, and cutaneous lymphocyte Ag-positive cells in PBMCs among the patients with asthma, dermatitis, rheumatoid arthritis, and normal subjects, and CD3-positive cells in peripheral blood of asthmatic, dermatitis, rheumatic, and normal huPBMC-SCID mice. The number of CD3-, CD4-, and CD8-positive cells in the xenografts of asthmatic huPBMC-SCID mice was higher than those of dermatitis, rheumatic, and normal huPBMC-SCID mice. IL-4 mRNA and IL-5 mRNA were significantly higher in the xenografts of asthmatic huPBMC-SCID mice than those in the xenografts of normal huPBMC-SCID mice, but there were no significant differences in the expressions of IL-2 mRNA or IFN-gamma mRNA between them. These findings suggest that T cells, especially Th2-type T cells, of asthmatics preferentially infiltrate into the human bronchi.