The first successful lung transplantation (LTx) was performed in 1983. Since then, more than 10000 LTx have been performed in the world, with approximately 1000 new cases each year in recent years. Lung transplantation is established as the ultimate treatment for end-stage pulmonary diseases. Clinical application of LTx was delayed in Japan because of difficulty in acceptance of brain death. The Japanese Brain Death Act (JBDA) for organ transplantation was enforced in October 1997. Now, LTx from a brain-dead cadaver donor (BDCD) becomes a clinical option for end-stage lung diseases in this country. Four LTx centers were selected and the registration of candidates for LTx started in August 1998. In total, up until May 2001, 51 patients had been registered on a waiting list. Patients' diseases for LTx in Japan are different from those in the US and Europe. So far, primary pulmonary hypertension (PPH; n = 23), idiopathic pulmonary fibrosis/interstitial pneumonia (IPF/IIP; n = 8), lymphangioleiomyomatosis (LAM; n = 7) and bronchiectasis (BE; n = 6) are the major indications for LTx in Japan. Fourteen patients (27%) have died while waiting for LTx and only eight patients (14%) have received lung allografts. The BDCD are quite precious and, thus far, only 13 donors have become available after enforcement of the JBDA. Although the average utilization of BDCD for LTx was reported to be only 10-20%, positive utility of marginal donors in Japan has led to a higher rate (five of 13; 36%). Six LTx were performed from five BDCD. These included five single LTx (LAM n = 3; IPF/IIP n = 2) and one bilateral LTx (PPH n = 1). Because there are few BDCD in Japan, living-donor lobar LTx (LDLTx) is thought to be the optimal choice for selected patients. Eight LDLTx (BE n = 2; bronchiolitis obliterans n = 2; IPF/IIP n = 2; LAM n = 1; and PPH n = 1) have been performed. All recipients who received a LTx in Japan are alive and doing well at present.

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Background: An increase in Japanese cedar pollen counts is the probable reason for the increase in the number of Japanese cedar hay fever patients. To determine whether local antigen exposure dose affects sensitization with cedar pollen, we compared serum levels of specific IgE antibody in rats exposed to higher and lower doses of cedar pollen antigen through the nose.
Methods: Serum levels of cedar pollen-specific IgE antibody was examined in Brown Norway rats exposed to a higher dose of (20 µg) Cry j I, a lower dose (2 µg) of Cry j I or no dose for 6 months. Serum levels of cedar pollen-specific IgE antibody were measured by reverse IgE-capture ELISA. The extent of local eosinophilia in the nasal, laryngeal and tracheal mucosa of rats exposed higher and lower doses of cedar pollen antigen and controls were observed microscopically.
Results: The mean serum levels of specific IgE antibody in rats exposed to the higher dose were significantly higher than those in rats exposed to the lower dose, and the mean levels in rats in the lower-dose group were significantly higher than in controls. The extent of eosinophilia in the nasal mucosa in the higher-dose group was significantly greater than in controls, but no significant differences between the lower-dose group and controls were found. The extent of eosinophilia in the laryngeal mucosa in the higher-dose group was significantly greater than that in the lower-dose group and in controls. Only a small degree of eosinophilia was observed in the trachea of all three groups.
Conclusions: Local exposure dose of the upper airway to cedar pollen may affect sensitization.

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Background: RANTES and eotaxin play an important role in the production of allergic inflammation of the airway through a chemotactic activity for eosinophils. Airway smooth muscle (ASM) cells are known to produce these cytokines in response to pro-inflammatory stimuli, such as tumor necrosis factor (TNF)-α; however, it has not been determined whether mechanical strain could induce cytokine production by ASM cells. In addition, in the present study we also examined the effect of inhalant corticosteroids, namely fluticasone propionate (FP) and budesonide (BUD), on RANTES and eotaxin production.
Methods: To clarify these issues, human ASM cells cultured on silicone culture rubber dishes that had been incubated with or without inhalant corticosteroids were stretched or compressed. The ASM cells were simultaneously stimulated with TNF-α. The concentration of RANTES and eotaxin in the culture supernatants was determined.
Results: The results showed that: (i) mechanical strain, including stretch and compression, stimulated ASM cells to produce RANTES and eotaxin; and (ii) FP and BUD inhibited mechanical strain-induced and TNF-α-stimulated RANTES and eotaxin production by ASM cells. These results indicate that mechanical strain is capable of inducing RANTES and eotaxin production by ASM cells and that inhalant corticosteroids effectively inhibit RANTES and eotaxin production by mechanical strain-loaded ASM cells, as well as by TNF-α-stimulated cells.
Conclusions: Mechanical strain and inflammatory stimuli are capable of inducing chemokine production; therefore, suppressing the contraction of, as well as chemokine production by, ASM cells is important for controlling the production and the progression of allergic inflammation.

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Background: Since the observation that Bacillus Calmette-Guérin (BCG) vaccination in children correlates with a decreased prevalence of asthma, several investigators have been attempting to reproduce this effect experimentally in mouse models of asthma. While these reports have agreed in some areas, uncertainty has remained as to the effect of BCG on IgE and asthmatic response in general. Furthermore, the effect of mycobacterial antigens on the early allergic response and the release of bronchoconstrictory mediators have not been examined. In the present study, we have aimed to more completely describe the effect of BCG and Mycobacterium vaccae on early and late allergic responses (EAR and LAR, respectively), airway hyperresponsiveness (AHR) and bronchoconstrictory mediators in the mouse model of allergic airway inflammation.
Methods: Using BALB/c mice sensitized to ovalbumin (OVA) and treated twice with either BCG or M. vaccae (1 × 10⁵ CFU, intranasally), we investigated airway resistance of both the EAR and LAR, AHR to methacholine, serum total and antigen-specific IgE, cysteinyl leukotrienes in bronchoalveolar lavage (BAL) fluid (10 min following challenge), a complete cell differential of the BAL (24 h post-challenge), BAL and serum cytokines and lung histology.
Results: Neither BCG nor M. vaccae were able to attenuate the EAR, yet both were able to abrogate the parameters used to evaluate the LAR. Interestingly, in neither case were serum or OVA-specific IgE levels reduced after treatment with mycobacterial antigens and type 1/type 2 T cell cytokine skewing, based on cytokine levels in BAL and serum, was incomplete.
Conclusions: These results have led us to conclude that the mycobacterial antigens elicit potential anti-asthmatic effects independent of changes in IgE levels. We speculate that mycobacteria likely directly or indirectly suppress eosinophil effector function via attenuation of type 2 T cell-mediated immune responses.

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Background: Total serum IgE may be increased in alcoholics. IgE synthesis depends on B cell activation by Th2-type cytokines. Serum sCD30 has been proposed as a marker of Th2 responses. The aim of the present study was to evaluate serum sCD30 levels in alcoholics and their relationship with serum IgE values.
Methods: Twenty-five active alcoholics and 18 healthy controls were included in the study. All subjects were non-atopic (asymptomatic from the allergologic point of view and Phadiatop^® (Phamacia & Upjohn Diagnostics AB, Uppsala, Sweden) negative). Serum IgE was measured by chemiluminescent enzyme immunoassay and serum sCD30 was assayed by ELISA.
Results: Total serum IgE was higher in alcoholics than in controls (median (range) for alcoholics and controls 59 (15.8-236) vs 24 (4-103) IU/mL, respectively; P = 0.003). Conversely, median serum sCD30 levels were lower in alcoholics than in controls (< 1 (< 1-144) vs 7.3 (< 1-83) U/mL, respectively; P = 0.02). Among the alcoholics, a negative correlation between serum IgE and sCD30 values was observed.
Conclusions: Increased serum IgE in non-atopic alcoholics is associated with low serum sCD30 concentrations. In so far as sCD30 is a marker of Th2 activation, total serum IgE elevation in alcoholics does not seem to be related to Th2 dominance.

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Background: To test the hypothesis that both daily activities and sleep quality may be mutually disturbed in elderly subjects with chronic obstructive pulmonary disease (COPD) or bronchial asthma (BA) and to determine factor(s) that relate to deterioration.
Methods: Elderly subjects with chronic airflow obstruction (group R; n = 60), consisting of COPD and BA, were compared with subjects without respiratory symptoms (group C; n = 53). Both daily activities and sleep quality were assessed by force-gravity (GF) measurement using an accelerometer.
Results: The night study showed that both total sleeping period and frequency of GF in group R were increased significantly compared with group C. Subjects with BA showed fewer movements differing from those in COPD subjects. The daytime study indicated that the frequency of GF was greater in group C than in group R, suggesting reduced daily activities in group R. Subjects with BA showed more movement than COPD subjects. Hypercapnia was a significant factor causing COPD subjects to move more frequently during sleep and a decrease in peak flow rate was a significant factor in the reduction of movement during the day in subjects with BA.
Conclusions: It is assumed that elderly subjects with COPD or bronchial asthma require a longer sleep period than subjects without respiratory symptoms because of the deterioration of sleep quality in the former group and the sleeping pattern differs between subjects with COPD and BA. Hypercapnia is considered a possible factor disturbing sleeping quality in COPD, whereas decreased peak expiratory flow rate is a factor reducing daytime activities in subjects with BA.

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Background: The aim of the present study was to assess the effect of atopy and regular therapy for asthma on exhaled nitric oxide (eNO).
Methods: Exhaled NO was measured using a chemiluminescence analyzer during slow expiration in 83 children, aged 5-7 years, after hospitalization for wheezing in infancy. The mean (±SD) age of the subjects was 7.2 ± 0.7 years, 28% were girls and 42% were atopic. A total of 31 children (37%) had asthma with regular medication: 20 were taking cromones, and 11 were taking inhaled steroids.
Results: In the asthma group, the median concentration of eNO was 14.9 p.p.b. (range 3.5-56.1 p.p.b.) in atopics and 7.3 p.p.b. (range 5.1-15.6 p.p.b.) in non-atopics (P < 0.01). The levels for atopic children on cromones tended to be higher than for those on inhaled steroids; however, the difference did not reach statistical significance.
Conclusion: We conclude that eNO concentrations associate significantly with atopic asthma.

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Bronchial asthma has been recognized as an inflammatory disorder in this past decade. This leads to an assumption that perfect control of inflammatory cells may cure this disease. However, herein we report on an asthmatic whose airway hyperresponsiveness (AHR) did not change after bone marrow transplantation (BMT). The concentrations of acetylcholine to produce a 20% fall in forced expiratory volume in 1 s 15 days before and 98 days after BMT were 900 and 480 µg/mL, respectively. Asthma treatment with beclomethasone dipropionate and theophylline was continued before and after BMT and a conventional supporting therapy for BMT with cyclosporine A and methylprednisolone, followed by oral administration of tacrolimus hydrate alone inhibited graft-versus-host disease. Plasma interleukin (IL)-4, IL-5 and IgE, but not interferon-γ, levels decreased after BMT. Note that the second measurement of airway sensitivity was performed under systemic administration of tacrolimus. The presented case suggests that replacement of bone marrow-derived inflammatory cells is not enough to reverse once-established AHR. Hence, AHR and airway inflammation may develop independently in some part, but both need to be present for asthma to be present in this asthmatic.

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