Biomedical subjects

Koichiro Matsumoto

Publications and source records attributed to Koichiro Matsumoto.

18 recordsLinked to original sources

PubMed2006

Overexpression of B7-H1 (PD-L1) significantly associates with tumor grade and postoperative prognosis in human urothelial cancers.

PURPOSE: The programmed death-1 (PD-1)/B7-H1 (also called PD-L1) pathway negatively regulates T cell activation and has been suggested to play an important role in regulating antitumor host immunity. To investigate the clinical significance of B7-H1 expression to the tumor grade and postoperative prognosis of patients with urothelial cancer, we analyzed the relationship between B7-H1 expression and various clinicopathological features and postoperative prognosis. EXPERIMENTAL DESIGN: Sixty-five urothelial cancer cases were examined. B7-H1 expression in tumors and the numbers and phenotypes of tumor-infiltrating lymphocytes were evaluated by immunohistochemistry and flow cytometry. RESULTS: A substantial expression of B7-H1 was observed in all urothelial cancers investigated. Tumor specimens from patients with higher WHO grade or primary tumor classifications showed significantly higher percentages of tumor-associated B7-H1. Tumor-associated B7-H1 expression was significantly associated with a high frequency of postoperative recurrence and poor survival rate. Furthermore, multivariate analysis indicated that tumor-associated B7-H1 was more significant prognostic factor than WHO grade. CONCLUSIONS: Our results demonstrate that the aberrant expression of B7-H1 in urothelial cancer is associated with aggressive tumors, suggesting a regulatory role of tumor-associated B7-H1 in antitumor immunity. Therefore, the manipulation of tumor-associated B7-H1 may become a beneficial target for immunotherapy in human urothelial cancer.

Antigens, CD↗

PubMed2006

A pregnant woman with complications of lymphangioleiomyomatosis and idiopathic thrombocytopenic purpura.

A pregnant 26-year-old woman developed hemosputum, dyspnea and pneumothorax. Lymphangioleiomyomatosis was suspected based on multiple cystic lesions on chest computed tomography. Additionally, moderate thrombocytopenia occurred during the last trimester. Hyperplasia of megakaryocytes in a bone marrow specimen and a high serum titer of platelet-associated IgG led to a diagnosis of idiopathic thrombocytopenic purpura. High-dose intravenous gammaglobulin promptly restored her platelet count, and the patient successfully gave birth to a healthy baby by cesarean section. After delivery, lymphangioleiomyomatosis was diagnosed by lung biopsy that was obtained during a video-assisted thoracoscopic abscission for recurrent pneumothorax. Underlying lymphangioleiomyomatosis and idiopathic thrombocytopenic purpura may be obviated by pregnancy.

Adult↗

PubMed2006

Effects of salmeterol in patients with persistent asthma receiving inhaled corticosteroid plus theophylline.

BACKGROUND: Patients with severe asthma require multiple therapies to improve lung function and reduce symptoms. The use of long-acting inhaled beta(2)-agonists plus theophylline in addition to high doses of inhaled corticosteroids (ICSs) for the treatment of severe asthma has not been extensively studied. OBJECTIVE: The purpose of this study was to investigate the efficacy and safety of salmeterol combined with high-dose ICSs plus theophylline in severe asthma. METHODS: We undertook a randomized, placebo-controlled, crossover study to compare the effect of a single dose of inhaled salmeterol (50 microg) or a placebo in patients with severe asthma whose conditions were not being adequately controlled by therapies with high-dose ICSs plus oral theophylline with or without leukotriene receptor antagonists. RESULTS: Twenty patients took part in the trial. Compared with the placebo, the inhalation of salmeterol significantly increased the FEV(1). Even in the 9 patients treated with high-dose ICSs plus theophylline plus a leukotriene receptor antagonist, the FEV(1) increased significantly more after salmeterol than after the placebo. CONCLUSION: Patients with severe asthma receiving high-dose ICSs plus theophylline may benefit from the addition of salmeterol.

Administration, Inhalation↗

PubMed2006

Niflumic acid suppresses interleukin-13-induced asthma phenotypes.

RATIONALE: Chloride channels have been implicated in the regulation of mucus production in epithelial cells. Expression of hCLCA1, a calcium-activated chloride channel, has been reported to be increased in the airway epithelium of patients with asthma. Interleukin (IL)-13 induces the cardinal features of bronchial asthma, and glucocorticoids are not sufficient to suppress IL-13-induced airway hyperresponsiveness or goblet cell hyperplasia. OBJECTIVES: We studied the effects of chloride channel inhibitors in IL-13-induced asthma. METHODS: The effects of niflumic acid (NA), a relatively specific blocker of calcium-activated chloride channel (CLCA), on goblet cell hyperplasia, eosinophil accumulation, and airway hyperresponsiveness were evaluated after IL-13 instillation into the airways. Because IL-13-dependent features rely on JAK/STAT6 signaling, the effect of NA on phosphorylation of JAK2 and STAT6 after IL-13 stimulation was examined in airway epithelial cells in vitro. The expression of the mCLCA family in mouse lung after IL-13 local administration in vivo was analyzed using reverse transcription-polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS: Treatment with NA inhibited not only IL-13-induced goblet cell hyperplasia but also airway hyperresponsiveness and eosinophilic infiltration. NA suppressed the eotaxin levels in bronchoalveolar lavage fluids and overexpression of the MUC5AC gene, a marker of goblet cell hyperplasia, in the lung after IL-13 instillation. NA suppressed JAK2 activation, STAT6 activation, and eotaxin expression in epithelial cells. The expression of mCLCA3 (mouse homolog hCLCA1), but not that of other CLCA family members, was up-regulated by IL-13. CONCLUSIONS: These findings suggest that a chloride channel inhibitor can control IL-13-mediated airway features at least by suppressing JAK/STAT6 activation.

Animals↗

PubMed2005

Exacerbation of experimental allergic asthma by augmented Th2 responses in WSX-1-deficient mice.

WSX-1 (IL-27R) is a class I cytokine receptor with homology to gp130 and IL-12 receptors and is typically expressed on CD4+ T lymphocytes. Although previous reports have clarified that IL-27/WSX-1 signaling plays critical roles in both Th1 differentiation and attenuation of cell activation and proinflammatory cytokine production during some bacterial or protozoan infections, little is known about the importance of WSX-1 in cytokine-mediated diseases of allergic origin. To this aim, we took advantage of WSX-1-deficient (WSX-1(-/-)) mice and induced experimental asthma, in which Th2 cytokines are central modulators of the pathology. OVA-challenged WSX-1(-/-) mice showed marked enhancement of airway responsiveness with goblet cell hyperplasia, pulmonary eosinophil infiltration, and increased serum IgE levels compared with wild-type mice. Production of Th2 cytokines, which are largely responsible for the pathogenesis of asthma, was augmented in the lung or in the culture supernatants of peribronchial lymph node CD4+ T cells from WSX-1(-/-) mice compared with those from wild-type mice. Surprisingly, IFN-gamma production was also enhanced in WSX-1(-/-) mice, albeit at a low concentration. The cytokine overproduction, thus, seems independent from the Th1-promoting property of WSX-1. These results demonstrated that IL-27/WSX-1 also plays an important role in the down-regulation of airway hyper-reactivity and lung inflammation during the development of allergic asthma through its suppressive effect on cytokine production.

Animals↗

PubMed2005

Expression of B7-H1 and B7-DC on the airway epithelium is enhanced by double-stranded RNA.

Viral infection in the airway provokes various immune responses, including Th1 and Th2 responses, which are partly initiated by double-stranded RNA (dsRNA), a viral product for its replication. B7-H1 (PD-L1) and B7-DC (PD-L2) are B7-family molecules that bind to programmed death-1 (PD-1) on lymphocytes and are implicated in peripheral tolerance. We investigated the effect of dsRNA on the expression of B7-H1 and B7-DC on airway epithelial cell lines. B7-H1 and B7-DC were constitutively expressed on the cells, and their expression was profoundly upregulated by stimulation with an analog of viral dsRNA, polyinosinic-polycytidylic acid. B7-H1 and B7-DC were also upregulated by stimulation with IFN-gamma, IL-13, and the supernatant from T cell clones. A relatively high concentration of dexamethasone (1 microM) was required to suppress the upregulation of B7-H1 or B7-DC. These results suggest that epithelial B7-H1 and B7-DC play a role in virus-associated immune responses in the airways.

Antigens, CD↗

PubMed2005

Spred-1 negatively regulates allergen-induced airway eosinophilia and hyperresponsiveness.

T helper 2 cytokines, including interleukin (IL)-4, IL-5, and IL-13, play a critical role in allergic asthma. These cytokines transmit signals through the Janus kinase/signal transducer and activator of transcription (STAT) and the Ras-extracellular signal-regulated kinase (ERK) signaling pathways. Although the suppressor of cytokine signaling (SOCS) family proteins have been shown to regulate the STAT pathway, the mechanism regulating the ERK pathway has not been clarified. The Sprouty-related Ena/VASP homology 1-domain-containing protein (Spred)-1 has recently been identified as a negative regulator of growth factor-mediated, Ras-dependent ERK activation. Here, using Spred-1-deficient mice, we demonstrated that Spred-1 negatively regulates allergen-induced airway eosinophilia and hyperresponsiveness, without affecting helper T cell differentiation. Biochemical assays indicate that Spred-1 suppresses IL-5-dependent cell proliferation and ERK activation. These data indicate that Spred-1 negatively controls eosinophil numbers and functions by modulating IL-5 signaling in allergic asthma.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Different roles of interleukin-10 in onset and resolution of asthmatic responses in allergen-challenged mice.

OBJECTIVE: Although interleukin (IL)-10 is an immunoregulatory cytokine produced by various cells including T cells, its precise role in asthma remains uncertain. The aim of this study was to investigate the role of IL-10 in experimental asthma using ovalbumin (OVA)-sensitized mice. METHODOLOGY: Mice were challenged with OVA aerosol, and airway responsiveness and inflammation were measured. OVA-specific IL-10-producing CD4+ T cells were counted from lung cells collected by enzymatic digestion and stimulated ex vivo with OVA. The effects of an anti-IL-10 antibody on airway responsiveness and inflammation were also evaluated. RESULTS: The OVA challenge caused airway hyperresponsiveness and eosinophilic inflammation. A significant increase in IL-10-producing CD4+ T cells was observed, mainly in the CD45RB(low) subset, for several days after the OVA challenge. Anti-IL-10 antibody treatment before the OVA challenge did not affect eosinophilic inflammation but significantly inhibited airway hyperresponsiveness 24 h after the OVA challenge. However, anti-IL-10 antibody treatment just before the last OVA challenge significantly attenuated the resolution of eosinophilic inflammation without affecting airway responsiveness 2 weeks after the OVA challenge. CONCLUSIONS: Intrinsic IL-10 may have a distinct role in the early and late phases of asthmatic responses. In the early phase, IL-10 induces airway hyperresponsiveness, while in the late phase IL-10 contributes to the resolution of eosinophilic inflammation.

Allergens↗

PubMed2004

Activation of PI3K-Akt pathway mediates antiapoptotic effects of beta-adrenergic agonist in airway eosinophils.

beta-Adrenoceptor agonists reportedly decrease spontaneous apoptosis of peripheral blood eosinophils; however, its signaling pathway is unknown. Survival signals can be elicited by the activation of phosphatidylinositol 3-kinase (PI3K) and Akt, both of which are known to be potent regulators of apoptosis, and Akt in turn inactivates Forkhead transcription factors, including FKHR (Forkhead in rhabdomyosarcoma). We have investigated the effect of beta-agonists on apoptosis of local eosinophils isolated from the airways and the involvement of PI3K, Akt, and FKHR in its survival signal. Eosinophils obtained from immunized mice by bronchoalveolar lavage after allergen provocation underwent apoptosis in a time-dependent manner. Incubation of eosinophils with isoproterenol or formoterol dose-dependently inhibited both spontaneous eosinophil apoptosis and apoptosis induced by Fas receptor activation. Incubation with cAMP or forskolin also inhibited eosinophil apoptosis. The PI3K inhibitors wortmannin and LY-294002 and an Akt inhibitor, 1-L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate, but not a mitogen-activated protein kinase kinase inhibitor PD-98059, blocked isoproterenol-mediated eosinophil survival. Wortmannin also inhibited cAMP-mediated eosinophil survival. Isoproterenol rapidly induced phosphorylation of Akt and FKHR in eosinophils in a PI3K-dependent manner. These findings indicate that the PI3K-Akt-FKHR pathway conveys a critical survival signal induced by beta-agonists in airway eosinophils.

Adrenergic beta-Agonists↗

PubMed2004

Decrease of interleukin-10-producing T cells in the peripheral blood of severe unstable atopic asthmatics.

BACKGROUND: Although IL-10 is known as an immunoregulatory cytokine produced by various cells including T cells, its basic profile in atopic asthma remains uncertain. OBJECTIVE: The profiles of IL-10 production in circulating CD4+ T cells of atopic asthmatics were investigated with respect to clinical severity. METHODS: Forty atopic asthmatics were divided into three groups: mild, and severe but stable and severe unstable asthmatics. Eosinophils were counted in the peripheral blood and sputum, and exhaled nitric oxide was assessed. PBMCs were stimulated with or without anti-CD3 and anti-CD28 antibodies and then processed for detecting IL-10-producing CD4+ cells using flow cytometry. RESULTS: There was no difference in the eosinophil count in blood or sputum and in nitric oxide level among the three groups. IL-10-producing CD4+ cells were mainly detected in a CD45RO+ memory population. The frequency of IL-10-producing cells after stimulation was significantly lower in the severe unstable group compared to the mild group. In addition, the frequency of IL-10-producing cells in the severe unstable group was significantly lower than that in the severe stable group despite the fact that both groups received similar treatments with high-dose inhaled corticosteroids. The IL-10 production of CD4+CD45RO+ cells in response to dexamethasone did not differ among the three groups. CONCLUSIONS: IL-10-producing CD4+CD45RO+ cells in the peripheral blood are decreased in severe unstable asthmatics, which is not explained by the effect of high-dose inhaled corticosteroid medication.

Adult↗

PubMed2004

B7-DC regulates asthmatic response by an IFN-gamma-dependent mechanism.

B7-H1 (PD-L1) and B7-DC (PD-L2) are the ligands for programmed death-1 (PD-1), which is a member of the CD28/CTLA-4 family and has been implicated in peripheral tolerance. We investigated the roles of B7-H1 and B7-DC in a murine OVA-induced allergic asthma model. B7-H1 was constitutively expressed on dendritic cells, macrophages, B cells, and T cells in the lungs of naive mice, and its expression could be dramatically increased after allergen challenge. In contrast, B7-DC expression was scarcely expressed on dendritic cells in naive mice, but was up-regulated after allergen challenge, although the up-regulation of B7-DC expression on macrophages was minimal. Treatment of mice with anti-B7-DC mAb at the time of allergen challenge, but not at the time of sensitization, significantly increased their airway hyper-reactivity and eosinophilia. Such treatment also resulted in the increased production of IL-5 and IL-13, and decreased IFN-gamma production in the lungs and draining lymph node cells. These changes were diminished when mice were depleted of IFN-gamma by anti-IFN-gamma mAb pretreatment. Interestingly, treatment with anti-B7-H1 or anti-PD-1 mAb did not significantly affect the asthmatic response. These results suggest a unique role for B7-DC in the regulation of asthmatic response through an IFN-gamma-dependent, but PD-1-independent, mechanism.

Allergens↗

PubMed2004

[A case of relapsing polychondritis successfully assessed for airway diameters under application of bi-level positive airway pressure (bilevel PAP)].

A 52-year-old man was admitted to our department because of hypercapnic respiratory failure. His illness had begun with scleritis 5 years before, followed by swelling of the fingers and auricular cartilages and saddle nose 3 years before, when a clinical diagnosis of relapsing polychondritis was made. His chest CT after intubation revealed diffuse airway narrowing with complete collapse of both main bronchi on expiration. Though his clinical status was stabilized after initiation of mechanical ventilation and pulse-dose corticosteroid treatment, he was difficult to wean from the ventilator with a conventional on-off trial. We therefore assessed the diameters of the central airways using dynamic CT under application of bilevel PAP, which confirmed an improvement in airway patency. He was then successfully weaned from artificial ventilation using bilevel PAP, initially through tracheotomy and subsequently via a nasal mask. To our knowledge, this is the first report that confirms the advantage of bilevel PAP objectively for a patient with labile airways.

Bronchi↗

PubMed2003

SOCS-3 regulates onset and maintenance of T(H)2-mediated allergic responses.

Members of the suppressor of cytokine signaling (SOCS) family are involved in the pathogenesis of many inflammatory diseases. SOCS-3 is predominantly expressed in T-helper type 2 (T(H)2) cells, but its role in T(H)2-related allergic diseases remains to be investigated. In this study we provide a strong correlation between SOCS-3 expression and the pathology of asthma and atopic dermatitis, as well as serum IgE levels in allergic human patients. SOCS-3 transgenic mice showed increased T(H)2 responses and multiple pathological features characteristic of asthma in an airway hypersensitivity model system. In contrast, dominant-negative mutant SOCS-3 transgenic mice, as well as mice with a heterozygous deletion of Socs3, had decreased T(H)2 development. These data indicate that SOCS-3 has an important role in regulating the onset and maintenance of T(H)2-mediated allergic immune disease, and suggest that SOCS-3 may be a new therapeutic target for the development of antiallergic drugs.

Animals↗

PubMed2003

Differential regulation by glucocorticoid of interleukin-13-induced eosinophilia, hyperresponsiveness, and goblet cell hyperplasia in mouse airways.

Interleukin (IL)-13 induces important features of bronchial asthma such as eosinophilic infiltration, airway hyperresponsiveness (AHR), and mucus hypersecretion. Although glucocorticoids suppress airway inflammation and remain the most effective therapy for asthma, the effects of glucocorticoids on the IL-13-dependent features are unknown. We studied the effects of dexamethasone on eotaxin production, eosinophil accumulation, goblet cell hyperplasia, and AHR after IL-13 administration into the airways of mice in vivo. MUC5AC gene expression, a marker of goblet cell hyperplasia, was also analyzed. IL-13 alone dose dependently induced AHR. Treatment with dexamethasone inhibited eotaxin expression and completely abolished eosinophil accumulation, but it did not affect AHR, MUC5AC overexpression, or goblet cell hyperplasia induced by IL-13. The effects of tumor necrosis factor-alpha on IL-13-induced AHR were also examined. Tumor necrosis factor-alpha did not affect AHR despite marked enhancement of eosinophil infiltration in IL-13-treated mice. These findings suggest that glucocorticoid is not sufficient to suppress IL-13-induced AHR or goblet cell hyperplasia and that eotaxin expression and eosinophilic inflammation do not have a causal relationship to the induction of AHR or goblet cell hyperplasia by IL-13. Control of steroid-resistant features induced by IL-13, including AHR and mucus production, may provide new therapeutic modalities for asthma.

Animals↗

PubMed2002

Effect of interferon-gamma on allergic airway responses in interferon-gamma-deficient mice.

Interferon (IFN)-gamma reduces airway responses after allergen challenge in mice. The mechanisms of this effect are not clear. These studies investigate whether IFN-gamma can reverse prolonged airway responses after allergen challenge in IFN-gamma-deficient (IFN-gammaKO) mice. Sensitized mice (IFN-gammaKO and wild-type [WT]) were challenged with ovalbumin. Airway responsiveness, eosinophils in bronchoalveolar lavage fluid, and lung lymphocyte subsets (CD4(+) and CD8(+)) were measured 24 hours and 8 weeks after challenge. In further experiments, we treated IFN-gammaKO mice with recombinant IFN-gamma starting 4 weeks after the challenge for 1 week or 4 weeks. Airway responsiveness, bronchoalveolar lavage eosinophils, and lung CD4(+) cells were increased 8 weeks after challenge in IFN-gammaKO but not WT mice. IFN-gamma treatment returned lung CD4(+) cell numbers to values obtained in unchallenged mice. One week of IFN-gamma treatment also returned airway responsiveness to baseline levels; however, 4-week treatment with IFN-gamma failed to decrease airway responsiveness below levels observed in untreated animals. This suggests that IFN-gamma plays an essential role in reversing allergen-induced airway inflammation and hyperresponsiveness and that it may have dual actions on the latter. Observations that IFN-gamma reverses airway responses, even when administered after challenge, suggests that IFN-gamma treatment could control allergic disease, including asthma.

Airway Obstruction↗

PubMed2002

Pathogenesis of murine experimental allergic rhinitis: a study of local and systemic consequences of IL-5 deficiency.

Recent studies have demonstrated an important role for IL-5-dependent bone marrow eosinophil progenitors in allergic inflammation. However, studies using anti-IL-5 mAbs in human asthmatics have failed to suppress lower airway hyperresponsiveness despite suppression of eosinophilia; therefore, it is critical to examine the role of IL-5 and bone marrow responses in the pathogenesis of allergic airway disease. To do this, we studied the effects of IL-5 deficiency (IL-5(-/-)) on bone marrow function as well as clinical and local events, using an established experimental murine model of allergic rhinitis. Age-matched IL-5(+/+) and IL-5(-/-) BALB/c mice were sensitized to OVA followed by 2 wk of daily OVA intranasal challenge. IL-5(-/-) OVA-sensitized mice had significantly higher nasal mucosal CD4(+) cells and basophilic cell counts as well as nasal symptoms and histamine hyperresponsiveness than the nonsensitized group; however, there was no eosinophilia in either nasal mucosa or bone marrow; significantly lower numbers of eosinophil/basophil CFU and maturing CFU eosinophils in the presence of recombinant mouse IL-5 in vitro; and significantly lower expression of IL-5Ralpha on bone marrow CD34(+)CD45(+) progenitor cells in IL-5(-/-) mice. These findings suggest that IL-5 is required for normal bone marrow eosinophilopoiesis, in response to specific Ag sensitization, during the development of experimental allergic rhinitis. However, the results also suggest that suppression of the IL-5-eosinophil pathway in this model of allergic rhinitis may not completely suppress clinical symptoms or nasal histamine hyperresponsiveness, because of the existence of other cytokine-progenitor pathways that may induce and maintain the presence of other inflammatory cell populations.

Animals↗

PubMed2002

IL-10 production in circulating T cells differs between allergen-induced isolated early and dual asthmatic responders.

BACKGROUND: IL-10 is an anti-inflammatory cytokine released from various cells, including T cells. The role of IL-10 in asthma pathogenesis remains uncertain. Allergen inhalation by atopic asthmatic subjects results in 2 bronchoconstrictor phenotypes: isolated early response and dual response. Persistence of allergen-induced airway inflammation is a feature of dual responders. OBJECTIVES: The kinetics of IL-10 production in circulating T cells were investigated to examine a potential role of IL-10 in allergen-induced responses and airway inflammation. METHODS: Fourteen subjects with mild asthma (7 isolated early and 7 dual responders) were challenged with allergen. PBMCs taken before and 24 hours after allergen challenge were processed for intracellular IL-10 staining with fluorescent-conjugated anti-IL-10 antibody. The frequency of IL-10-producing cells was assessed for CD4(+) and CD8(+) T-cell subsets by using flow cytometry. RESULTS: Before allergen administration, the frequency of IL-10-producing CD4(+) cells was significantly higher in dual than in isolated early responders. IL-10-producing CD4(+) cells significantly increased after allergen in early responders, whereas IL-10-producing CD4(+) cells significantly decreased in dual responders. Simultaneous assessments of IL-5-producing T cells did not show any differences between each group before or after allergen administration. CONCLUSIONS: These results suggest that the contrasting profiles of IL-10 production may be associated with the different time course of allergen-induced airway inflammation between allergen-induced early and dual responders.

Administration, Inhalation↗

PubMed2002

[Clinical features of five cases of pulmonary Langerhans' cell histiocytosis].

We reviewed the clinical features of 5 cases of Langerhans' cell histiocytosis that had been referred because of pulmonary lesions. The most frequent symptom was persistent dry cough. Chest radiographs showed bilateral, symmetric reticulonodular infiltrates and accompanying cystic changes with an upper-field predominance. Pulmonary function testing (PFT) revealed moderate restrictive impairment in 3 patients. All the above features were in accordance with previous reports. The incidence of complications was, however, higher in the present cases than reported in the literature. Four cases were complicated with diabetes insipidus (DI), which caused polydipsia and polyuria on the initial presentation and was subsequently managed with intranasal desmopressin. In 4 cases, bone lesions were detected. A bone scintigram at 99mTc proved to be useful for surveillance. All patients had been followed up closely for longer than 2 years (median duration 2.8 years). Their clinical courses were generally stable without apparent decline in PFT, except that one patient with a psychiatric problem died from hypernatremia due to misuse of desmopressin. Immunosuppressive agents were given in only 2 patients including the one who died. Four transbronchial biopsies (TBB) were performed in 4 cases and at least 3 specimens were sampled from each. Histological diagnoses were made from TBB specimens in 3 patients, while the remaining 2 patients underwent an open lung biopsy. We conclude that TBB is acceptable as an initial diagnostic attempt. Multiple sampling may also contribute to preferable yield. Regarding patient management, we suggest that DI and bone lesions should be sought extensively as their incidence may be much higher than previously estimated.

Adolescent↗