Effects of smoking cessation on gastric emptying in smokers.

BACKGROUND: Smoking cessation can lead to changes in appetite and weight gain in some patients; thus, smoking cessation may alter gastrointestinal motility. Effects of smoking cessation on gastric emptying in smokers have not been established. AIM: This study sought to determine how smoking cessation affects gastric emptying in smokers. METHODS: Participant group comprised 53 habitual smokers and 12 healthy nonsmokers. Habitual smokers were treated for 2 months with transdermal nicotine patches. Gastric emptying was studied using C acetate breath tests at the beginning of the study, and at 1 week and 9 weeks after cessation of patch use. Maximal CO2 excretion time (Tmax), CO2 excretion half-life (T1/2), and parameters beta and kappa, representing initial and subsequent gastric-emptying phases, respectively, were determined using conventional formulae. RESULTS: Before smoking cessation, Tmax was reached significantly later in smokers (0.94+/-0.3 h, P=0.014) than in controls (0.89+/-0.1 h). At 1 week after the end of treatment, Tmax was significantly decreased (from 1.05+/-0.32 h to 0.72+/-0.64 h, P=0.003). T1/2 also tended to decrease, but not significantly. Although beta was decreased significantly (from 2.46+/-0.40 to 2.17+/-0.58, P=0.022), kappa was unchanged. However, by 9 weeks after the end of treatment, Tmax (1.28+/-0.69 h) had increased to levels seen before treatment. CONCLUSIONS: Smoking cessation temporarily accelerates gastric emptying, and decreases in beta suggest that initial-phase gastric emptying accelerates after smoking cessation. The temporary acceleration of gastric emptying after smoking cessation may be involved in the temporary increase in appetite and weight gain seen after smoking cessation.

Low expression of T-cell co-stimulatory molecules in bone marrow-derived dendritic cells in a mouse model of chronic respiratory infection with Pseudomonas aeruginosa.

Pseudomonas (P.) aeruginosa frequently colonizes the respiratory tract of patients with chronic respiratory tract infections such as diffuse panbronchiolitis (DPB). The number of dendritic cells (DCs) that play a central role in immune functions as antigen-presenting cells is reportedly increased in the bronchiolar tissues of patients with DPB. However, the functions of DCs in chronic P. aeruginosa respiratory tract infection have not been defined. Here, we assessed the functions of DCs and the effect of macrolide antibiotics that are therapeutic agents for DPB, in a murine model of DPB caused by P. aeruginosa. Mice were intubated with either P. aeruginosa- or saline-precoated tubes for 80 days. Thereafter, the expression of T-cell co-stimulatory molecules (CD40, CD80, and CD86) and cytokine secretion (interleukin (IL)-10, IL-6, IL-12p40, and tumor necrosis factor (TNF)-alpha) on bone marrow-derived DCs stimulated by lipopolysaccharide were examined by flow cytometry and enzyme-linked immunosorbent assays. The expression of co-stimulatory molecules was significantly decreased in mice infected with P. aeruginosa compared to the saline-treated control mice, but production of these cytokines did not significantly differ between the two groups. Pretreatment with clarithromycin ex vivo decreased CD40 expression on DCs obtained from P. aeruginosa-infected mice and also decreased the production of IL-6, IL-12p40 and TNF-alpha by DCs. These findings suggest that chronic P. aeruginosa infection alters DC functions and that macrolides function as anti-inflammatory agents by modulating the functions of DCs in chronic P. aeruginosa infection.

[Three cases of isocyanate-induced hypersensitivity pneumonitis with different HRCT findings].

We reported 3 cases of hypersensitivity pneumonitis who had been exposed to polyurethane material containing diphenylmethane diisocyanate (MDI) for 1-12 weeks. They had cough, fever and dyspnea before admission. All 3 cases were diagnosed immunologically using anti-MDI antibodies. Chest HRCT findings of the 3 cases were different. Case 1 showed an organizing pneumonia (OP) pattern : patchy peripheral consolidation with air bronchogram and ground-glass opacities (GGO), and case 2 showed a nonspecific interstitial pneumonia (NSIP) pattern : consolidation and reticular shadows in both lower lobes. In addition, case 3 showed a hypersensitivity pneumonitis (HP) pattern : centrilobular GGO and diffuse granular shadows. All cases were successfully treated by corticosteroids alone. This suggests that different amounts of inhaled antigen can cause different HRCT findings.

Elevated levels of tenascin-C in patients with cryptogenic organizing pneumonia.

OBJECTIVE: Idiopathic interstitial pneumonias (IIPs) comprises a group of diffuse parenchymal lung diseases of unknown etiology with varying degrees of inflammation and fibrosis including cryptogenic organizing pneumonia (COP), idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP). Tenascin-C is an extracellular matrix molecule that is expressed during wound healing in various tissues. The present study was aimed to investigate the role of tenascin-C in the pathogenesis of IIPs. METHODS: We used enzyme-linked immunosorbent assays to measure levels of tenascin-C in serum and bronchoalveolar lavage fluid (BALF) from 17 patients with IPF, 12 with NSIP, 15 with COP and from 23 healthy individuals. RESULTS: Serum levels of tenascin-C were significantly elevated in patients with COP compared with those in all other participants, whereas those in patients with IPF and NSIP were not significantly elevated compared with healthy individuals. The levels of tenascin-C in BALF from patients with COP and NSIP were significantly higher than those of healthy individuals. In addition, serum tenascin-C was significantly correlated with levels of serum C-reactive protein, which is a serum acute phase protein. CONCLUSION: Systemic inflammation in the lung with IIPs might be associated with tenascin-C. These results suggest that tenascin-C is responsible for the pathogenesis of IIPs especially via inflammation, and that it might serve as a serum marker of COP.

[Two cases of pleomorphic carcinoma with severe systemic inflammation].

We report two cases of pleomorphic carcinoma with fever and severe inflammatory reaction. In case 1, an abnormal mass shadow was found on the chest X-ray film of a 63-year-old man with bloody sputum. After right upper lobectomy, the tumor was diagnosed as pleomorphic carcinoma. About 7 months after surgical operation, he had fever and chest pain. Although his test results showed leukocytosis and his elevated serum CRP level indicated some infection, there were no signs of bacterial or fungal infection. Further examination revealed metases of lung cancer in the left adrenal gland, mediastinal and iliac lymph nodes. Serological study revealed elevated level of G-CSF, likely due to G-CSF producing metastatic tumors. In case 2, a 77-year-old man presented with continuous high fever. Examinations revealed elevated serum CRP level and multiple nodular shadows and enlarged supraclavicular and mediastinal lymph nodes on the chest CT, suggesting some infectious, connective tissue, or lymphoproliferative diseases. He was finally found to have pleomorphic carcinoma of the lung by histological examination of lymph nodes. The continuous high fever seemed to be a tumor-related fever, because it rapidly disappeared after administration of naproxen.

Clinical differences between interstitial lung disease associated with clinically amyopathic dermatomyositis and classic dermatomyositis.

BACKGROUND: Interstitial lung disease (ILD) associated with clinically amyopathic dermatomyositis (CADM) is a potentially fatal condition in which the clinical features are not well understood. The aim of the present study was to clarify the differences in clinical characteristics and prognosis of patients with ILD associated with CADM (CADM-ILD) and classic dermatomyositis associated with ILD (DM-ILD). METHODS: We retrospectively studied consecutive patients with CADM-ILD and classic DM-ILD who were hospitalized between 2001 and 2007 at Nagasaki University Hospital. The study group consisted of 11 patients with CADM-ILD and 16 patients with classic DM-ILD. We compared the clinical features and prognosis between the two forms. RESULTS: The Pao(2)/Fio(2) ratio was significantly lower in patients with CADM-ILD than in patients with classic DM-ILD. The lymphocyte subsets ratio in the BAL fluid of patients with CADM-ILD was significantly higher than the corresponding ratio in patients with classic DM-ILD. ILD is classified as acute or chronic, and the acute subtype was more common in patients with CADM-ILD than in those with classic DM-ILD. The mortality rate for patients with CADM-ILD (45%) was much higher than that for patients with classic DM-ILD (6%), and all of the CADM deaths occurred in the group of patients with acute CADM-ILD. CONCLUSION: Our data suggest that the higher prevalence of the acute subtype of ILD in patients with CADM results in a higher mortality rate for patients with CADM-ILD.

Different effects of telithromycin on MUC5AC production induced by human neutrophil peptide-1 or lipopolysaccharide in NCI-H292 cells compared with azithromycin and clarithromycin.

OBJECTIVES: Mucus hypersecretion is a prominent feature in patients with chronic respiratory tract infections such as cystic fibrosis and diffuse panbronchiolitis, and the clinical effectiveness of macrolide antibiotics has been reported in these patients. Because human neutrophil peptide-1 (HNP-1), an antimicrobial peptide in neutrophils, exists in high concentrations in the airway fluid of these patients, we examined the direct effect of HNP-1 on MUC5AC mucin production using NCI-H292 cells. The effects of macrolide antibiotics on the response were also examined. METHODS: MUC5AC synthesis was assayed using RT-PCR and ELISA. Phosphorylation of ERK1/2 was determined by western blotting. RESULTS: Stimulation with HNP-1 or lipopolysaccharide (LPS) derived from Pseudomonas aeruginosa increases the production of MUC5AC mRNA and protein, and an additive effect was found upon co-stimulation with both HNP-1 and LPS. Azithromycin and clarithromycin had inhibitory effects on overproduction of MUC5AC induced by HNP-1 or LPS stimulation. Telithromycin also had an inhibitory effect on MUC5AC production induced by LPS, but not on production by HNP-1. Phosphorylation of ERK1/2 was induced by HNP-1 or LPS stimulation, and azithromycin, clarithromycin and telithromycin had inhibitory effects on ERK1/2 phosphorylation induced by LPS, but not by HNP-1. CONCLUSIONS: These findings suggest that neutrophil-derived defensins as bacterial components contribute to excessive mucus production in patients with respiratory tract infections, and that macrolide and ketolide antibiotics directly inhibit these actions by interfering with intracellular signal transduction. However, the mechanism of telithromycin inhibition of MUC5AC synthesis may differ from the response induced by azithromycin and clarithromycin.

[Case of nonspecific interstitial pneumonia associated with aortitis syndrome].

A 32-year-old woman was admitted to our hospital because of fever and back pain. Two months previously, she had been given a diagnosis of bacterial pneumonia based on the same symptoms and recovered after antibiotic treatment. Chest CT scans on admission showed a consolidation and thickened pleura in the right lower lobe. Bronchoalveolar lavage fluids showed an alveolar hemorrhage. Lung biopsy specimens showed thickened pulmonary arteries and fibrotic nonspecific interstitial pneumonia (NSIP). Three years later, she was admitted with fever and pain of the left arm and aortitis syndrome was diagnosed. In this case of NSIP pattern associated with aortitis syndrome we speculate that repeated pulmonary infarction and alveolar hemorrhages caused the NSIP pattern.

Pirfenidone inhibits the expression of HSP47 in TGF-beta1-stimulated human lung fibroblasts.

Pirfenidone (5-methyl-1-phenyl-2-(1H)-pyridone) is a novel anti-fibrotic and anti-inflammatory agent that inhibits the progression of fibrosis in animal models and patients with idiopathic pulmonary fibrosis (IPF). Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen and plays an important role in the pathogenesis of IPF. The present study evaluated the in vitro effects of pirfenidone on expression of HSP47 and collagen type I in cultured normal human lung fibroblasts (NHLF). Expression levels of HSP47 and collagen type I in NHLF stimulated by transforming growth factor (TGF)-beta1 were evaluated genetically, immunologically and immunocytochemically. Treatment with TGF-beta1 stimulated both mRNA and protein expressions of both HSP47 and collagen type I in NHLF, and pirfenidone significantly inhibited this TGF-beta1-enhanced expression in a dose-dependent manner. We concluded that the anti-fibrotic effect of pirfenidone may be mediated not only through direct inhibition of collagen type I expression but also at least partly through inhibition of HSP47 expression in lung fibroblasts, with a resultant reduction of collagen synthesis in lung fibrosis.

[A case of mycoplasmal pneumonia with bronchiolitis treated with steroids].

A 37-year-old woman admitted elsewhere for a high fever, dry cough, stridor, and dyspnea was found in chest radiography and computed tomography on admission to have a thickened bronchial wall with centrilobular nodules in both lower lobes and skipped consolidations in the lower and middle lobe of the right lung. She had been diagnosed with mycoplasmal pneumonia because of high Mycoplasma pneumoniae antibody titer, so clarithromycin (CAM) was administrated. She was referred to us due to hypoxia with obstructive impairment in the pulmonary function test. Ventilation/perfusion radioisotope in the lung scan indicated heterogeneous distribution without mismatch, suggesting bronchiolitis obliterans due to M. pneumoniae pneumonia, so steroids were started. Five weeks of steroid administration ameliorated clinical symptoms, hypoxia, and abnormal shadows, but obstructive impairment diod not disappear completely. Early administration of steroid with antibiotics is required for bronchiolitis obliterans caused by M. pneumoniae. We review cases of mycoplasmal bronchiolitis reported in Japan.

Sarcoidosis accompanied by systemic lupus erythematosus and autoimmune hepatitis.

A 52-year-old woman was admitted to our hospital for further examination of blurred vision, abnormal lung shadows and an elevated level of angiotensin-converting enzyme. Sarcoidosis was suspected, however, careful history taking revealed the existence of photosensitivity and polyarthralgia. Laboratory tests showed lymphocytopenia, liver dysfunction, hypergammaglobulinemia, and positive anti-nuclear, anti-double stranded DNA and anti-smooth muscle antibodies. Liver biopsy examination showed chronic active hepatitis. She was diagnosed with the triplex of sarcoidosis, systemic lupus erythematosus and autoimmune hepatitis. Marked improvement was noted after corticosteroid therapy.

[A case of sarcoidosis with diabetes insipidus].

A 15-year-old girl was admitted to our hospital because of polydipsia, polyuria, bilateral hilar lymphadenopathy and uveitis. A diagnosis of sarcoidosis with central diabetes insipidus was made by radiological, serological, bronchoalveolar lavage examinations, fluid restriction test and vasopression test. Prednisolone therapy improved all of her clinical findings except diabetes insipidus. So she had to continue intranasal 1-desamino-8-arginine vasopressin (DDAVP) therapy. In addition, we reviewed the clinical features of 27 patients of sarcoidosis with diabetes insipidus reported in Japan. They included 12 patients in young men and 21 patients having uveitis. These patients showed low frequency of lung complications in comparison with sarcoidosis without diabetes insipidus. Steroid therapy improved the symptoms of diabetes insipidus in only 3 patients, and all these 3 patients started steroid therapy within 1 month after the onset. Therefore we think that early diagnosis and treatment are important. Though central neurosarcoidosis was generally considered to have poor prognosis, there were only 3 patients who had recurrence by steroid tapering.

Elevated BALF concentrations of alpha- and beta-defensins in patients with pulmonary alveolar proteinosis.

Defensins are endogenous antibiotics and regulators of inflammation, immunity and wound repair. Their concentrations are substantially increased in bronchoalveolar lavage fluid (BALF) of patients with infectious lung diseases. alpha-defensin (HAD) levels are also elevated in patients with idiopathic pulmonary fibrosis (IPF) and correlated with the decline in pulmonary function tests, suggesting the association of defensins with the pathogenesis of interstitial lung diseases. The aim of this study was to determine the profile of defensins in interstitial lung diseases. Serum and BALF levels of HAD and beta-defensin 1 and 2 (HBD-1, and -2) were measured by radioimmunoassay in 63 patients with interstitial lung diseases, including idiopathic pulmonary alveolar proteinosis (PAP), IPF, nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP) and pulmonary sarcoidosis, and in 9 healthy volunteers as controls. Levels of HAD in BALF of patients with PAP were significantly higher than those in controls and patients with COP and sarcoidosis. Serum levels of HAD in all groups were significantly higher than those in controls. Levels of HBD-1 and -2 in BALF of patients with PAP were extremely high in all subjects. Serum levels of HBD-1 were higher in all patient groups, with the exception of those with PAP, and those of HBD-2 were also higher in patients with IPF and sarcoidosis, compared with controls. BALF of PAP patients, but not IPF patients and controls, expressed antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus. Our findings suggest different kinetics of HAD and HBD-1 and -2 in serum and BALF of interstitial lung diseases and that these antimicrobial peptides in the airway lumen may contribute to prevention of bacterial airway infections in PAP.

[A case of rheumatoid lung complicated by SELAPINA-induced pneumonia].

SELAPINA is generic product of PL granule which is one of the most common forms of combination remedies for the common cold in Japan, and includes acetaminophen. We report a case of SELAPINA-induced pneumonia successfully treated with glucocorticoid pulse therapy followed by orally administered prednisolone. A 68-year-old woman, who had been treated for rheumatoid arthiritis with pulmonary involvement, took SELAPINA with an antibiotic for 6 days because of her cold symptoms. She then suffered a high fever, cough, dyspnea, vomiting and diarrhea. Chest radiograph and high-resolution computed tomography (HRCT) scan revealed diffuse interstitial shadows. SELAPINA-induced pneumonia was diagnosed because the blastoid transformation test using her peripheral blood lymphocytes was positive on stimulation with SELAPINA, but negative for other medicines.

Elevated levels of interferon gamma-inducible protein-10 and epithelial neutrophil-activating peptide-78 in patients with pulmonary sarcoidosis.

OBJECTIVE AND BACKGROUND: Interferon gamma-inducible protein (IP)-10 and epithelial neutrophil-activating peptide (ENA)-78 belong to the CXC chemokine family and are important factors in inflammatory lung diseases. In sarcoidosis, the potential role of IP-10 to regulate the migration and activation of T-cells towards sites of sarcoid activity has been suggested. METHODS: In this study, the concentrations of IP-10 and ENA-78 in the serum and BAL fluid of patients with different stages of active pulmonary sarcoidosis (n=41) and healthy subjects (n=12) were measured by enzyme-linked immunosorbent assay to evaluate the contribution of these CXC chemokines to this disease. RESULTS: Serum and BAL fluid concentrations of IP-10 and BAL fluid levels of ENA-78 in patients with sarcoidosis were significantly higher than those in control subjects. The serum levels of IP-10 were significantly increased only in patients with stages I and II sarcoidosis, while BAL fluid levels of ENA-78 were increased only in stage III sarcoidosis. In addition, serum concentrations of IP-10 were elevated in patients with extrapulmonary lesions compared with those without such lesions. In patients with sarcoidosis, IP-10 concentrations in BAL fluid correlated with lymphocyte proportions in BAL fluid. CONCLUSION: IP-10 may play an important role in regulating lymphocytes into the lung and that ENA-78 may be associated with lung parenchymal disease in pulmonary sarcoidosis.

Interstitial pneumonia caused by inhalation of fumes of nickel and chrome.

Two male industrial painters were admitted to hospital with dry cough and dyspnoea on exertion following a tank coating operation using a high-temperature spray paint consisting of a nickel-chromium alloy. Both patients showed hypoxaemia, peripheral leukocytosis, high levels of serum cytokines and bilateral ground-glass opacities on a chest CT scan. They were diagnosed with interstitial pneumonia caused by inhalation of nickel and chrome fumes and successfully treated with corticosteroid. These are rare cases of interstitial pneumonia associated with nickel/chromium inhalation.

[Three cases of chronic bird fancier's lung associated with the use of feather bedclothes].

We report here 3 cases of chronic bird fancier's lung diagnosed immunologically using antibodies to pigeon dropping extract. None of the patients were bird fanciers but had indirect exposure to birds in their living environment, and had been using feather-filled duvets or pillows for a long time. Two of 3 cases were positive for environmental provocation tests and 2 cases had pathological findings of hypersensitivity pneumonitis such as multinucleated giant cells and non-necrotizing epithelioid cell granulomas. One case was resistant to steroid therapy alone and was successfully treated by coadministration of prednisolone and cyclosporin A. Another case was treated by steroid alone but died of acute exacerbation of unknown cause. These cases suggest that not only feathers but two or more kinds of bird-related antigens were involved in the sensitization immunology and development of bird fancier's disease, and that clinicians should perform thorough history taking with environmental surveillance relevant to birds.

[A case of multiple pulmonary arteriovenous fistulae associated with hereditary hemorrhagic telangiectasia that deteriorated during pregnancy].

A 29-year-old woman was admitted to our hospital because of persistent breathlessness on exertion after the delivery of her second child. Although at the age of 26 she had been given a diagnosis of multiple pulmonary arteriovenous fistula (PAVF), treatment was not done because of the absence of symptoms. An intrauterine growth retardation (IUGR) due to hypoxemia occurred during the second pregnancy, and then she delivered a 1,283g baby by cesarean section in the 36th gestation week. Her symptoms and hypoxemia improved after transcatheter embolization. Hereditary hemorrhagic telangiectasia was diagnosed on the basis of recurrent epistaxis since her childhood, pulmonary and hepatic vascular abnormality (PAVF and hepatic arterioportal shunt) and telangiectasis of the buccal mucosa and tongue. We should consider an early treatment of PAVF for young female because pregnancy may induce increase of arteriovenous shunt, fatal hemoptysis, infertility, miscarriage and IUGR.