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To the Editor: Influenza is a serious disease that can spread around the world in seasonal epidemics, resulting in the deaths of an estimated 250,000 to 500,000 people every year [1]. Vaccination is the most effective method for preventing secondary complications and the risk of influenza-related hospitalisation and death. The influenza vaccine is safe in general, and the most common side-effects, such as injection-site reaction, pain, fever, myalgia and headache, are not important clinically [2]. However, a few case reports of interstitial lung disease (ILD) caused by influenza vaccine have been published. We report a case of influenza vaccine-induced ILD with a review of the literature. A 75-yr-old female was referred to our hospital (Komatsu Municipal Hospital, Komatsu, Japan) for evaluation of fever and chest radiograph abnormalities in November 2011. 2 weeks previously she had received the influenza vaccine (trivalent inactivated vaccine: A/California/7/2009 [H1N1]-like, A/Victoria/210/2009 [H3N2]-like, and B/Brisbane/60/2008-like antigens). She had developed a fever 1 week before admission, and a chest radiograph revealed patchy airspace infiltrates in both lungs (fig. 1a). She received garenoxacin without any improvement and was then referred to our hospital for further evaluation. She had a medical history of hypertension, anaemia and chronic renal failure due to diabetes, and had started regular haemodialysis at the age of 74 yrs. She had no past history of pulmonary disease and her chest radiograph the previous month was normal. Her medications included valsartan, furosemide, isosorbide dinitrate and cilnidipine, which had remained unchanged for 2 yrs. She also had an insulin injection every day. She was a nonsmoker and had no allergies to foods …

Summary Background Autoantibodies against aminoacyl-tRNA synthetases (ARS) have been found to be highly specific for polymyositis and dermatomyositis (PM/DM) and to correlate strongly with complicating interstitial pneumonia (IP). The aim of the present study was to compare the clinical presentations of anti-ARS antibody-positive IP patients with or without manifestations of PM/DM. Methods We retrospectively examined 36 IP patients with anti-ARS antibodies. Sixteen patients presented with and 20 without the features of PM/DM. They were divided into PM/DM-IP and idiopathic-IP (IIP) groups. Clinical symptoms, findings on physical examination, laboratory data, pulmonary function, computed tomography (CT), and bronchoalveolar lavage fluid (BALF) cell counts were compared. Results Skin findings, myalgia, and elevation of serum creatinine kinase were found in the PM/DM-IP group. Features common to both groups included: volume loss in lower bilateral lobes; ground-glass opacities, reticular shadows and traction bronchiectasis on chest CT; high percentage of lymphocytes (IIP: 44.0% ± 21.0% (mean ± SD), PM/DM-IP: 50.5% ± 23.5%) and low CD4/8 ratios (IIP: 0.36 ± 0.34, PM/DM-IP: 0.44 ± 0.42) in BALF; decreased pulmonary function, including percentage of predicted vital capacity (VC) (IIP: 80.1% ± 15.4%, PM/DM-IP: 73.6% ± 16.4%), residual volume (RV) (IIP: 70.7% ± 21.7%, PM/DM-IP: 71.5% ± 17.1%), total lung capacity (TLC) (IIP: 73.4% ± 13.6%, PM/DM-IP: 71.6% ± 13.0%), and diffusing capacity DLco (IIP: 57.5% ± 26.7%, PM/DM-IP: 46.4% ± 10.3%). Both groups achieved good responses to initial corticosteroid or immunosuppressant therapy. Conclusion Patients with anti-ARS antibody-positive IP have common pulmonary manifestations regardless of the presence of PM/DM.

Chymase is a chymotrypsin-like serine protease that is present in mast cells. Its activities include various effects associated with inflammatory responses. But little is known about the effects of chymase in pulmonary fibrosis. The mouse silicosis model was induced by intratracheal injection of 10 mg silica. The Ashcroft pathological score and the hydroxyproline content of lungs were measured to evaluate the effect of a chymase inhibitor, 2-[4-(5-fluoro-3-methylbenzo[b]thiophen-2-yl)sulfonamido-3-methanesulfonylphenyl] thiazole-4-carboxylic acid (TY-51469). The cellular composition and cytokine levels in bronchoalveolar lavage fluid (BALF) were also examined. Following TY-51469 treatment, the lung fibrosis score and hydroxyproline level were significantly reduced, and the number of neutrophils and the levels of macrophage inflammatory protein-2, monocyte chemoattractant protein-1, and transforming growth factor-β₁ in BALF were reduced on day 21. The administration of TY-51469 at an early stage showed a greater reduction of fibrosis compared to administration at a later stage. The neutrophil number in BALF in mice treated with TY-51469 both at an early stage and late stage was significantly reduced. The level of mouse mast cell proteinase-4 mRNA increased with time in silica-induced fibrosing lung tissue. These results show that the chymase inhibitor TY51469 suppresses the migration of neutrophils, which results in the suppression of lung fibrosis.

金沢大学医薬保健研究域医学系, Background and Objective: The purpose of this study was to evaluate the relationship between the wall structure assessed by using endobronchial ultrasonography (EBUS) and bronchial hyperresponsiveness in patients with asthma. Methods: Twenty-four patients with stable asthma and 11 individuals without asthma were studied. EBUS was performed with a radial 20-MHz ultrasonic probe inserted into the intermediate bronchus undergoing flexible bronchoscopy to assess the airway wall structure. The percentage of airway wall thickness {WT%; defined as [(ideal outer diameter-ideal luminal diameter)/ideal outer diameter] × 100} was determined by EBUS. We measured bronchial hyperresponsiveness to methacholine [the provocative concentration of methacholine causing a decrease of 20% or more in forced expiratory volume in 1 s (PC20)]. Results: Percentage wall thickness measured by EBUS was significantly greater in patients with asthma than that in subjects without asthma (P < 0.01). The evaluation of the laminar structure using EBUS indicated that the thickness of the second layer in patients with asthma was greater than that in subjects without asthma (P < 0.05). PC20 was negatively correlated with the thickness of the second layer (r=0.52, P < 0.01) but was not significantly correlated with other layers in patients with asthma. Conclusions: The evaluation of the bronchial mural structure using EBUS might be advantageous for assessing the relationship between airway wall remodeling and bronchial hyperresponsiveness. © 2010 Lippincott Williams & Wilkins.

金沢大学医薬保健研究域医学系, Background: The clinical features of pneumocystis pneumonia (PCP) differ according to the predisposing factors responsible for immunosuppression. Although PCP in patients with acquired immunodeficiency syndrome (AIDS) has been extensively described, its characteristics in non-AIDS patients, such as those with malignancies, are not thoroughly documented. Study objective: To characterize and compare the clinical and imaging features of PCP in patients with malignancies with those in AIDS patients. Design: A multi-center retrospective study. Patients and Measurements: We evaluated the clinical and radiological features of PCP in 21 patients with malignancies and in 17 with AIDS. Clinical presentation, serum markers, oxygenation, CT findings, and outcome were examined. Results: The patients with malignancies showed shorter durations of symptoms before PCP was diagnosed. The levels of serum markers and the oxygenation index did not differ. CT showed diffuse or widespread ground-glass opacity (GGO) in all of the patients evaluated. None of the AIDS patients demonstrated consolidation, whereas half of the patients with malignancy showed consolidation along with GGO. The extent of GGO scored on CT images was significantly greater in the AIDS patients. No correlation was observed between the CT findings and other clinical parameters. All of the AIDS patients recovered from PCP, whereas six patients with malignancies died within a month after the onset of PCP. Conclusion: The characteristics of the CT images differed between the patient groups with different underlying disorders, although it remains to be determined whether CT findings are associated with other clinical features or are predictive of the outcome of PCP. © 2010 The Japanese Society of Internal Medicine.

A 19-year-old woman with acute myeloid leukemia (M1) was treated with allogeneic hematopoietic stem cell transplantation. She was diagnosed with skin graft-versus-host disease 27 days after the transplantation. She was admitted to the Dept. of Respiratory Medicine at Kanazawa University Hospital, because she complained of progressive obstructive ventilatory impairment. A high-resolution computed tomography (CT) scan showed centrilobular small nodules. A chest CT scan (inspiratory phase and expiratory phase) revealed hyperlucent areas forming a mosaic pattern. A ventilation-perfusion scan showed matched unequal distribution. The pathological diagnosis made using biopsied lung, obtained by a right lower partial lobectomy, was constrictive bronchiolitis. Pulmonary function tests on admission showed mixed ventilatory impairment. %Residual volume(RV)/total lung capacity(TLC) was measured by the closed-circuit helium dilution method and was within the upper limit of the normal range. However, %RV/TLC measured by a body plethysmograph indicated a value of 258.1%. We believe that the difference in the %RV/TLC values reflected air trapping caused by bronchiolitis obliterans. Thus, the lung volume fraction measured by body plethysmograph was useful for diagnosing bronchiolitis obliterans in this case. [Rinsho Byori 58 : 906'-911, 2010].

Gefitinib is an orally active epidermal growth factor receptor tyrosine kinase inhibitor, and it shows favorable antitumor activity against chemorefractory nonsmall cell lung cancer (NSCLC). However, patients with NSCLC have few treatment options available if they are refractory to gefitinib. We describe a 49-year-old patient with NSCLC who had a complete response to initial gefitinib that lasted for 12 months. The tumor relapsed, and the patient received cytotoxic chemotherapy. However, despite chemotherapy, the patient had radiographic progression of lung metastases and we commenced retreatment with gefitinib, showing a remarkable effect. Epidermal growth factor receptor (EGFR) gene analysis showed deletion mutations in codon 745-750 in exon 19 and EGFR gene amplification. Our case shows that after retreatment with gefitinib, patients may show a remarkable response if they showed a remarkable response to initial gefitinib administration and if a certain time has elapsed since the previous gefitinib treatment.

We report a case of pulmonary proteinosis detected at an early stage and followed up on chest CT. A 49-year-old man underwent detailed examinations because of abnormal shadows on chest CT taken on a routine medical examination. The chest CT revealed almost symmetrical ground glass opacities (GGOs) in both lungs with thickened alveolar septa. We could not make a definitive diagnosis even with bronchoalveolar lavage and transbronchial lung biopsy, but after about half a year, the GGOs increased. VATS-biopsy demonstrated alveoli filled with PAS-positive granular materials, and we made a diagnosis of pulmonary alveolar proteinosis. This case was found at an early stage and we were then able to follow up the disease.

Background The role of angiotensin II type 2 receptor (AT2) in pulmonary fibrosis is unknown. To evaluate the influence of angiotensin II type 1 receptor (AT1) and AT2 antagonists in a mouse model of bleomycin (BLM)-induced pulmonary fibrosis. Methods We examined effects of the AT1 antagonist (AT1A) olmesartan medoxomil (olmesartan) and the AT2 antagonist (AT2A) PD-123319 on BLM-induced pulmonary fibrosis, which was evaluated by Ashcroft's pathological scoring and hydroxyproline content of lungs. We also analyzed the cellular composition and cytokine levels in bronchoalveolar lavage fluid (BALF). Results With olmesartan, the lung fibrosis score and hydroxyproline level were significantly reduced, and lymphocyte and neutrophil counts and tumor necrosis factor (TNF)-α levels in BALF were reduced on day 7. On day 14, macrophage and lymphocyte counts in BALF were reduced, accompanied by a reduction in the level of transforming growth factor (TGF)-β1. With PD-123319, the lung fibrosis score and hydroxyproline level were reduced. On day 7, macrophage, lymphocyte, and neutrophil counts in BALF were reduced, accompanied by reductions in TNF-α and monocyte chemoattractant protein (MCP)-1 levels. On day 14, macrophage, lymphocyte, and neutrophil counts in BALF were also reduced, accompanied by a reduction in the level of macrophage inflammatory protein (MIP)-2 level but not TGF-β1. Conclusion Both AT1 and AT2 are involved in promoting interstitial pneumonia and pulmonary fibrosis via different mechanisms of action.