Determinants of Long-Term Persistence with Tiotropium Bromide for Chronic Obstructive Pulmonary Disease.

Tiotropium bromide, a long-acting anticholinergic agent, improves pulmonary function and quality of life of patients suffering from chronic obstructive pulmonary disease (COPD). We retrospectively examined the factors that determine the long-term persistence with tiotropium bromide. Among 6,301 patients who underwent pulmonary function tests in our pulmonary clinic between 2006 and 2009, 644 met the following criteria: 1) age > 40 years, 2) ≥ 20 pack-years smoking history, and 3) forced expiratory volume in 1 sec / forced vital capacity ratio < 0.7. The clinical information, including the prescription of tiotropium, was obtained from the patients' records. Tiotropium was administered to 255 patients (40%), of whom 48 (19%) discontinued treatment within 1 year, and 65 (25%) discontinued treatment within the median observation period of 32 months. The drug was discontinued because of ineffectiveness in 35 patients (73%), and because of adverse drug effects in 13 patients (27%). Young age, current smoking, absence of respiratory symptoms alleviation, and less severe disease characterized by a) mild airflow limitation, b) mild to moderate emphysema, or c) no exacerbation of COPD during the 1(st) year of treatment were predictors of drug discontinuation.

Predictors of osteoporosis and vertebral fractures in patients presenting with moderate-to-severe chronic obstructive lung disease.

Bone mineral density (BMD) alone does not reliably predict osteoporotic fractures. The Fracture Risk Assessment Tool (FRAX) was developed to estimate the risk of fracture in the general population. This study was designed to identify predictors of osteoporosis and vertebral fractures in patients presenting with chronic obstructive pulmonary disease (COPD). We studied 85 patients (mean age = 75 years; 92% men) with moderate to very severe COPD. Osteoporosis and vertebral fractures were diagnosed with dual energy X-ray absorptiometric scan and vertebral X-rays, respectively. Patient characteristics, including age, gender, body mass index (BMI), and results of pulmonary function tests, chest computed tomography scan, blood and urinary biomarkers of bone turnover were recorded, and a FRAX score was calculated by a computer-based algorithm. Osteoporosis, defined as a T score < -2.5, found in 20 patients (24%), was associated with female gender, BMI, dyspnea scale, long-term oxygen therapy (LTOT), vital capacity (VC), emphysema score on computed tomography, measurements of serum and urinary biomarkers of bone turnover. Vertebral fractures, diagnosed in 29 patients (35%), were strongly correlated with age, LTOT, VC, and forced expiratory volume in 1 sec, treatment with oral corticosteroid or warfarin, and weakly associated with the presence of osteoporosis. There was no correlation between FRAX score and prevalence of vertebral fractures, suggesting that neither BMD alone nor FRAX score would predict the presence of vertebral fractures in COPD patients. A disease-specific algorithm to predict osteoporotic fractures is needed to improve the management of patients suffering from COPD.

Strain-specific phenotypes of airway inflammation and bronchial hyperresponsiveness induced by epicutaneous allergen sensitization in BALB/c and C57BL/6 mice.

BACKGROUND: Allergen sensitization through a disrupted skin barrier appears to play a prominent role in the development of atopic diseases, including allergic asthma. The role of the genetic background in immunological and physiological phenotypes induced by epicutaneous sensitization is undetermined. METHODS: BALB/c and C57BL/6 mice were sensitized either epicutaneously by patch application of ovalbumin (OVA) or systemically by intraperitoneal injection of OVA with alum before exposure to aerosolized OVA. The concentrations of OVA-specific immunoglobulin in serum and cytokines in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay. The severity of airway inflammation was evaluated by cell counts in BALF, and bronchial responsiveness to methacholine was measured by the flexiVent system. RESULTS: The production of OVA-specific IgG1 and IgE was greater in the epicutaneously sensitized BALB/c than C57BL/6 mice. In contrast, both eosinophilic airway inflammation and bronchial responsiveness to methacholine were more prominent in the C57BL/6 than in the BALB/c mice. The concentrations of interleukin-4 increased significantly in the BALF from C57BL/6 mice only. No between-strain differences were observed after intraperitoneal sensitization. CONCLUSIONS: The C57BL/6 mouse is a more appropriate model than the BALB/c mouse to study the relationship between skin barrier dysfunction and the pathogenesis of allergic asthma.

Spontaneous regression of primary endobronchial extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) of pulmonary origin is a relatively rare disease. In particular, reports of MALT lymphoma occurring and localized in the trachea or bronchus have been limited. Pulmonary MALT lymphoma has been reported to demonstrate spontaneous regression, whereas there is only one reported case of spontaneous regression of primary endobronchial MALT lymphoma. We herein report the case of a 70-year-old man with primary endobronchial MALT lymphoma who showed spontaneous regression with an interest of endobronchial findings.

Pleomorphic carcinoma showing rapid growth, multiple metastases, and intestinal perforation.

Pleomorphic carcinoma is a rare and very aggressive subtype of lung cancer that tends to grow rapidly and invade adjacent structures. Here we report a case of pleomorphic carcinoma with rapid growth, multiple metastases, and intestinal perforation. A 46-year-old man was admitted to our hospital because of lung abscess. Several antibiotics were administered for 2 weeks, but his condition did not improve. F18-fluorodeoxyglucose positron emission tomography revealed high uptake in the right lung, stomach, and pancreas. CT-fluoroscopic lung biopsy was performed, and a diagnosis of pleomorphic carcinoma was made. His performance status worsened each day, and the lung tumor grew within 1 month. In addition, sudden severe abdominal pain and tenderness developed 10 days after lung biopsy. He was diagnosed with gastrointestinal perforation, and he underwent surgery. However, he died 2 weeks after the surgery. Autopsy revealed the presence of an enormous tumor in the right lung and multiple metastases in the stomach, duodenum, intestine, bilateral kidneys, pancreas, gallbladder, right adrenal gland and thyroid.

Eosinophilic lung disease complicated by Kimura's disease: a case report and literature review.

Kimura's disease (KD) or eosinophilic lymphogranuloma is a rare chronic inflammatory disorder of unknown etiology that occurs primarily in Asians. A 51-year-old man diagnosed three years earlier with KD of a left neck nodule was admitted to our hospital with a productive cough and pulmonary infiltration. Bronchoscopy was performed, and a diagnosis of eosinophilic lung disease (ELD) was made. The patient's condition improved after receiving corticosteroid treatment. Complications such as nephrotic syndrome have been reported in patients with KD; however, ELD has not been previously described. To the best of our knowledge, this is the first report of ELD related to KD.

Tuberous sclerosis diagnosed by incidental computed tomography findings of multifocal micronodular pneumocyte hyperplasia: a case report.

INTRODUCTION: The majority of multifocal micronodular pneumocyte hyperplasia associated with tuberous sclerosis complex is diagnosed with the classical clinical triad of seizures, mental retardation, and skin lesions. We report a rare case of tuberous sclerosis complex with no classical clinical findings, which was diagnosed through incidental computed tomography findings of multiple nodular lesions of multifocal micronodular pneumocyte hyperplasia. CASE PRESENTATION: A chest computed tomography scan of a 51-year-old Japanese woman showed multiple nodular ground-glass opacities that were not seen on chest X-ray. Video-assisted thoracoscopic surgery was performed. A histological examination demonstrated type II pneumocyte hyperplasia with thickened fibrotic alveolar septa, which was consistent with multifocal micronodular pneumocyte hyperplasia. Brain magnetic resonance imaging displayed multiple cortical tubers, and abdominal computed tomography showed bilateral renal angiomyolipoma. Our patient was finally diagnosed as having tuberous sclerosis complex with multifocal micronodular pneumocyte hyperplasia, although she had no episodes of epilepsy, no skin lesions, and no family history. CONCLUSIONS: Multifocal micronodular pneumocyte hyperplasia with latent tuberous sclerosis complex should be considered in the differential diagnosis of multiple ground-glass opacities.