[A case of follicular bronchiolitis in which progressive bronchiectasis developed over 7 years].

A 53-year-old man presented to our hospital with cough in August 2004. Chest computed tomography showed an anterior mediastinal tumor, centrilobular nodules and mild bronchiectasis. Centrilobular nodules were improved by the administration of clarithromycin, and we resected an anterior mediastinal tumor (thymoma). Partial lung resection was also performed, and a diagnosis of follicular bronchiolitis was established. The number of centrilobular nodules increased after cessation of the clarithromycin, and its administration was reinitiated; however, the patient's bronchiectasis and airway obstruction worsened. Steroid administration was begun in January 2010; thereafter, pulmonary function, bronchial wall thickness, cough and shortness of breath improved. Since April 2004, the patient has experienced 12 episodes of airway infection. Careful attention should be paid to recurrent airway infection, progressive bronchiectasis and airway obstruction in patients with follicular bronchiectasis.

[Comparison between pandemic H1N1 2009 influenza pneumonia and seasonal influenza pneumonia in adults].

We compared 126 cases of seasonal influenza pneumonia (seasonal flu) reported between January, 1996 and March, 2009, with 10 cases of laboratory-confirmed pandemic influenza (H1N1) 2009 influenza virus pneumonia (novel flu), based on clinical condition, computed tomography (CT) findings, severity, treatment, and prognosis, to clarify the characteristics of this novel flu. The mean age of subjects was 52.4 years in the novel flu group and 64 years in the seasonal flu group, and novel flu patients were younger than seasonal flu patients. Seasonal flu patients had more underlying diseases than did novel flu patients. The median duration from illness onset to hospitalization was 4 days in both groups. Primary viral pneumonia was present in 70% of novel flu cases and 31% of seasonal flu cases. The proportion of primary virus pneumonia was higher in novel flu patients, and the disease severity of the seasonal flu group was more severe than that of the novel flu group. White blood cell and lymphocyte counts were lower in novel flu patients, and chest CT images showed bilateral shadows and pure ground-glass opacities more frequently in the novel flu cases. There were no differences in treatment, number of days required for the fever to subside, or mortality between the groups.

[Eight cases of idiopathic pulmonary alveolar proteinosis followed up for more than 4 years].

BACKGROUND: Few reports exist regarding the long-term clinical course of idiopathic pulmonary alveolar proteinosis. PURPOSE AND METHODS: We retrospectively studied the clinical courses of 8 patients. The patients were 4 men and 4 women aged 48.4 +/- 14.0 years (mean +/- SD) with idiopathic pulmonary alveolar proteinosis followed up for a minimum of more than 4 years. Mean follow-up was 13 years and 6 months (4-22 years and 9 months). RESULTS: There were 15 instances of whole-lung lavage and/or bronchoalveolar lavage in 7 patients, and lavage was effective 40% of cases. Spontaneous improvement occurred 16 times and exacerbation occurred 7 times in 8 patients. On chest X-ray films, the shadows disappeared in 5 of 8 (62.5%) patients, and in 4 of 5 patients, shadows disappeared 5 or more years after diagnosis of pulmonary alveolar proteinosis. Pulmonary shadows have not disappeared in the remaining 3 patients at the time of writing but have shown improvement compared with first presentation. There were no deaths. CONCLUSION: As indicated in previous reports, the long-term outcome of idiopathic pulmonary alveolar proteinosis appears to be good.

[Clinical study of pneumocystis pneumonia in patients with rheumatoid arthritis].

We reviewed case of pneumocystis pneumonia (PCP) with rheumatoid arthritis. We administered the antirheumatic drug methotrexate (MTX) at the time of to 13 patients, corticosteroids to 11 patients and a tumor necrosis factor (TNF) inhibitor to 3 patients. Treatment for PCP was started on admission in all cases. We administered adrenocorticosteroids to all 13 patients with a PaO2 level < 70 Torr. Three patients were under respiratory management, and 4 patients died. By univariate analysis, prognostic indicators of death were: presence of acute respiratory distress syndrome (ARDS), peripheral blood neutrophil/lymphocyte ratio, serum albumin value, serum beta-D-glucan value, and AaDO2 and PaO2/FiO2 ratios. Readministration of a TNF inhibitor in 2 patients and MTX in 3 patients was possible after PCP remission. Even though we began treatment for PCP on the day of admission, 25% of patients died. PCP may occur in patients who are given MTX or a TNF inhibitor or both, and the clinician should endeavor to detect its onset as early as possible. Elucidation of the prognostic indicators of recovery may require multivariate analysis of many cases.

[A single-center prospective study of viral infection in community-acquired pneumonia in adults].

From July, 2008 to March, 2009, 125 adults with community-acquired pneumonia (CAP) who were admitted to our hospital were retrospectively investigated to elucidate the characteristics of viral infection in adult CAP in Japan. Nasopharyngeal swabs for real-time polymerase chain reaction for 7 types of influenza virus, rhinovirus, respiratory synctial virus, human metapneumovirus, parainfluenza virus, coronavirus, and enterovirus were obtained. Diagnoses of viral infections were established according to positive results in real-time polymerase chain reaction and influenza rapid diagnostic testing, and based on a fourfold increase in antibody titer of influenza virus antibody in paired sera. Overall, a pathogen was identified in 74 patients (59.8%). Of these pathogens, 47 (37.6%) were bacterial, 17 (13.6%) were viral, and 10 (8.0%) were mixed virus and bacterial infection. Influenza virus (n = 12; 9.6%), rhinovirus (n = 8; 6.4%), respiratory syncytial virus (n = 8; 6.4%), and parainfluenza virus (n = 6; 4.8%) were detected. Adenovirus, coronavirus or enterovirus was not detected. Sore throat was more frequently found in patients with viral pneumonia than in those with non-viral pneumonia. Higher age and pneumococcal pneumonia were factors which contributed to severity in the present cases. It is difficult to distinguish viral pneumonia from non-viral pneumonia by clinical findings, and there were few clinically meaningful differences in presentation and severity, and no differences in severity or outcomes according to either the presence or absence of viral infection. Further studies are needed to clarify the possible significance of viral infection in CAP.

[A case of pulmonary alveolar proteinosis which initially deteriorated rapidly with exacerbation of pulmonary nocardiosis, responded promptly to treatment of the pulmonary nocardiosis].

A 37-year-old man was admitted with complaints of continuous cough and sputum production for 1 month. Computed tomography (CT) of the chest revealed a solitary mass with a cavity in the apex of the left lung and bilateral ground-glass opacities (GGO). Thereafter, the patient complained of fever, and an increase in the mass shadow size and expansion of the ground-glass opacities were observed on serial CT. The patient was given diagnoses of pulmonary nocardiosis and pulmonary alveolar proteinosis by bronchoscopic examination. Serum anti-GM-CSF antibody tests were positive. On the basis of these findings, we diagnosed autoimmune pulmonary alveolar proteinosis. After beginning antituberculosis drugs and antibiotics, the tumor shadow and GGO reduced. The pulmonary alveolar proteinosis rapidly worsened on exacerbation of the pulmonary nocardiosis, but prompt overall improvement was obtained after treating the latter. We believe this to be a valuable case for examining the time progression of autoimmune pulmonary alveolar protein syndrome, because of the clinical course of the exacerbation, and the improvement in the pulmonary alveolar proteinosis after treatment of pulmonary nocardiosis.

[Hypersensitivity pneumonitis induced by Hypsizigus marumoreus].

We present the case of a 53-year-old woman who was employed at a mushroom (Pleurotus eryngii and Hypsizigus marumoreus) cultivation factory for 15 years. She was admitted to our hospital because of fever and dry cough. Chest radiography and CT scanning revealed diffuse ground glass opacity and centrilobular nodules in both lung fields. Serum KL-6 was elevated. In the bronchoalveolar lavage fluid, the CD4/CD8 ratio was reduced, and the lymphocyte fraction was very high. Transbronchial lung biopsy specimens showed lymphocyte alveolitis. After admission, the patient's symptoms improved rapidly without medication. Although these findings are compatible with hypersensitivity pneumonitis, it was difficult to identify a causative antigen. Serum antibody against Trichosporon was positive. A lymphocyte stimulation test of the peripheral blood was positive against extracts of P. eryngii and H. marumoreus. Furthermore, precipitins against the extracts of H. marumoreus were detected by a double immunodiffusion test. Therefore, we decided to conduct a challenge test using H. marumoreus. As an inhalation provocation test with H. marumoreus conducted in a sickroom caused the same clinical symptoms and signs as experienced in the workplace, we diagnosed hypersensitivity pneumonitis caused by H. marumoreus. A provocation test, in which antigen exposure is limited using a closed space, such as a sickroom, was simple, safe and effective for determining the antigen causing hypersensitivity pneumonitis.

[A case of Ehlers-Danlos syndrome suspected from pulmonary hematoma due to disruption of the lung].

A 20-year-old man was referred to our hospital due to hemoptysis. Chest CT showed a ground-glass opacity, suggesting pulmonary bleeding; however, a diagnosis was not obtained. At a follow-up examination after 2 months, Chest CT showed improvement of the ground-glass opacity, however a cavitary nodule had newly appeared. Four months later, another new nodule was found on chest X-ray film. Video-assisted thoracoscopic lung biopsy was performed for pathological diagnosis; disruption of the pleural, lung and blood vessels, and pulmonary hematoma were found. We thought of the fragility of the pleuro-pulmonary connective tissue and also thought of the probability of Ehlers-Danlos syndrome (EDS). A biochemical analysis of cultured dermal fibroblasts and molecular biological examination revealed decreased production of type III collagen in fibroblasts and COL3A1 mutation. We diagnosed this case as vascular EDS. EDS is one of the differential diagnoses in patients presenting hemoptysis and pulmonary hematoma due to disruption of the lung.

[Mucoid impaction of the bronchi caused by Schizophyllum commune which developed after discontinuation of itraconazole administration].

We report the case of a 75-year-old woman with mucoid impaction of the bronchi (MIB) due to Schizophyllum commune who improved with itraconazole (ITCZ) administration and relapsed after discontinuation of the drug. She improved again after readministration of ITCZ, and MIB has not recurred. This patient was not suffering from asthma and has been well without steroid administration. Reports of respiratory disorders due to S. commune have been increasing, and cases of allergic bronchopulmonary mycosis (ABPM), fungus ball, lung abscess, and pneumonia have been reported. Including this report, 12 cases of ABPM and MIB due to S. commune have been reported by Japanese authors. Treatment in these 12 cases included anti-fungal agent in 6, single steroid therapy in 3, combination therapy in 2, and bronchial toilet in 1 case. S. commune is not well recognized; however, one should suspect this fungus to be the causative pathogen when Aspergillus species are not detected or anti-Aspergillus antibody is negative.

Ehlers-Danlos syndrome with recurrent spontaneous pneumothoraces and cavitary lesion on chest X-ray as the initial complications.

A 17-year-old-man developed left-sided pneumothorax in 1995. Chest computed tomography (CT) showed a thick-walled cavity in the left lower lobe. Video-assisted thoracic surgery was performed, and pathologic findings of the resected lung showed a cavity, organizing hematoma, and a fibrous nodule. Fragility of connective tissue was suspected, and biochemical and molecular analysis showed reduction of type III collagen production and point mutation of the COL3A1 gene. The patient was diagnosed as having vascular-type Ehlers-Danlos syndrome (EDS). From 2002, the patient developed hemoptysis and bloody sputum once a year. Chest CT detected several nodules and cavities, which were regarded as hematomas with or without excretion. Several vascular changes including aneurysmal formations have been found since 2002, and an aneurysm of the left ulnar artery was resected. The patient continues to be followed regularly on an outpatient basis. We report a rare case of vascular-type EDS who developed pulmonary symptoms as an initial complication.

[Primary ciliary dyskinesia. A case report and comparison with 4 previous cases].

We encountered a 59-year-old man, whose chief complaints were sputum and dyspnea on effort. He had suffered from sinusitis since childhood, and chest computed tomography showed bronchiectasis. Electron microscopic examination of bronchial mucosa biopsied by bronchoscopy showed defect of the inner dynein arm in most of his cilia. We diagnosed primary ciliary dyskinesia. Seminal analysis showed no abnormalities, and the etiology of infertility remains unclear. The present case is the fifth case treated at our hospital. In this paper, we compared this case with 4 cases (2 cases of Kartagener's syndrome and 2 cases of primary ciliary dyskinesia without situs invertus) of our hospital, and findings of previous reports. Primary ciliary dyskinesia should be included in the differential diagnosis even in cases of mild bronchiectasis or normal mobility of sperm. Primary ciliary dyskinesia has more variety in radiological and clinical findings than has been recognized.

Changes in lung function and health status in patients with COPD treated with tiotropium or salmeterol plus fluticasone.

BACKGROUND AND OBJECTIVE: The effects of tiotropium, a long-acting anticholinergic drug, were compared with those of the combination of salmeterol, a long-acting beta(2)-agonist, and fluticasone, an inhaled corticosteroid, in patients with COPD. METHODS: A 4-month, randomized, open cross-over study of tiotropium, 18 microg once daily, versus salmeterol, 50 microg, plus fluticasone, 200 microg, twice daily, was conducted in patients with COPD. Efficacy was assessed by spirometry and responses to the St George's Respiratory Questionnaire (SGRQ). After 4 months, patients were asked to select their subsequent therapy and indicate the reasons for their selection. RESULTS: A total of 78 patients completed the study. There were no significant differences in the improvements in FEV(1) or SGRQ scores between the therapies. Similar numbers of patients selected tiotropium (42.3%) and salmeterol plus fluticasone (57.7%). However, those who preferred one of the therapies demonstrated greater improvements in SGRQ scores with that therapy. One subgroup of patients (30.8%) showed greater improvements in dyspnoea and FEV(1) in response to tiotropium, and the other subgroup of patients (35.9%) showed greater improvements in dyspnoea and FEV(1) in response to salmeterol plus fluticasone. Some patients (14.1%) selected salmeterol plus fluticasone because of positive effects on sputum expectoration. CONCLUSIONS: The study was unblinded and the results need to be interpreted with caution. However, tiotropium and salmeterol plus fluticasone had similar overall effects on pulmonary function and SGRQ scores in patients with COPD. Responses to the two therapies were heterogeneous, and the patients who showed greater improvements in FEV(1) or SGRQ scores with one of the therapies preferred it for their subsequent treatment.

[Long-term CT findings of X-linked agammaglobulinemia with bronchiectasis diagnosed in an adult].

We report a case of X-linked agammaglobulinemia who presented with bronchiectasis. The patient had suffered pneumonia about every five years since childhood until he presented to our hospital at age 34 years old. CT showed bronchiectasis predominantly in the right middle lobe, lingula, and lower lobes. Administration of antibiotics resulted in symptomatic relief. Episodes of recurrent pulmonary infection and bronchiectasis indicated congenital immunodeficiency disorder. Investigation of lymphocyte subsets and serum immunoglobulin values showed remarkable reduction of B cells, IgG 772 mg/dl, IgA 216 mg/dl, and IgM 29 mg/dl. Flow cytometric assessment combined with genetic analysis was performed, and the results showed decreased expression of monocyte Bruton's tyrosine kinase (BTK) and missense mutation of Btk gene. We diagnosed X-linked agammaglobulinemia. IgG remained above 600 mg/dl in this case, we have not administered immunoglobulin after discharge. He suffered from pneumonia in 2004 and 2006 and bronchiectasis has progressed. In this report, we present a case including CT findings over a period of 8 years.

[Autopsy case of diffuse pleural thickening presenting respiratory impairment and benign asbestos pleurisy].

A 51-year-old man presented with back pain in 1997. He had a 30-year-history of occupational asbestos exposure. His chest CT showed bilateral pleural thickening and pleural effusion. The pleural effusion of the right thorax exhibited both elevated level of adenosine deaminase and increased numbers of lymphocytes. Antituberculous chemotherapy had no effect on the exudates. Progressive bilateral pleural thickening were found on chest CT, and pulmonary function tests showed severe restrictive ventilatory impairments since 1998. Thoracoscopic pleural biopsy was conducted in 2001 to exclude pleural malignant mesothelioma. No malignancy was found in pleural samples. After 3-year observation and excluding other causes, he was given a diagnosis of benign asbestos pleurisy. In 2005, fibrotic changes were found in both lower lung fields in chest CT. He suffered from respiratory failure with carbon dioxide retention, and died in 2006. The autopsy disclosed asbestos-related lung diseases. We suspected that diffuse pleural thickening could be a major cause of fatal respiratory impairment in this case.

[A case of the metastatic calcification of trachea, bronchus, and lung].

A 43-year-old man with chronic renal failure who had been treated by continuous ambulatory peritoneal dialysis (CAPD) was admitted to our hospital because of dry cough. Blood gas analysis showed hypoxemia and metabolic alkalosis. Laboratory data showed elevated levels of phosphorus, BNP, and KL-6. Lung function tests showed restrictive ventilatory failure and impairment of diffusing capacity. Chest CT revealed centrilobular ground-glass opacification in both lung fields, irregular reticular abnormality in left lung field, and calcification around the left shoulder joint. Bronchoscopy revealed a white protruding lesion in the trachea and bronchial membranous portion. Calcified metastasis in the bronchus and lung was confirmed by transbronchial and lung biopsy. Because of no improvement by administration of sevelamer, he started with hemodialysis once a week in addition to CAPD. Cough and bilateral ground-glass opacity were improved.

[A case of human T lymphotropic virus type I-related lung disease in which Legionella pneumonia led to the diagnosis].

A 46-year-old man whose parents were from Nagasaki had a 24-hour bath system in his house. He had had a cough for 26 years and dyspnea for 2 years. He consulted our hospital because of the increase of his cough and dyspnea. Chest X ray and CT showed abnormal shadows in both lung fields and Legionella pneumophila type 3 was detected by sputum cultivation. The condition which appeared this time responded to antibiotic medication. However, the abnormal shadows in both lung fields and the abnormalities in respiratory function remained. The remaining abnormal shadows in both lung fields were considered to be the cause of his dyspnea for 2 years and cough for 26 years. Atypical lymphocytes with a floriform nucleus were observed in peripheral blood. Gene analysis detected monoclonal human T lymphotropic virus type I (HTLV-I) provirus DNA. We diagnosed as smoldering type adult-T-cell-leukemia (ATL). Thoracoscopic lung biopsy revealed fibrotic thickening of the interstitial tissue accompanied by structural destruction. The pathological changes in both lung fields were diagnosed as HTLV-I related lung disease and infiltration of ATL. Known pathogens of lung infection accompanying ATL include viruses, acid fast organisms, and fungi. Legionella pneumonia happened to be the opportunity leading to the diagnosis of HTLV-I related lung disease is this case.

Multiple tracheobronchial mucosal lesions in two cases of Churg-Strauss syndrome.

Churg-Strauss syndrome (CSS) is characterized by hypereosinophilia and a systemic necrotizing vasculitis seen almost exclusively in patients with asthma. The most common pathological findings in the chest in CSS are eosinophilic pneumonia, necrotizing vasculitis and granulomatous inflammation (extravascular granuloma). However, tracheobronchial mucosal lesions have rarely been reported in CSS. The authors report two patients with CSS who had multiple tracheobronchial mucosal lesions that were found by fibreoptic bronchoscopy. They were tiny nodular lesions and necrotizing bronchial inflammation with many eosinophils was observed upon pathological examination. The authors concluded that tracheobronchial mucosal lesions may be one of the manifestations of vasculitis seen in CSS.

Serum IgG and IgA antibodies to Chlamydia pneumoniae and severity of emphysema.

OBJECTIVE: Chronic Chlamydia pneumoniae infection has been identified serologically in patients with COPD. The aim of this study was to examine whether the severity of emphysema is related to elevated antibody titres against C. pneumoniae. METHODOLOGY: We measured antibody titres against C. pneumoniae using ELISA, and assessed the severity of emphysema by the percentage of low attenuation area (%LAA) using high resolution (HR) CT in patients with COPD and in non-smoking control subjects. RESULTS: The mean %LAA was 2.2% in non-smoking controls (n = 28) and 13.3% in COPD patients (n = 94). COPD patients with a high IgG antibody index to C. pneumoniae (> or =2.0, n = 42) had a significantly higher %LAA (16.8%) than those with a low IgG index (<2.0, n = 52) (10.6%, P = 0.01). In addition, COPD patients with a high IgA antibody index (> or =2.0, n = 46) had a significantly higher %LAA (15.9%) than those with a low IgA index (<2.0, n = 48) (10.9%, P = 0.048). COPD patients with a high IgA antibody index also had a significantly lower %DLco than that associated with a low IgA index (68.1% and 80.3%, respectively, P = 0.007). There were no significant differences in age, smoking index or FEV(1)/FVC between these groups. CONCLUSION: These results suggest that high antibody titres against C. pneumoniae are linked with the severity of emphysema on high resolution CT and decreased diffusing capacity to carbon monoxide.

High resolution CT and bronchial reversibility test for diagnosing COPD.

BACKGROUND: COPD is defined by airflow limitation that is not fully reversible and is associated with relevant risk factors. The diagnosis requires that other causes of chronic airflow limitation (CAL) be excluded. We assessed the diagnostic utility of high resolution thoracic CT (HRCT) and bronchodilator reversibility to assist in making a diagnosis of COPD. METHODOLOGY: We investigated 516 consecutive patients whose FEV1/FVC was less than 70% after inhalation of bronchodilator. HRCT was performed on all subjects and a final diagnosis was made only after 3 months of treatment and repeated spirometry. RESULTS: Of 516 cases, 54.3% had COPD, 19.8% had asthma plus emphysema, and 13.2% had chronic asthma. The remaining 12.7% of patients with CAL had diffuse panbronchiolitis, bronchiectasis, bronchiolitis obliterans, or other miscellaneous diseases. In these minor diseases HRCT was essential in making a definitive diagnosis. The sensitivities of emphysema on HRCT and of absence of bronchodilator response for the diagnosis of COPD were 81% and 90%, respectively, and the specificities of the tests were 57% and 37%, respectively. In addition, HRCT revealed considerable heterogeneity of COPD. Emphysema was not recognized on HRCT in 18.6% of COPD patients. HRCT also revealed that 17.5% of COPD patients had other pulmonary complications including lung fibrosis compatible with usual interstitial pneumonia in the lung bases. CONCLUSIONS: HRCT and the bronchial reversibility test had reasonable sensitivities but low specificities for diagnosing COPD. HRCT has some additional advantages in detecting heterogeneity and concomitant lung diseases in COPD.

[Usefulness of Streptococcus pneumoniae urinary antigen detection kit and the duration and intensity of reactivity with urinary antigen in patients with pneumonia].

We evaluated a rapid urinary antigen detection kit, Binax Now Streptococcus pneumoniae (Binax Inc., USA), which detects S. pneumoniae antigen in urine by immunochromatographic membrane assay, in 379 patients with presumptive pneumonia (total: 454 urine samples). S. pneumoniae antigen was detected in 64 (34%) of 188 patients. In all 64, pneumonia was diagnosed clinically, and there were 11 intense reactivity cases, 27 intermediate cases, and 26 weak cases. We found only two patients with positive sputum cultures for S. pneumoniae among 26 patients with weak reactivity to urinary antigen. The weak urinary antigen reactivity seems to include a false-positive result for S. pneumoniae pneumonia. There were five patients with negative results in whom S. pneumoniae was isolated (false-negative). We took intense and intermediate reactivity to be positive in order to diagnose pneumococcal pneumonia, and the kit showed a sensitivity of 72% and a specificity of 94% in 379 patients. The urinary antigen kit allowed us to diagnose 80% more patients with pneumococcal pneumonia than the use of conventional bacteriological diagnosis alone. There was no significant difference in the initial clinical characteristics, or in the severity of pneumonia among the three groups, according to the color intensity reached using the kit--weak, intermediate, and intense for the reactivity of urinary antigen. The duration of reactivity with S. pneumoniae urinary antigen did not correlate with the clinical characteristics or the severity of pneumonia. We concluded that S. pneumoniae urinary antigen detection kit is a useful adjunct to culturing for determining the etiology of pneumonia.