Shinobu Akagawa

Primary diffuse alveolar septal amyloidosis with multiple cysts and calcification

We report an extremely rare case of primary diffuse alveolar septal amyloidosis associated with multiple cysts and calcification. Development of multiple cysts may have resulted from fragile alveolar walls, as a consequence of amyloid deposition both on alveolar walls and around capillaries.

A nationwide epidemiological survey of chronic hypersensitivity pneumonitis in Japan

BACKGROUND In 1999, a Japanese epidemiological survey of chronic hypersensitivity pneumonitis (HP) showed that summer-type HP was the most prevalent variant of the disease. The number of reported cases of chronic HP has recently been increasing, and the clinical features of the disease seem to have changed. We conducted another nationwide epidemiological survey of chronic HP in Japan to determine better estimates of the frequency and clinical features of the disease. METHODS A questionnaire was sent to qualified hospitals throughout Japan, and data on cases of chronic HP diagnosed between 2000 and 2009 were collected. RESULTS In total, 222 cases of chronic HP from 22 hospitals were studied. Disease subtypes included bird-related HP (n=134), summer-type HP (n=33), home-related HP (n=25), farmers lung (n=4), isocyanate-induced HP (n=3), and other types (n=23). The median proportion of lymphocytes in bronchoalveolar lavage fluid was high (24.5%). The primary findings of computed tomography of the chest were ground-glass attenuation and interlobular septal thickening. Centrilobular fibrosis was the major pathological finding on examination of surgical lung biopsy specimens from 93 patients. The median survival time was 83 months. CONCLUSIONS The proportion of bird-related HP was higher than that in the previous epidemiological survey, and the proportions of isocyanate-induced HP and farmers lung were lower. A crucial step in diagnosing chronic HP is to thoroughly explore the possibility of antigen exposure.

Radiological features and therapeutic responses of pulmonary nontuberculous mycobacterial disease in rheumatoid arthritis patients receiving biological agents: a retrospective multicenter study in Japan

ObjectiveThis study was performed to evaluate the radiological features of and therapeutic responses to pulmonary disease caused by nontuberculous mycobacteria (NTM) in the setting of biological therapy for rheumatoid arthritis (RA).MethodsWe conducted a retrospective chart review of 13 patients from multiple centers who had developed pulmonary NTM disease during biological therapy for RA, including infliximab, etanercept, adalimumab, and tocilizumab.ResultsMost cases were asymptomatic or resulted in only common-cold-like symptoms. Abnormalities in computed tomography (CT) imaging were protean and frequently overlapped. The most predominant pattern was nodular/bronchiectatic disease (six cases), followed by alveolar infiltrate (three cases), cavitary disease (two cases), and pulmonary nodules (two cases). In most cases, pulmonary NTM disease had spread from a preexisting lesion; in particular, bronchial/bronchiolar abnormalities. In three cases, one or more nodular lesions with or without calcification were a focus of disease. Following the discontinuation of biological agents, most patients responded to anti-NTM therapy. Two patients showed no exacerbation in the absence of any anti-NTM therapy. In one patient, restarting tocilizumab therapy while continuing to receive adequate anti-NTM therapy produced a favorable outcome. In two other patients with a previous history of pulmonary NTM disease, introducing biological therapy led to recurrence, but anti-NTM therapy was effective in these patients.ConclusionCT abnormalities of pulmonary NTM disease in RA patients receiving biological therapy were variable, but were not unique to this clinical setting. NTM disease can spread from preexisting structural abnormalities, even if they are minute. Contrary to our expectations, the therapeutic outcomes of pulmonary NTM disease were favorable in these patients.

Tracheo-bronchitis as a complication of Crohn's disease —A case report—

A case of Crohns enterocolitis associated with diffuse tracheo-bronchitis is presented herein. Although respiratory tract involvement in Crohns disease is extremely rare, our review of the world literature revealed several common clinical pathologic features. These features include a productive cough with chest X-ray films which are normal except for some peripheral involvement. Bronchoscopy, however, shows diffuse inflammation of the trachea and bronchi with widely scattered whitish lesions while biopsy reveals a granulomatous infiltration of inflammatory cells. This tracheobronchitis typically responds well to treatment with prednisone.

Disseminated Mycobacterium avium complex infection in a patient carrying autoantibody to interferon-γ

A 66-year-old man was admitted to our hospital on suspicion of lung cancer with bone metastasis. He suffered multiple joint and muscle pain. 18F-Fluorodeoxy glucose positron emission tomography (FDG–PET) showed multiple accumulations in the lung, bones including the vertebrae, and mediastinal lymph nodes. Anti-human immunodeficiency virus (HIV) antibody was negative. Because Mycobacterium avium complex (MAC) was isolated from bronchial lavage fluid, bronchial wall, peripheral blood, and muscle abscess, he was diagnosed as having disseminated MAC infection. Although multidrug chemotherapy was initiated, his condition rapidly deteriorated at first. After surgical curettage of the musculoskeletal abscess, his condition gradually improved. As for etiology, we suspected that neutralizing factors against interferon-gamma (IFN-γ) might be present in his serum because a whole blood IFN-γ release assay detected low IFN-γ level even with mitogen stimulation. By further investigation, autoantibodies to IFN-γ were detected, suggesting the cause of severe MAC infection. We should consider the presence of autoantibodies to IFN-γ when a patient with disseminated NTM infection does not indicate the presence of HIV infection or other immunosuppressive condition.

Glucocorticoid Therapy and the Risk of Infection in Patients With Newly Diagnosed Autoimmune Disease.

AbstractGlucocorticoid (GC) therapy is associated with the risk of life-threatening adverse events in patients with autoimmune disease. To determine accurately the incidence and predictors of GC-related adverse events during initial GC treatment, we conducted a cohort study. Patients with autoimmune disease who were initially treated with GCs in Japan National Hospital Organization (NHO) hospitals were enrolled. Cox proportional hazard regression was used to determine the independent risks for GC-related serious adverse events and mortality. Survival was analyzed according to the Kaplan-Meier method and was assessed with the log-rank test.The 604 patients had a total follow-up of 1105.8 person-years (mean, 1.9 year per patient). One hundred thirty-six patients had at least 1 infection with objective confirmation, and 71 patients had serious infections. Twenty-two cardiovascular events, 55 cases of diabetes, 30 fractures, 23 steroid psychosis events, and 4 avascular bone necrosis events occurred during the follow-up period. The incidence of serious infections was 114.8 (95% confidence interval, 95.7–136.6) per 1000 person-years. After adjustment for covariates, the following independent risk factors for serious infection were found: elderly age (hazard ratio [HR], 1.25/10-yr age increment; p = 0.016), presence of interstitial lung disease (HR, 2.01; p = 0.011), high-dose GC use (≥29.9 mg/d) (HR, 1.71; p = 0.047), and low performance status (Karnofsky score, HR, 0.98/1-score increment; p = 0.002). During the follow-up period, 73 patients died, 35 of whom died of infection. Similarly, elderly age, the presence of interstitial lung disease, and high-dose GC use were found to be significant independent risk factors for mortality. The incidence of serious and life-threatening infection was higher in patients with autoimmune disease who were initially treated with GCs. Although the primary diseases are important confounding factors, elderly age, male sex, the presence of interstitial lung diseases, high-dose GCs, and low performance status were shown to be risk factors for serious infection and mortality.Abstract Glucocorticoid (GC) therapy is associated with the risk of life-threatening adverse events in patients with autoimmune disease. To determine accurately the incidence and predictors of GC-related adverse events during initial GC treatment, we conducted a cohort study. Patients with autoimmune disease who were initially treated with GCs in Japan National Hospital Organization (NHO) hospitals were enrolled. Cox proportional hazard regression was used to determine the independent risks for GC-related serious adverse events and mortality. Survival was analyzed according to the Kaplan-Meier method and was assessed with the log-rank test. The 604 patients had a total follow-up of 1105.8 person-years (mean, 1.9 year per patient). One hundred thirty-six patients had at least 1 infection with objective confirmation, and 71 patients had serious infections. Twenty-two cardiovascular events, 55 cases of diabetes, 30 fractures, 23 steroid psychosis events, and 4 avascular bone necrosis events occurred during the follow-up period. The incidence of serious infections was 114.8 (95% confidence interval, 95.7–136.6) per 1000 person-years. After adjustment for covariates, the following independent risk factors for serious infection were found: elderly age (hazard ratio [HR], 1.25/10-yr age increment; p = 0.016), presence of interstitial lung disease (HR, 2.01; p = 0.011), high-dose GC use (≥29.9 mg/d) (HR, 1.71; p = 0.047), and low performance status (Karnofsky score, HR, 0.98/1-score increment; p = 0.002). During the follow-up period, 73 patients died, 35 of whom died of infection. Similarly, elderly age, the presence of interstitial lung disease, and high-dose GC use were found to be significant independent risk factors for mortality. The incidence of serious and life-threatening infection was higher in patients with autoimmune disease who were initially treated with GCs. Although the primary diseases are important confounding factors, elderly age, male sex, the presence of interstitial lung diseases, high-dose GCs, and low performance status were shown to be risk factors for serious infection and mortality.

Nine pulmonary aspiration syndrome cases of atypical clinical presentation, in which the final diagnosis was obtained by histological examinations.

BACKGROUND While pulmonary aspiration syndrome (PAS) is primarily clinically diagnosed, atypical PAS cases can be misdiagnosed clinically and are more accurately diagnosed histologically. To elucidate clinicopathological features of these rare cases, we examined PAS cases determined by histological examination of transbronchial lung biopsy (TBLB) specimens. METHODS Of 6105 TBLB cases investigated from 1990 to 2007, 11 were diagnosed as PAS based on histology. Of these, we examined 9 records in detail, as the medical records for 2 cases were unavailable. RESULTS Histopathological findings indicated 8 patients with aspiration pneumonia and 1 with diffuse aspiration bronchiolitis. However, the pre-bronchoscopy diagnoses included lung cancer, mycobacteriosis, organizing pneumonia, repetitive pneumonia, fungal infection, and interstitial pneumonia. PAS was not considered before TBLB. Only 4 of the 9 patients developed subjective symptoms including fever and cough with sputum production. Laboratory findings demonstrated elevation of white blood cell (WBC) count in only 1 patient and elevation of C reactive protein (CRP) level in 4 patients. Radiographic examination revealed abnormal findings in the dorsal right lower lobes, which was the most vulnerable site for aspiration pneumonia, and also in the upper and ventral portions of the lung. Although the characteristic findings of PAS were scarce, all patients had conditions predisposing to aspiration; i.e., gastrectomy, excessive alcohol drinking, post-cerebral infarction, and sinobronchial syndrome. CONCLUSIONS We diagnosed 9 PAS patients on the basis of histological findings that were distinct from clinical findings. Despite presenting with variable symptoms and laboratory and radiographic findings, they all exhibited predisposing factors to aspiration.

Bronchial artery embolization to control hemoptysis in patients with Mycobacterium avium complex.

BACKGROUND Hemoptysis frequently develops in patients with Mycobacterium avium complex (MAC) pulmonary disease. Bronchial artery embolization (BAE) has been established as one of the useful treatments of massive and persistent hemoptysis. We evaluated the efficacy and safety of BAE for controlling hemoptysis in MAC patients, and identified the risk factors of rebleeding after BAE. METHODS Among the 529 patients with MAC who were admitted to our institution from January 2007 to December 2012, we retrospectively reviewed the demographic data, imaging, sputum, and angiographic findings, and the clinical course of 43 patients who underwent BAE using coils, due to hemoptysis. RESULTS Among the 43 patients enrolled in the study, rebleeding developed in 13 cases (30.2%) with a mean follow-up period of 18 months. Median rebleeding-free time after BAE was 29.9 months and the cumulative hemoptysis control rates were 79.1%, 73.8%, and 63.3% in one, two, and three years, respectively. Rebleeding-free time significantly correlated with comorbid chronic pulmonary aspergillosis (CPA). When limited to 35 MAC patients without CPA, the rate increased to 88.6%, 82.1%, and 70.4%, respectively. Factors such as coexisting CPA, multiple embolized vessels at BAE, longer length of time from the diagnosis of MAC to BAE, and an administration of antibiotics for MAC at the time of hemoptysis, indicated statistically significant correlations with rebleeding. Major complications concerning BAE were not encountered. CONCLUSIONS BAE using coils is an effective and safe method for controlling hemoptysis in patients with MAC pulmonary disease. However, it is important to carefully observe patients with risk factors for rebleeding after BAE.

Chronic pulmonary aspergillosis as a sequel to lobectomy for lung cancer

OBJECTIVES Chronic pulmonary aspergillosis (CPA) is an emerging complication after lobectomy for lung cancer. This retrospective study aimed to determine the incidence, main risk factors and clinical features of postoperative CPA in lung cancer patients. METHODS This study included lung cancer patients treated by lobectomy and with no previous history of thoracic surgery or coexistent aspergillosis at the time of surgery. The cumulative incidence of CPA was determined using death as a competing risk. Furthermore, the identified lung cancer patients were divided into CPA and non-CPA groups to compare their preoperative clinical features and to identify the risk factors of postoperative CPA by univariable and multivariable analyses. We also analysed the clinical features of CPA patients after diagnosis. RESULTS We included 475 lung cancer patients. Of these, 17 patients (3.6%) developed CPA after the lobectomy. The cumulative postoperative incidence rate of CPA was 2.3% [95% confidence interval (CI), 0.8-3.8%] at 5 years and 7.9% (95% CI, 3.0-13.0%) at 10 years. There were significantly more men (P = 0.007), smokers (P = 0.002) and comorbid chronic obstructive pulmonary disease (COPD) (P = 0.008) and interstitial lung disease (ILD) (P = 0.009) patients in the CPA group than in the non-CPA group. Multivariable analysis identified comorbid COPD (P = 0.0019) and ILD (P = 0.0003) as significant risk factors. An antifungal treatment response was obtained in 6 patients (35%). The 1-year survival rate was 47% (follow-up periods, interquartile range: 3-78 months), and 5 of the total of 11 deaths were due to CPA. CONCLUSIONS Through the present retrospective study, CPA seems to be a common sequel to lobectomy in lung cancer patients, and COPD and ILD represent strong risk factors of postoperative CPA. Because of the poor clinical outcome of lung cancer patients who develop CPA after lobectomy, careful follow-up using several examinations and chest radiographs to make CPA diagnosis may be essential.

Clinical and Angiographic Characteristics of 35 Patients With Cryptogenic Hemoptysis

BACKGROUND: Hemoptysis can cause a life‐threatening condition and often needs to be treated urgently. Nearly 20% of hemoptysis cases are diagnosed as cryptogenic after clinical investigation. The purpose of this study was to clarify the clinical and angiographic characteristics of cryptogenic hemoptysis. METHODS: We retrospectively reviewed medical records of 35 patients admitted to our hospital with cryptogenic hemoptysis from October 2010 to September 2014. RESULTS: In the 35 cases, bronchial artery embolization was successfully performed in 33 patients (94.3%), whereas bronchoscopic hemostatic therapy was added in one patient (2.8%), and embolization was not performed in one patient (2.8%) because the bronchial artery was too narrow. In the successful embolization group, the non‐rebleeding rate was 97.0% for 20 months. The angiographic findings revealed that the diameter of the bronchial arteries was < 2 mm in 13 patients, 2 to 3 mm in 17 patients, and > 3 mm in five patients. Hypervascularization was detected in 29 patients (82.9%) and small bronchial aneurysms in eight patients (22.9%). The amount of hemoptysis was slight (< 50 mL/d) in 12, mild (50–100 mL/d) in 11, moderate (100–200 mL/d) in eight, and massive (> 200 mL/d) in four patients. No obvious relationship was found between the diameter of bronchial arteries and the amount of hemoptysis. CONCLUSIONS: BAE was highly effective for the management of cryptogenic hemoptysis. Most cases of cryptogenic hemoptysis have angiographic abnormalities, including small or microaneurysms, which were suspected as the cause in some cases.