Prognostic significance of radiological pleuroparenchymal fibroelastosis in Mycobacterium avium complex lung disease: a multicentre retrospective cohort study.

BACKGROUND: Mycobacterium avium complex (MAC) causes chronic respiratory infectious diseases with diverse clinical features and prognoses. Pleuroparenchymal fibroelastosis (PPFE) is a rare disease characterised by pleural fibrosis with subjacent intra-alveolar fibrosis and alveolar septal elastosis, with unique chest high-resolution CT (HRCT) features (radiological PPFE). An association between recurrent respiratory infections and PPFE formation has been hypothesised; however, the clinical significance of PPFE in MAC lung disease remains unclear. METHODS: This retrospective, multicentre study investigated the prevalence of radiological PPFE in patients with MAC lung disease and its association with clinical features and outcomes. Radiological PPFE was diagnosed on the basis of HRCT findings. Prognostic factors were identified using Cox proportional hazards and Fine-Gray models. RESULTS: Of 850 consecutive patients with definite MAC lung disease, 101 (11.9%) exhibited radiological PPFE. Patients with radiological PPFE had unique characteristics, such as lower body mass index, lower survival rate (5-year cumulative survival rate, 63.1% vs 91.7%; p<0.001) and a higher incidence of respiratory-related death (5-year cumulative incidence, 31.1% vs 3.6%; p<0.001), than those without radiological PPFE. In the multivariable analysis, the presence of radiological PPFE was independently associated with all-cause mortality (adjusted HR, 4.78; 95% CI, 2.87 to 7.95; p<0.001) and respiratory-related death (adjusted HR, 3.88; 95% CI, 2.14 to 7.01; p<0.001). INTERPRETATION: This large-scale study demonstrated that in patients with MAC lung disease, radiological PPFE was common, a phenotype associated with unique clinical features and poor prognosis, particularly respiratory-related death. The specific management of this subgroup should be established.

Radiological and histopathological features and treatment response by subtypes of interstitial pneumonia with autoimmune features: A prospective, multicentre cohort study.

BACKGROUND: Patients with idiopathic interstitial pneumonia (IIP) have a favourable prognosis when they have interstitial pneumonia with autoimmune features (IPAF). However, precise IPAF-related findings from high-resolution computed tomography (HRCT) and lung histopathological specimens and the treatment response have not been fully determined. Therefore, this study was conducted to evaluate the relationship between findings on HRCT or lung histopathological specimens and the progression of interstitial pneumonia in patients with IPAF. METHODS: This multicentre cohort study prospectively enrolled consecutive patients with IIP. At the diagnosis of IIP, we systematically evaluated 74 features suggestive of connective tissue diseases and followed them up. HRCT, lung specimens, serum antibodies, and the clinical course were also evaluated. RESULTS: Among 222 patients with IIP, 26 (11.7%) fulfilled the IPAF criteria. During a median observation period of 36 months, patients with IPAF showed better survival than those without IPAF (p = 0.034). While histopathological findings were not related to IPAF, nonspecific interstitial pneumonia (NSIP) with organizing pneumonia (OP) overlap was the most prevalent HRCT pattern (p < 0.001) and the consolidation opacity was the most common radiological finding in IPAF (p = 0.017). Furthermore, in patients with IPAF, the diagnosis of COP or NSIP with OP overlap was associated with a higher increase in %FVC in 1 year than in those with idiopathic pulmonary fibrosis, NSIP, or unclassifiable IIP (p = 0.002). CONCLUSIONS: This study shows the presence of consolidation opacity on HRCT and the diagnosis of COP or NSIP with OP overlap are associated with IPAF and its favourable treatment response in patients with IPAF.

[Assessment of hand-foot syndrome in cancer patients treated with capecitabine-containing chemotherapy].

Capecitabine is one of the most effective oral chemotherapeutic drugs for advanced or recurrent colorectal cancer and gastric cancer. Capecitabine-containing chemotherapy is recommended as a first-line option for gastrointestinal tract cancer. The incidence of hand-foot syndrome (HFS), an adverse event of chemotherapy with capecitabine, is high. Moreover, once the symptoms of HFS are identified, they can significantly impair the quality of life (QOL) of patients. HFS should be managed by dose interruption and, if necessary, by dose reduction. Pharmacists and oncology nurses play an increasingly important role in the early identification and prevention of HFS through patient education and close clinical assessment. The aim of this study was to evaluate the efficacy of support tools for the early identification, prevention, and management of HFS and to assess the effectiveness of "patient self-check sheets". The patient was detected as having HFS of mild severity and had used a moisturizer at the time of initiation of therapy. Maintaining moisture retention is important in the management of HFS. The ambulatory team plays a key role by using self-check sheets to educate patients on how to recognize HFS, when to interrupt treatment, and how to adjust the dose so as to maintain effective therapy with capecitabine. For the continuation and completion of treatment and for maintaining an improved QOL in the home environment, supportive measures for adverse effects such as HFS and an ambulatory team are indispensable.

Pulmonary nocardiosis following nodular bronchiectatic Mycobacterium avium complex pulmonary disease in an immunocompetent patient.

A woman in her 70s with a history of nodular bronchiectatic Mycobacterium avium complex pulmonary disease (MAC-PD) presented with an exacerbated productive cough and worsening findings on chest imaging. Although repeated sputum culture tests were negative for acid-fast bacilli and only revealed normal respiratory flora, a bronchoscopy identified Nocardia sp. Consequently, she was diagnosed with pulmonary nocardiosis and was successfully treated with levofloxacin. It is known that pulmonary nocardiosis can manifest in immunocompetent individuals with bronchiectasis. For cases of refractory nodular bronchiectatic MAC-PD, it is vital to consider bronchoscopy to identify potential co-infections, such as Nocardia.

Healthcare workers' presenteeism causing an outbreak of respiratory infections in a facility for patients with severe motor and intellectual disabilities.

BACKGROUND: This study aimed to identify the source of infection and medical costs for a respiratory infection outbreak in a facility for patients with severe motor and intellectual disabilities (SMID). Presenteeism refers to a situation wherein a person continues going to work despite being ill. METHODS: The cohort included 1 healthcare worker and 17 patients who developed a fever of ≥37.5°C with respiratory symptoms for nearly a month. An outbreak investigation was conducted, which determined the initial case of the outbreak to be a single healthcare worker. We performed a univariate analysis to determine the association of the healthcare worker. From the medical records, we evaluated the costs of addition treatment and laboratory tests for the respiratory infection. RESULTS: The source of infection was a healthcare worker at the facility (Odds ratio, 17.5; 95% confidential interval, 3.0-101.8). The total medical cost for hospitalized patients due to this outbreak was $12,324. DISCUSSION: The source of a respiratory infection outbreak in a facility for SMID was suggested to be a healthcare worker's presenteeism. CONCLUSIONS: The cause of this outbreak was healthcare workers' presenteeism. To prevent outbreaks, such facilities should address the causative factors.

[Assessment of hand-foot syndrome in cancer outpatients undergoing chemotherapy].

Capecitabine, an oral prodrug of 5 -fluorouracil, is a promising treatment for colorectal, breast, and gastric cancers, but often causes hand-foot syndrome(HFS), which is the most common dose-limiting toxicity. The aim of this study was to evaluate of the efficacy of the pharmacist in providing support at ambulatory therapy centers, especially for HFS. The HFS is a higher-incidence adverse event that may develop during chemotherapy with capecitabine. Once developed, the symptoms significantly impair quality of life(QOL), leading to a reduction in the dosage or discontinuation of the treatment. Patient symptoms may therefore increase in severity. This study was performed to analyze the treatment adherence and adverse events resulting from capecitabine therapy provided by pharmacists to cancer outpatients. All patients were prescribed vitamin B6(pyridoxine), which can help to reduce or prevent HFS. A lesser or milder extent of HFS was detected in patients who had used a moisturizer at the same time as the introduction of capecitabine therapy. Adherence to this approach will benefit the patients' selfcare in maintaining moisture retention, which is an important countermeasure for HFS. Additionally, early introduction of effective countermeasures for skin care, dose reduction, and rest periods is important for HFS management; in addition, team care support is dispensable. Our support system may be useful for management strategies for HFS. We suggest that improved quality of lif e is needed in cancer outpatients being treated with chemotherapy.

Antigen avoidance and environmental inhalation challenge for successful diagnosis of fibrotic hypersensitivity pneumonitis mimicking idiopathic pulmonary fibrosis.

A 77-year-old man was initially diagnosed with idiopathic pulmonary fibrosis (IPF) and treated with anti-fibrotic nintedanib. Despite undergoing anti-fibrotic treatment for one year, his condition remained unstable. The patient was admitted to our hospital for exertional dyspnea. We performed an exposure assessment, including 2-week antigen avoidance and an environmental inhalation challenge, and successfully re-diagnosed him with fibrotic hypersensitivity pneumonitis (HP), known as chronic farmer's lung. Adding oral glucocorticoids to the nintedanib treatment improved his condition. Although antigen avoidance and environmental inhalation challenge tests are not standardized, they may be useful for diagnosing fibrotic HP when properly applied.

[A case of pulmonary-limited Wegener granulomatosis mimicking bacterial pneumonia caused by Staphylococcus aureus].

A 56-year-old woman who had suffered from systemic lupus erythematosus and Sjögren syndrome was admitted complaining of persistent cough. Chest X-ray films showed an infiltrative shadow in the right middle lung field. Her serum PR3-ANCA titer was high, and granulomatous inflammation with Langhans giant cell was noted in a transbronchial biopsy specimen. About 3 months later, purulent sputum and high grade fever developed, with a new infiltrative shadow in the left upper lung field noted on a chest X-ray film. We treated her based on a diagnosis of bacterial pneumonia caused by methicillin-resistant Staphylococcus aureus, but her condition did not improve. We finally gave her a diagnosis of pulmonary-limited Wegener's granulomatosis. Her condition improved with the administration of sulfamethoxazole-trimethoprim, prednisolone and cyclophosphamide. We report a case of pulmonary-limited Wegener granulomatosis which mimicked bacterial pneumonia caused by methicillin-resistant Staphylococcus aureus. This case suggests that Wegener's granulomatosis should be considered on encountering pneumonia caused by Staphylococcus aureus.

[Epithelioid angiomyolipoma of the kidney].

A 50-year-old male was referred to our hospital for a left renal mass which was incidentally found during a medical check-up. Abdominal ultrasonography, computed tomography, and magnetic resonance imaging showed a weak enhancement tumor devoid of fat densities at the lower pole of the left kidney. Under the diagnosis of renal cell carcinoma, radical nephrectomy was performed. Histopathological examination revealed large epithelioid cells, and immunohistochemical staining showed strongly positive for HMB-45. The patient was diagnosed with epithelioid angiomyolipoma of the kidney. Epithelioid angiomyolipoma is a rare variant of angiomyolipoma, which is sometimes occurred aggressive clinical behavior. However, our case remains without evidence of recurrence or metastasis after radical nephrectomy, and showed relatively better prognosis than in previous reports.

[A case of relapsing sarcoidosis with pleurisy 14 years after spontaneous remission].

An 83-year-old woman was referred to our hospital with dyspnea on exertion and right pleural effusion. At the age of 69, she had been given a clinical diagnosis of sarcoidosis due to uveitis, bilateral hilar lymphadenopathy, bilateral multiple nodular shadows on chest images, and serum angiotensin-converting enzyme (SACE) level elevation. Remission was spontaneous. The pleural effusion was exudative lymphocyte-rich. On thoracoscopy, the macroscopic appearance of the parietal pleura was telangiectasia without nodular lesions and the pleural biopsy specimens revealed non-caseating epitheloid cell granulomas whose cultures were negative for acid-fast bacilli and fungi. A tuberculin skin test and QFT-2G were negative, thus we diagnosed sarcoidsis pleurisy.

Macrolide resistant Mycobacterium avium complex pulmonary disease following clarithromycin and ethambutol combination therapy.

RATIONALE: Whether two-drug therapy (clarithromycin and ethambutol) for Mycobacterium avium complex (MAC) pulmonary disease contributes to the development of macrolide-resistant MAC is unclear. OBJECTIVE: To compare the incidence of macrolide-resistant MAC between patients treated with two-drug therapy (clarithromycin and ethambutol) and the standard three-drug therapy (clarithromycin, ethambutol, and rifampicin) for MAC pulmonary disease. METHODS: We retrospectively reviewed 147 patients with treatment-naive MAC pulmonary disease who had received two-drug therapy (n = 47) or three-drug therapy (n = 100) between 1997 and 2016 at National Hospital Organization, Tenryu Hospital, Hamamatsu, Japan. The risk of development of macrolide-resistant MAC was evaluated by calculating the cumulative incidence rate using Gray's test. RESULTS: The median follow-up period was 74.5 months. During the follow-up period, one of the 47 patients (2.1%) in the two-drug group developed macrolide-resistant MAC, compared to 12 of the 100 patients (12.0%) in the three-drug group. The cumulative incidence rate of macrolide-resistant MAC was lower in the two-drug group than in the three-drug group (0.0023; 95% confidence interval, 0.002 to 0.107 versus 0.200; 95% confidence interval, 0.100 to 0.324, p = 0.0593). CONCLUSIONS: These results suggest that two-drug treatment with clarithromycin and ethambutol for MAC pulmonary disease does not lead to a higher incidence of resistance acquisition to clarithromycin than the standard three-drug treatment.

Intravenous immunoglobulin therapy for refractory interstitial lung disease associated with polymyositis/dermatomyositis.

Interstitial lung disease (ILD) associated with polymyositis/dermatomyositis (ILD-PM/DM), including amyopathic dermatomyositis (ADM), is recognized as an important condition because it frequently causes death, despite intensive therapy with high-dose corticosteroid and immunosuppressive agents, such as cyclosporine A and cyclophosphamide. Intravenous immunoglobulin therapy (IVIG) has shown efficacy for myopathy associated with PM/DM, but its usefulness for ILD-PM/DM is unclear. This study was designed to investigate the efficacy of IVIG for refractory ILD-PM/DM. A review was made of medical charts of five patients (2 men and 3 women) who were treated with IVIG for refractory ILD-PM/DM resistant to high-dose corticosteroid and cyclosporine A and/or cyclophosphamide. One patient had acute ILD-PM and four patients had acute ILD-ADM. Of the five patients, one patient with ILD-PM and one patient with ILD-ADM survived. No adverse reactions were seen due to IVIG treatment. There were no critical differences in the clinical parameters and clinical courses between survivors and nonsurvivors. IVIG treatment is safe and could be an effective salvage therapy for refractory ILD-PM/DM in certain cases, suggesting that further controlled trials are worthwhile.

[A case of pulmonary infection caused by Pseudomonas aeruginosa with anorexia nervosa].

A 19-year-old woman with anorexia nervosa (body weight 25 kg) was admitted to our hospital, showing a cavitary shadow in the left upper lung field on a chest radiograph film. We diagnosed a pulmonary abscess caused by Pseudomonas aeruginosa. A few days later, exacerbation, including enlargement of the cavitary shadow, ipsilateral pleural effusion and bilateral infiltrations, were observed. Finally, by using antibiotics such as Doripenem (DRPM) and Ciprofloxacin (CPFX), we were able to treat the disease by bronchoscopic and thoracic drainage. This case suggests we should take carefully treat anorexia nervosa patients with pulmonary infection.

Body composition changes successfully classify prognosis in patients with mycobacterium avium complex lung disease.

OBJECTIVES: Loss of body weight, a manifestation of cachexia, is frequently found in patients with Mycobacterium avium complex lung disease (MAC-LD) and known as a prognostic determinant. However, the involvement of body composition changes in the prognosis of patients with MAC-LD remains unclear. METHODS: The cross-sectional-area of the erector spinea muscle (ESMCSA) and mean attenuation of the erector spinae muscles (ESMMA) in patients with MAC-LD, as determined by computed tomography imaging, were measured in two independent cohorts (137 and 111 patients, respectively). RESULTS: Patients with MAC-LD showed significantly smaller ESMCSA together with lower body mass index (BMI), but no difference in ESMMA in both cohorts compared with controls. Smaller ESMCSA, body mass index decline, and decreased ESMMA were associated with worse survival in the patients. Among them, decreased ESMMA showed prognostic significance in the multivariate analyses. Importantly, assessment by ESMMA together with BMI successfully divided the patients into three groups with distinct prognoses. CONCLUSION: Changes in body composition, especially decreased ESMMA, had prognostic significance in patients with MAC-LD. Additionally, combined assessment of ESMMA and BMI accurately predicted the prognosis of MAC-LD, which may be a helpful tool for disease management.

Alterations in smoking habits are associated with acute eosinophilic pneumonia.

BACKGROUND: Acute eosinophilic pneumonia (AEP) is characterized by a febrile illness, diffuse pulmonary infiltrates, and pulmonary eosinophilia. The etiology of AEP remains unknown, but several studies have proposed a relationship between cigarette smoking and AEP. However, most studies showing this possibility are single-case reports, and cigarette smoke has not been fully validated as a causative agent of AEP in a large series of patients. The present study was conducted to clarify the etiologic role of cigarette smoking in AEP, with special reference to alterations in smoking habits. METHODS: We took a detailed history of smoking habits before AEP onset in 33 patients with AEP, and performed a cigarette smoke provocation test. RESULTS: Of our AEP patients, all but one (97%) were current smokers. Interestingly, 21 of these were new-onset smokers, and 2 had restarted smoking after a 1- to 2-year cessation of smoking. The duration between starting smoking and AEP onset was within 1 month (0.67 +/- 0.53 months). Additionally, six of the remaining smokers had increased the quantity of cigarettes smoked daily, fourfold to fivefold, mostly within the month before AEP onset (0.81 +/- 0.58 months). Only three smokers had not changed their smoking habits before AEP onset. Cigarette smoke provocation tests revealed positive results in all nine patients tested. CONCLUSION: These data suggest that recent alterations in smoking habits, not only beginning to smoke, but also restarting to smoke and increasing daily smoking doses, are associated with the development of AEP.

Drug lymphocyte stimulation test in the diagnosis of adverse reactions to antituberculosis drugs.

BACKGROUND: Tuberculosis (TB) is a worldwide infectious disease. Recently, standard therapy has become very effective for treating patients with TB; however, as a result of this powerful regimen, serious side effects have become an important problem. The aim of this prospective study was to evaluate the usefulness of the drug lymphocyte stimulation test (DLST) to determine anti-TB drugs causing side effects. METHOD: Four hundred thirty-six patients with TB were admitted to our hospital for treatment between January 2002 and August 2007. DLST was performed in patients who had certain adverse drug reactions during TB treatment. The causative drug was identified by the drug provocation test (DPT). The tested drugs were mainly isoniazid (INH), rifampin (RIF), ethambutol (EMB) and pyrazinamide (PZA). RESULTS: Of 436 patients, 69 patients (15.8%) had certain adverse drug reactions to anti-TB drugs. Of the 261 agents that underwent the DLST and DPT, 28 agents (10.7%) in 20 patients (28.9%) were positive by DLST, and 67 agents (25.7%) in 46 patients (66.6%) were identified as causative drugs by DPT. The sensitivity of DLST was only 14.9% for all drugs (INH, 14.3%; RIF, 13.6%; EMB, 14.3%; PZA, 0%). CONCLUSIONS: DLST offers little contribution to the detection of causative agents in patients with adverse anti-TB drug reactions.

[A case of antiphospholipid syndrome associated with acute respiratory distress syndrome].

A 52-year old woman admitted to our hospital because of productive cough and dyspnea. Breathing room air arterial blood gases, revealed severe hypoxemia (P/F ratio 185 mmHg) and Chest CT showed diffuse ground glass opacities in both lung fields. Respiratory failure gradually improved after steroid pulse therapy, sivelestat sodium hydrate and antibiotics. However, a mosaic pattern attenuation in the lung parenchyma on Chest CT remained and ultrasonic cardiography showed dilation of right ventricle. Since the presence of V/Q mismatch in pulmonary perfusion and ventilation scintigrams and lupus anticoagulant were detected, we finally diagnosed acute respiratory distress syndrome (ARDS) and pulmonary thromboembolism (PTE) associated with antiphospholipid syndrome (APS). Therefore, this case reminded us that PTE and APS could cause ARDS.

Macrophage mannose receptor, CD206, predict prognosis in patients with pulmonary tuberculosis.

Tuberculosis (TB) remains a leading cause of fatal infectious disease. Accumulations of macrophages are found in infected sites; thus, we hypothesized that a marker of activated macrophages may be related to prognosis of pulmonary TB (PTB). This study investigated serum soluble macrophage mannose receptor, sCD206, in PTB and examined its clinical significance. First, the concentration of sCD206 was measured in the sera of 96 patients with PTB (Tenryu cohort), and in pleural effusions from 29 patients with TB pleurisy. These were verified in another independent cohort (Shizuoka cohort). We found increased concentrations of sCD206 in sera, but not in pleural effusions of PTB patients. Notably, PTB patients with poor prognosis showed significantly higher levels of serum sCD206. At a cut-off value of 1,600 ng/mL in the Tenryu cohort, sCD206 predicted prognosis of PTB with area under the curve 0.847, sensitivity 77.3%, and specificity 86.5%. These results were validated in the Shizuoka cohort. Pathological analyses showed concordance of enhanced CD206 expression in lung and pleural tissues with caseating granuloma in TB. Serum sCD206 increased in PTB and was associated with prognosis. sCD206 is a potential biomarker for PTB.

Utility of Macrophage-activated Marker CD163 for Diagnosis and Prognosis in Pulmonary Tuberculosis.

RATIONALE: Among infectious diseases, tuberculosis (TB) is a leading cause of death worldwide. Accumulated knowledge has revealed that macrophages are deeply involved in the progression and pathogenesis of TB. We hypothesized that the evaluation of a macrophage activation marker may be useful in the diagnosis and assessment of pulmonary TB. OBJECTIVES: To examine the utility of the macrophage activation marker soluble CD163 (sCD163) as a diagnostic tool and measure of disease severity for pulmonary TB and tuberculous pleurisy. METHODS: We compared the concentration of sCD163 in serum samples of 180 patients with active pulmonary TB with concentrations in serum samples of 45 age- and sex-matched control subjects. We also measured sCD163 in pleural fluid samples of 100 patients with pleural disease, including 31 patients with tuberculous pleurisy. MEASUREMENTS AND MAIN RESULTS: We found increased serum concentrations of sCD163 in patients with active pulmonary TB compared with those of control subjects (1,643 ± 1,737 ng/ml vs. 533.9 ± 49.3 ng/ml; P < 0.0001). sCD163 levels were also higher in pleural fluid samples of patients with pulmonary TB than in those of patients with non-TB pleurisy (5,239 ± 2,436 ng/ml vs. 2,877 ± 1,191 ng/ml; P < 0.0001). The levels of sCD163 in pleural effusions were significantly higher than serum levels obtained simultaneously from the same patients, particularly for patients with tuberculous pleurisy. Patients with a serum level of sCD163 above 1,300 ng/ml, had a mortality rate that was five times higher than that of patients with a lower sCD163 level (44.6% vs. 6.6%; P < 0.0001 by log-rank test). Microscopic examination of lung and pleural tissue samples showed concordance of enhanced CD163 expression with the presence of caseating granulomas in tissue obtained from patients with TB. CONCLUSIONS: The macrophage activation marker CD163 was increased in patients with active pulmonary TB compared with age- and sex-matched control subjects. Increased levels of sCD163 were associated with increased mortality in patients with pulmonary TB. sCD163 also showed promise as a diagnostic tool for tuberculous pleurisy. These results warrant further study of sCD163 as a potentially useful biomarker for the diagnosis and assessment of pulmonary TB. Clinical trial registered with www.umin.ac.jp/ctr/index-j.htm (UMIN000003400).

[A case of severe intestinal tuberculosis, treated with ciprofloxacin, kanamycin and prednisolone].

A 31-year-old man was admitted to our hospital because of frequent diarrhea. Colonoscopy showed ring ulcers on the rectum and ascending colon and chest X-ray showed abnormal shadows which were diagnosed as tuberculosis by sputum PCR. He started treatment with isoniazid (INH), rifampicin (RFP), pyrazinamide (PZA) and streptomycin (SM), however, eruption and ileus were seen. Then, he was retreated with ciprofloxacin (CPFX), kanamycin sulfate (KM) and prednisolone (PSL). Subsequently, we added RFP and further added calcium para-aminosalicylate (PAS). All these treatment was effective, and he was discharged from the hospital.