Search

Chronic eosinophilic pneumonia (CEP) is an idiopathic disorder characterised by an abnormal and marked accumulation of eosinophils in the interstitium and alveolar spaces of the lungs. Systemic corticosteroid (CS) therapy leads to marked improvement. However, relapse is common in the clinical course, and the predictive factors for relapse of CEP are not well known. This study aimed to investigate predictive factors for relapse in CS-treated cases of CEP.We identified consecutive patients with CEP at our institution between 1999 and 2019. We retrospectively reviewed 36 CS-treated patients with CEP who underwent bronchoalveolar lavage (BAL) and high-resolution computed tomography (CT) at diagnosis. We examined relapse at least 1 year after the initiation of CS treatment. Statistical analysis included univariate and multivariate Cox proportional hazard regression analyses; P0.05 was considered statistically significant.The median (interquartile range) age at diagnosis was 59.5 years (47.8-70.0 years). This study included 13 men and 23 women. Twenty-five patients (69.4%) were never smokers and 15 (41.7%) had asthma. The peripheral blood eosinophil percentage was 35.0% (15.6-55.8%), and the BAL eosinophil percentage was 40.8% (10.7-68.5%). The median serum surfactant protein-D (SP-D) level was 135 ng/mL (82.2-176.7 ng/mL). High-resolution CT revealed centrilobular opacities in 23 patients (63.9%). Relapse of CEP was observed in 20 patients (55.6%). Higher serum SP-D levels and the presence of centrilobular opacities on high-resolution CT were significant predictors of relapse in multivariate Cox proportional hazard regression analysis (P=0.017 and P=0.028, respectively). Additionally, we devised a relapse prediction model for CS-treated CEP using two categorical parameters: the presence of centrilobular opacities and serum levels of SP-D (135/≤135 ng/mL). Based on these parameters, cases were scored 2, 1, or 0. Patients with a score of 2 experienced relapses earlier than those with scores of 1 and 0 (log-rank test; P=0.006, P=0.003, respectively).Centrilobular opacities on high-resolution CT and higher serum SP-D levels at diagnosis may be predictive factors for relapse in CS-treated patients with CEP.

Airway-centered fibroelastosis is a distinct entity characterized by prominent airway-centered elastosis of the upper lobe with little or no pleural involvement. Little is known regarding its etiology; however, it was reported to have an idiopathic or asthma-associated etiology. We document, for the first time, 2 women (19 and 60 years old) who developed pleuroparenchymal fibroelastosis with a predominantly airway-centered distribution as a late complication (6 and 9 years later, respectively) of chemotherapy. The disease rapidly progressed following the manifestation of symptoms, and they subsequently died (3 and 2 years later, respectively). Therefore, post-chemotherapy long-term monitoring for this disease is warranted.

Background Autoimmune pulmonary alveolar proteinosis (APAP) results from the suppression of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling by a neutralizing autoantibody against GM-CSF. B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are involved in immunoglobulin G production and are overproduced in various autoimmune disorders. We hypothesized that BAFF and/or APRIL levels would be elevated in serum and bronchoalveolar lavage fluid (BALF) and serum and BALF levels of BAFF and APRIL respond to the treatments (whole lung lavage (WLL) or inhalation of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF)) in patients with APAP. Subjects and methods BAFF and APRIL levels in serum and BALF from 110 patients with APAP were measured at baseline and during and after treatment, using an enzyme-linked immunosorbent assay kit. We enrolled 34 healthy volunteers as serum cytokine controls, and 13 disease controls for BALF. Associations of BAFF and APRIL levels with clinical measures were assessed to clarify their clinical roles. Results In patients with APAP, serum BAFF and APRIL levels were significantly increased relative to healthy volunteers (p Conclusions BAFF and APRIL levels of sera and BALF in APAP were significantly increased compared with healthy volunteer and disease control, and the BAFF and APRIL pathway might have important specific roles in pathogenesis of APAP. Our data suggest a new perspective of future treatment for APAP.

Autoimmune pulmonary alveolar proteinosis (APAP) is caused by macrophage dysfunction due to anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody. We experienced 2 cases of APAP complicated with sarcoidosis in a 42-year-old woman and a 51-year-old man (age at the sarcoidosis diagnosis). APAP preceded sarcoidosis in the woman, and both diseases were diagnosed simultaneously in the man. Sarcoidosis lesions were observed in the lung, skin, and eyes, and the pathological findings of APAP were not marked at the diagnosis of sarcoidosis in either case. Low-grade positive serum anti-GM-CSF autoantibody was suspected to be correlated with the occurrence of sarcoidosis and resolution of APAP.

A 26-year-old man with a history of bronchial asthma was found to have high-density shadows along the bronchovascular bundle and in the subpleural area on computed tomography of the chest. Surgical lung biopsy specimens from the right S5 showed fibroelastosis in the subpleural and central airway area with alveolar destruction. He was diagnosed with airway-centered fibroelastosis of unknown cause after multidisciplinary discussions. The patient developed pulmonary hypertension and died 6 years later. The patient was younger in comparison to patients in earlier reports and had more obvious subpleural fibroelastic lesions in the upper lobes than in previously described cases.

BackgroundAcute exacerbation (AE) has been reported to herald a poor prognosis in idiopathic pulmonary fibrosis and is now thought to do so in idiopathic interstitial pneumonias (IIPs). However, the pathophysiology of AE-IIPs is not sufficiently understood. In our previously reported SETUP trial, we found better survival in patients with AE-IIPs treated with corticosteroids and thrombomodulin than in those treated with corticosteroids alone. In that study, we collected serum samples to evaluate changes in cytokine levels and retrospectively examined the prognostic significance and pathophysiological role of serum cytokines in patients with AE-IIPs.MethodsThis study included 28 patients from the SETUP trial for whom serial serum samples had been prospectively obtained. AE-IIPs were diagnosed using the Japanese Respiratory Society criteria. All patients were treated with intravenous thrombomodulin and corticosteroids from 2014 to 2016. Serum levels of 27 cytokines were measured using Bio-Plex. The high-resolution CT pattern at the time of diagnosis of AE was classified as diffuse or non-diffuse.ResultsUnivariate analysis revealed that higher serum levels of interleukin (IL)-2, IL-7, IL-9, IL-12, IL13, basic fibroblast growth factor, granulocyte-macrophage colony-stimulating factor, interferon-γ inducible protein-10, platelet-derived growth factor and regulated on activation, normal T cell expressed and secreted (RANTES) at AE were significant predictors of 90-day survival. The HRCT pattern was also a significant clinical predictor of 90-day survival. Multivariate analysis with stepwise selection identified a higher serum RANTES level at AE to be a significant predictor of 90-day survival, including after adjustment for HRCT pattern. Multivariate analysis with stepwise selection suggested that a marked increase in the serum IL-10 level on day 8 could predict 90-day mortality.ConclusionsA higher serum RANTES level at AE the time of diagnosis predicted a good survival outcome, and an elevated serum IL-10 level on day 8 predicted a poor survival outcome.Trial registration numberUMIN000014969.

Pulmonary veno-occlusive disease (PVOD) is a rare disease in the subgroup of conditions known as pulmonary arterial hypertension. Although a histological examination is needed for a definitive diagnosis, a non-invasive diagnosis is required for patients with pulmonary hypertension because a lung biopsy is deemed risky. We herein report a 32-year-old woman diagnosed with PVOD via a surgical lung biopsy and autopsy whose disease showed radiological findings mimicking those of hypersensitivity pneumonitis (pneumonia) at the time of the transbronchial lung biopsy, without obvious pulmonary hypertension on admission. When clinicians encounter patients with interstitial lung disease, they should not forget the possibility of PVOD and should be alert for emerging pulmonary hypertension.

Dendriform pulmonary ossification (DPO) is a rare condition characterized by metaplastic bone formation in the lung parenchyma. It has been reported to be often associated with primary lung diseases, such as usual interstitial pneumonia (UIP) or chronic aspiration of gastric acid; however, its clinical features and pathophysiology remain unclear, especially in idiopathic cases. We herein report five DPO cases, including three with an idiopathic origin. In all cases of idiopathic DPO, the pathological and radiological examinations showed localized pulmonary lesions suggesting inflammation or hemorrhaging.

Background Anti-granulocyte–macrophage colony-stimulating factor autoantibody (GMAb) has been recognized as a diagnostic biomarker for autoimmune pulmonary alveolar proteinosis (aPAP). The aims of this study were to know the incidence of increased level of serum GMAb in granulomatous lung diseases (sarcoidosis and hypersensitivity pneumonitis [HP]) and to clarify the role of GMAb. Consecutive individuals diagnosed with sarcoidosis (n = 92) and HP (n = 45) at National Hospital Organization Kinki-Chuo Chest Medical Center were retrospectively analyzed. We measured serum GMAb levels at the diagnosis. Cut-off values of GMAb discriminating aPAP (n = 110) from healthy controls (n = 31) were determined by receiver operating characteristic (ROC) curve analysis. We compared the clinical features of sarcoidosis and HP patients with GMAb levels above the cut-off value (“Elevated-GMAb”) with those of patients whose GMAb levels below the cut-off value (“Low-GMAb”). Radiological and pathological findings in elevated-GMAb patients were re-evaluated to elucidate the role of GMAb in granulomatous lung diseases. Results Analysis of ROC indicated a sensitivity and specificity of 100% at GMAb level of 3.33 μg/mL for discriminating aPAP from healthy controls (area under curve = 1.000, p Conclusions We demonstrated the percentage of elevated-GMAb sarcoidosis and HP patients who presented with several features suggestive of aPAP. Elevated-GMAb sarcoidosis and HP patients without definitive aPAP diagnosis may have subclinical or early-stage aPAP and may not necessarily indicate false positives. Upon diagnosis of sarcoidosis or HP, measurement of GMAb may be useful in detecting possible comorbidity of subclinical or early-onset aPAP.

Background We previously reported that high-resolution computed tomography (HRCT) patterns and certain serum marker levels can predict survival in patients with acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) and in those with idiopathic interstitial pneumonias (IIPs). The utility of serum marker changes before and during AE has not been previously evaluated. This study aimed to clarify whether changes in serum marker levels could improve the prognostic significance of HRCT patterns in patients with AE-IIPs. Methods Seventy-seven patients (60 males, 17 females) with AE-IIP diagnosed between 2004 and 2016 and whose serum Krebs von den Lungen (KL)-6 and surfactant protein (SP)-D levels were measured before and at the onset of AE were enrolled in this study. The HRCT pattern of each patient was classified as diffuse, multifocal, or peripheral. We examined the prognostic significance of the HRCT pattern, increased serum marker levels, and a combination of these parameters using Cox proportional hazard regression analysis. Results Fifty-three patients had IPF and 24 had non-IPF IIP. A serum KL-6 level that was increased compared with the level in the stable state (ΔKL-6/ST-KL-6: ≤0.211) was a significantly poor prognostic factor in patients with a multifocal pattern. Multivariate Cox analysis identified long-term oxygen therapy, a partial oxygen tension/fraction of inspired oxygen ratio ≤200 Torr, and an elevated SP-D level during a stable state to be significantly poor prognostic factors in all patients. A diffuse HRCT pattern was not a significant prognostic factor in an AE-IIP in multivariate analysis after adjustment; however, a multifocal pattern accompanying a ΔKL-6/ST-KL-6 ≤0.211 or a diffuse pattern was a significantly poor prognostic factor than a peripheral pattern or a multifocal pattern with ΔKL-6/ST-KL-6 >0.211. Conclusions Combining the HRCT pattern and the ΔKL-6/ST-KL-6 value can improve our ability to predict the survival of AE-IIP patients.

BackgroundDendriform pulmonary ossification (DPO) is a rare condition characterized by metaplastic bone formation in the lung parenchyma. DPO has been reported to be often associated with usual interstitial pneumonia (UIP) or chronic aspiration of gastric acid; however, DPO is believed to be a multifactorial disease, and its clinical features and pathophysiology remain unclear. This study aimed to reveal the novel clinical features and pathophysiology of DPO.MethodsThe pathology reports of consecutive cases diagnosed by surgical lung biopsy for diffuse lung diseases (DLDs) between April 1, 2000 and March 31, 2018 were reviewed retrospectively. Cases showing ossification in their specimens were subsequently reviewed and confirmed as calcified density lesions on CT scans. Besides the definite DPO cases, two DPO cases that involved surgical resection of the lung tumor were also included in the study. The clinical, radiological, and pathological features were analyzed.ResultsThree (0.96 %) out of 313 cases with DLDs were identified as cases of definite DPO. Taken together with the two DPO cases showing lung tumors, five DPO cases were analyzed. The patients were predominantly male, with a median age of 69 years. Four cases showed no smoking history. One patient had gastroesophageal reflux disease and UIP, and another had demonstrable hiatal hernia. Laboratory data were not remarkable. Pulmonary function at baseline was almost normal, and no significant decline was observed during the follow-up period. All cases showed interstitial fibrosis accompanied by ossifications. Intriguingly, the histological examination revealed intra-alveolar fibrosis and slight inflammatory cell infiltration, including new bone formation, corresponding to the consolidation on the CT scan in one case. In addition, consolidation, suspected to be caused by inflammation or hemorrhage, was also noted in two other DPO cases, namely in all of three idiopathic cases without UIP or risk factors for gastric acid aspiration.ConclusionsAll five DPO cases were indolent, indicating that the prognosis of DPO might be good. The pathological and radiological findings suggested the possible involvement of pulmonary inflammation and hemorrhage in the pathogenesis of DPO.

Two hundred and thirty-three individuals read chest x-ray images (CXR) in the Asian Intensive Reader of Pneumoconiosis (AIR Pneumo) workshop. Their proficiency in reading CXR for pneumoconiosis was calculated using eight indices (X1–X8), as follows: sensitivity (X1) and specificity (X2) for pneumoconiosis; sensitivity (X3) and specificity (X4) for large opacities; sensitivity (X5) and specificity (X6) for pleural plaques; profusion increment consistency (X7); and consistency for shape differentiation (X8). For these eight indices, one-way analysis of variance (ANOVA) and Scheffe’s multiple comparison were conducted on six groups, based on the participants’ specialty: radiology, respiratory medicine, industrial medicine, public health, general internal medicine, and miscellaneous physicians. Our analysis revealed that radiologists had a significant difference in the mean scores of X3, X5, and X8, compared with those of all groups, excluding radiologists. In the factor analysis, X1, X3, X5, X7, and X8 constituted Factor 1, and X2, X4, and X6 constituted Factor 2. With regard to the factor scores of the six participant groups, the mean scores of Factor 1 of the radiologists were significantly higher than those of all groups, excluding radiologists. The two factors and the eight indices may be used to appropriately assess specialists’ proficiency in reading CXR.

Purpose To assess inter-observer variability in identifying traction bronchiectasis on computed tomography (CT) using additional criteria for chronic fibrosing interstitial pneumonia. Methods Seven experts categorized CT image set representing 39 patients into three groups on the basis of the presence of traction bronchiectasis, using a three-point scale: 3-definitely/probably yes; 2-possibly yes; and 1-definitely/probably no. This scale served as a reference standard. The image set included cases of chronic fibrosing interstitial pneumonia, non-interstitial lung disease, and difficult-to-determine cases. Forty-eight observers similarly assessed the same image set, first according to the Fleischner Society definition, and second with additional criteria, in which traction bronchiectasis was observed exclusively in chronic fibrosing interstitial pneumonia. The agreement level between the reference standard and each observer's evaluation in each session was calculated using weighted kappa values which were compared between the two sessions using a paired t test. Results The mean weighted kappa value for all observers was significantly higher in the second reading session (mean 0.75) than in the first reading session (mean 0.62) (p < 0.001). Conclusion Inter-observer agreement in identifying traction bronchiectasis improves when using the additional criteria which specify chronic fibrosing interstitial pneumonia as the underlying disease.

A 34-year-old woman experiencing shortness of breath was referred to our hospital. The patient was diagnosed with sporadic lymphangioleiomyomatosis based on the observation of bilateral diffuse multiple thin-walled cysts on computed tomography of the chest, chylous effusion, elevated serum vascular endothelial growth factor-D levels and transbronchial biopsy findings. This patient was a hepatitis B virus (HBV) carrier. Treatment with 1 mg daily of sirolimus was started after HBV DNA was brought below the cut-off level using entecavir. Sirolimus was effective, as the chylous effusion resolved completely and the dyspnea improved. The sirolimus dosage was increased to 2 mg daily without causing HBV reactivation.

Background Lymphangioleiomyomatosis (LAM) and connective tissue diseases (CTDs) occur more frequently among women than men. We investigated the frequency of comorbid CTD and positive serum autoantibody findings in patients with LAM. Methods A total of 152 patients with LAM were prospectively and consecutively registered in the National Hospital Organization Kinki-Chuo Chest Medical Centre cohort. The clinical data were retrospectively analysed, and patients were categorised into the following three groups: a CTD group, a non-CTD-autoantibody-positive group, and a non-CTD-autoantibody-negative group. Results All patients were women. We identified five patients with comorbid CTDs (3.3%): Sjögren’s syndrome (SjS) (n = 3), systemic lupus erythematosus (n = 1), and rheumatoid arthritis (n = 1). One patient with SjS was also diagnosed with antiphospholipid antibody syndrome. The positive rate for anti nuclear antibody was 31.5% and 6.9% at dilution of 1:40 or higher, and those of 1:160 or higher, respectively. It tended to be lower in patients with LAM than in healthy women. The positive rate for anti-SS-A and anti-SS-B antibody was 7.9% and 1.8%, respectively. No significant differences in age, type of LAM, smoking status, serum vascular endothelial growth factor D level, respiratory function, treatment, or prognosis were observed among the three groups. Conclusions Comorbid CTDs, especially SjS, in LAM patients should be considered.

Herein, we report on a case of a 70-year-old man with a primary high-grade myxofibrosarcoma (MFS) in the anterior mediastinum. A computed tomography (CT) scan of the patient's chest revealed a heterogeneous mass lesion. On magnetic resonance imaging (MRI), the mass lesion exhibited heterogeneous low signal intensity with focal high signal intensity on T1-weighted images, and high signal intensity with cystic lesions on T2-weighted images. There were no signs of adipose tissue or calcification in the chest CT or MRI findings. Tumor resection was performed for the diagnosis and treatment. The resected mass was composed of myxoid and solid areas. The myxoid areas revealed atypical spindle cells with abundant myxoid matrix. The solid areas showed atypical spindle cell proliferation with numerous mitoses and multinucleated atypical cells. MDM2 gene amplification was not found in the tumor using fluorescent in situ hybridization method. Thus, the tumor was diagnosed as myxofibrosarcoma. Post-operative radiation therapy was administered to the mediastinum. However, the patient died from locally recurrent disease 1-year after surgery. Our case confirms the existence of MFS in the mediastinum and shows its poor prognosis and rapid progression.

BackgroundAcute exacerbation (AE) in idiopathic pulmonary fibrosis and other idiopathic interstitial pneumonias (IIPs) are poor prognostic events although they are usually treated with conventional therapy with corticosteroids and immunosuppressants. Previously, we demonstrated the safety and efficacy of recombinant human soluble thrombomodulin (rhTM) for AE-IIP in the SETUP trial. Here, we aimed to clarify the efficacy of rhTM for poor-prognosis cases of AE-IIP.MethodsIn this study, we included 85 patients, in whom fibrin degradation product (FDP)/d-dimer was evaluated at AE, from the 100 patients in the SETUP trial. The AE-IIP patients in the rhTM arm (n=39) were diagnosed using the Japanese criteria from 2014 to 2016 and treated with intravenous rhTM for 6 days in addition to the conventional therapy. The AE-IIP patients in the control arm (n=46) were treated with the conventional therapy without rhTM between 2011 and 2013. The subjects were classified into higher and lower FDP/d-dimer groups based on the Japanese Association for Acute Medicine Disseminated Intravascular Coagulation scoring system. A multivariate Cox proportional hazard regression analysis with stepwise selection was performed to reveal the prognostic factors of AE-IIP.ResultsWe developed a prognostic scoring system using two significant prognostic factors, higher FDP/d-dimer at AE and prednisolone therapy before AE, with 3 and 2 points assigned for each parameter, respectively. The prognostic scores ranged from 0 to 5. Survival of AE-IIP patients with a prognostic score=0 was significantly better than that of patients with score ≥2. Survival was improved with the rhTM therapy (pConclusionsTreatment with rhTM might improve survival in AE-IIP cases with poor prognoses.Trial registration numberUMIN000014969, date: 28 August 2014.

Idiopathic pleuroparenchymal fibroelastosis is an acceptable entity among IIPs and not as rare as previously reported http://ow.ly/I5NEz

The International Classification of High-Resolution Computed Tomography (HRCT) for Occupational and Environmental Respiratory Diseases (ICOERD) is used to screen and diagnose respiratory illnesses. Using univariate and multivariate analysis, we investigated the relationship between subject characteristics and parenchymal abnormalities according to ICOERD, and the results of ventilatory function tests (VFT). Thirty-five patients with and 27 controls without mineral-dust exposure underwent VFT and HRCT. We recorded all subjects' occupational history for mineral dust exposure and smoking history. Experts independently assessed HRCT using the ICOERD parenchymal abnormalities (Items) grades for well-defined rounded opacities (RO), linear and/or irregular opacities (IR), and emphysema (EM). High-resolution computed tomography showed that 11 patients had RO; 15 patients, IR; and 19 patients, EM. According to the multiple regression model, age and height had significant associations with many indices ventilatory functions such as vital capacity, forced vital capacity, and forced expiratory volume in 1 s (FEV1). The EM summed grades on the upper, middle, and lower zones of the right and left lungs also had significant associations with FEV1 and the maximum mid-expiratory flow rate. The results suggest the ICOERD notation is adequate based on the good and significant multiple regression modeling of ventilatory function with the EM summed grades.

Cryptogenic organizing pneumonia (COP) generally responds well to corticosteroids with a favorable outcome. Rare cases of organizing pneumonia are rapidly progressive. Yousem et al. studied pathologic predictors of idiopathic bronchiolitis obliterans organizing pneumonia/COP with an unfavorable prognosis. Beardsley and Rassl proposed the name fibrosing organizing pneumonia (FOP). A 74-year-old female non-smoker presented with a 2-week history of dry cough followed by dyspnea and a fever. The clinical course was fulminant, but we successfully performed bronchoscopy. After the diagnosis of FOP, we treated the patient with mechanical ventilation and high-doses of steroids/immunosuppressants, which improved the disease.

Objectives Evidence on the safety and long-term efficacy of super selective bronchial artery embolisation (ssBAE) using platinum coils in patients with haemoptysis is insufficient. The objective of the present study was to evaluate the safety and the 3-year postprocedure haemoptysis-free survival rate of de novo elective ssBAE using platinum coils rather than particles for the treatment of haemoptysis. Design A single-centre retrospective observational study. Setting Hemoptysis and Pulmonary Circulation Center in Japan. Participants A total of 489 consecutive patients with massive and non-massive haemoptysis who underwent de novo elective ssBAE without malignancy or haemodialysis. Interventions ssBAE using platinum coils. All patients underwent CT angiography before the procedure for identifying haemoptysis-related arteries (HRAs) and for procedural planning. Primary and secondary outcome measures The composite of the 3-year recurrence of haemoptysis and mortality from the day of the last ssBAE session. Each component of the primary end point and procedural success defined as successful embolisation of all target HRAs were also evaluated. Results The median patient age was 69 years, and 46.4% were men. The total number of target vessels was 4 (quartile 2–7), and the procedural success rate was 93.4%. There were 8 (1.6%) major complications: 1 aortic dissection, 2 symptomatic cerebellar infarctions and 5 mediastinal haematoma cases. The haemoptysis-free survival rates were estimated by the Kaplan-Meier analysis at 86.9% (95% CI 83.7% to 90.2%) at 1 year, 79.4% (74.8% to 84.3%) at 2 years and 57.6% (45.1% to 73.4%) at 3 years. Although not statistically significant by the adjusted analysis of variance with multiple imputation of missing variables, cryptogenic haemoptysis tended to show the most favourable outcome and non-tuberculous mycobacterium showed the worst outcome (adjusted p=0.250). Conclusions We demonstrated the safety and long-term efficacy of elective ssBAE using platinum coils and established that it can be a valuable therapeutic option for treating patients with haemoptysis.

Background Pulmonary nocardiosis is a rare but severe infection caused by Nocardia species. This study aimed at describing the clinical characteristics and prognosis of pulmonary nocardiosis. Methods An observational, retrospective study was undertaken of patients diagnosed with pulmonary nocardiosis over a 13-year period at the Kinki-Chuo Chest Medical Center, Osaka, Japan. Results Seven patients with airway nocardial colonization and 59 patients with pulmonary nocardiosis were identified, one of whom had disseminated nocardiosis. Patients with pulmonary nocardiosis were predominantly male patients (73%), with a mean age of 66 (range, 15–88) years. New-onset cough and dyspnea were the most common manifestations (76%). Although 52 (88%) patients had at least one underlying pulmonary disease, most patients did not appear to be systemically immunocompromised. The predominant abnormality on chest computed tomography in pulmonary nocardiosis was airspace consolidation (52%), sometimes associated with cavitation. Multivariate Cox proportional-hazards analysis revealed the following significant and independent risk factors for overall mortality: age >68 years (hazard ratio [HR], 4.7; 95% confidence interval [CI], 1.6–14; p =0.05), pulmonary aspergillosis (HR, 8.8; 95% CI, 2.4–33; p =0.01), and trimethoprim/sulfamethoxazole (TMP-SMZ) resistance (HR, 4.3; 95% CI, 1.6–11; p =0.04). Conclusions Clinicians should be aware that pulmonary nocardiosis can occur even in immunocompetent patients, especially those with an underlying pulmonary disease. In pulmonary nocardiosis, older age, pulmonary aspergillosis, and TMP-SMZ resistance are associated with increased risk of mortality.

Background Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with a poor prognosis. Recently, pirfenidone was reported to slow the rate of decline in vital capacity and improve progression-free survival in IPF. The purpose of this study was to clarify the factors that predicted a good response to pirfenidone, as well as its adverse effects. Methods Forty-one IPF cases, treated with pirfenidone from January 2009 to January 2011, were enrolled in this investigation. Disease severity was classified into grades I–IV, as defined by the Japanese Respiratory Society (JRS). Short-term responsiveness to pirfenidone was evaluated by the modified criteria of the JRS. Predictors of nausea, anorexia, or both that represented important adverse effects were examined by multivariate Cox proportional hazard analyses. Predictors of short-time responsiveness were examined by multivariate logistic regression analyses. Results Diagnosed by a surgical lung biopsy (SLB), the mild cases of grade I/II were predictors of good, short-term responsiveness. Patients taking acid-secretion inhibitors, including proton pump inhibitors and histamine H2-receptor antagonists, showed less anorexia, nausea, or both. Only 1 case was administered drugs to activate gastrointestinal motility. Conclusions We concluded that IPF patients with a mild disease, diagnosis by SLB, or both showed indications of a good response to pirfenidone. In addition, acid-secretion inhibitors may reduce the frequency of anorexia, nausea, or both from pirfenidone.

BackgroundIn lymphangioleiomyomatosis (LAM), tuberous sclerosis gene mutations activate the mechanistic target of the rapamycin pathway, resulting in vascular endothelial growth factor-D (VEGF-D) overproduction. While the utility of serum VEGF-D testing for the diagnosis of LAM is outlined in ATS/JRS LAM Guidelines, the assay has not been fully validated for Asian populations. Our aims were to validate serum VEGF-D testing in Japan, by directly comparing measurements in Japan and the U.S., determining the diagnostic cut-off for serum VEGF-D levels among the Japanese women with typical thin walled cystic change on CT, and determining the performance of VEGF-D as a prognostic biomarker.Subjects and methodsWe determined serum VEGF-D levels from 108 LAM patients, 14 disease controls, and 51 healthy volunteers from the Japanese population. Measurements of 61 LAM patients were compared to those from the principal VEGF-D laboratory in the U.S at Cincinnati Children's Hospital Medical Center. We correlated baseline serum VEGF-D levels with baseline and longitudinal clinical data to determine how pregnancy, sirolimus or gonadotrophin-releasing hormone (GnRH) agonists influence serum VEGF-D levels.ResultsSerum VEGF-D measurements in Japan and the U.S. were very similar. Baseline serum VEGF-D levels effectively distinguished LAM from other diseases and healthy volunteers at a cut-off level of 645 pg/ml and were diagnostically specific at 800 pg/ml, consistent with the recommendations of the ATS/JRS LAM Guidelines. Baseline serum VEGF-D correlated negatively with the DLco baseline % predicted and with the annual decrease in DLco % predicted. There was no significant association between baseline serum VEGF-D level and the outcomes of death or transplant. Serum VEGF-D levels markedly decreased during treatment with sirolimus, but not with GnRH analogues. Serum VEGF-D levels of most LAM patients did not increase over time, and neither pregnancy nor menopause significantly modulated serum VEGF-D levels.ConclusionsSerum VEGF-D is a useful diagnostic and therapeutic biomarker for LAM. Satisfactory precision and international inter-laboratory agreement of the clinical assay support VEGF-D recommendations in the ATS/JRS LAM Guidelines for the Japanese population.

Intramedullary spinal cord metastasis of non-small cell lung cancer is rare, and it has a short prognosis. We report a 53-year-old man diagnosed with cT4N0M0, stage IIIA squamous cell lung cancer. Ten months after left pneumonectomy (pT4N0M0), an intramedullary spinal cord tumor developed at the axis level. The intramedullary spinal cord tumor was resected, and he was diagnosed with metastatic squamous cell lung cancer. Radiotherapies and another tumor resection were conducted, as he had a good performance status and the discrete lesion was associated with the risk of brain stem compression. Multimodal local treatments for intramedullary spinal cord metastasis caused the tumor to shrink, and he lived for 25 months after the spinal metastasis occurred.

Background: The prognosis of combined cases of pulmonary fibrosis and emphysema is unresolved partially because radiological differentiation between usual interstitial pneumonia and nonspecific interstitial pneumonia is difficult in coexisting emphysema cases. Objective: The purpose of this study was to clarify the clinical impact of emphysema on the survival of patients with idiopathic pulmonary fibrosis (IPF). Methods: One hundred and seven patients with interstitial lung diseases were diagnosed by surgical lung biopsies between 2006 and 2012, and 47 patients were diagnosed with IPF through multidisciplinary discussion. Emphysema on high-resolution computed tomography scans was evaluated semiquantitatively by visual scoring. Results: Eight out of the 47 IPF patients showed a higher emphysema score (>3) and were diagnosed to have IPF-emphysema. The median survival time of patients with IPF-emphysema (1,734 days) from the initial diagnosis was significantly shorter than that of patients with IPF alone (2,229 days) by Kaplan-Meier analysis (p = 0.007, log-rank test). Univariate Cox proportional hazard regression analyses revealed that a higher total emphysema score (>3.0) was a significantly poor prognostic factor in addition to Krebs von den Lungen-6, surfactant protein-D, arterial oxygen tension, percent forced vital capacity, and percent diffusing capacity of carbon monoxide (%DLCO). Multivariate Cox proportional hazard regression analyses with the stepwise method showed that higher total emphysema score (>3) and %DLCO were significantly poor prognostic factors. Conclusions: The prognosis of IPF-emphysema was significantly worse than that of IPF alone.

The 60-film set was developed by experts (Expert Group) for examining 8 indices: sensitivity (X(1)) and specificity (X(2)) for pneumoconiosis, sensitivity(X(3)) and specificity for (X(4)) large opacities, sensitivity (X(5)) and specificity (X(6)) for pleural plaque, profusion increment consistency for small opacities (X(7)), and shape differentiation for small opacities (X(8)) of physicians' reading skills on pneumoconiosis X-ray according to ILO 2000 Classification. The aim of this study was to assess the appropriateness of the exam film set for evaluating physicians' reading skills. 29 physicians (A1-Group) and 24 physicians (A2-Group) attended the 1st and 2nd "Asian Intensive Reader of Pneumoconioses" (AIR Pneumo) training course, respectively, and 22 physicians (B-Group) attended Brazilian training course. After training, they took examination of reading 60-film exam set. The examinees' reading results in terms of 8 indices were compared between the examinee groups and the Expert Group by parametric unpaired t-test. The Examinee Group consisting of A1-Group, A2-Group and B-Group was inferior to the Expert Group in all indices. There was no significant difference for X(7) of A1-Group, X(7) and X(8) of A2-Group (p0.05) compared with the Expert Group. There was a significant difference in X(8) at p0.05 between A1-Group and A2-Group, in X(3) at p0.05 between A1-Group and B-Group, in both X(1) and in X(3) at p0.05 between A2-Group and B-Group. Accordingly, the 60-film set providing 8 indices designed might be a good method for evaluation of the physicians' reading proficiency at different training settings.

Rationale: Inhaled granulocyte/macrophage–colony stimulating factor (GM-CSF) is a promising therapy for pulmonary alveolar proteinosis (PAP) but has not been adequately studied. Objectives: To evaluate safety and efficacy of inhaled GM-CSF in patients with unremitting or progressive PAP. Methods: We conducted a national, multicenter, self-controlled, phase II trial at nine pulmonary centers throughout Japan. Patients who had lung biopsy or cytology findings diagnostic of PAP, an elevated serum GM-CSF antibody level, and a PaO2 of less than 75 mm Hg entered a 12-week observation period. Those who improved (i.e., alveolar–arterial oxygen difference [A–aDO2] decreased by 10 mm Hg) during observation were excluded. The rest entered sequential periods of high-dose therapy (250 μg Days 1–8, none Days 9–14; × six cycles; 12 wk); low-dose therapy (125 μg Days 1–4, none Days 5–14; × six cycles; 12 wk), and follow-up (52 wk). Measurements and Main Results: Fifty patients with PAP were enrolled in the study. During observation, nine improved and two withdrew; all of these were excluded. Of 35 patients completing the high- and low-dose therapy, 24 improved, resulting in an overall response rate of 62% (24/39; intention-to-treat analysis) and reduction in A–aDO2 of 12.3 mm Hg (95% confidence interval, 8.4–16.2; n = 35, P < 0.001). No serious adverse events occurred, and serum GM-CSF autoantibody levels were unchanged. A treatment-emergent correlation occurred between A–aDO2 and diffusing capacity of the lung, and high-resolution CT revealed improvement of ground-glass opacity. Twenty-nine of 35 patients remained stable without further therapy for 1 year. Conclusions: Inhaled GM-CSF therapy is safe, effective, and provides a sustained therapeutic effect in autoimmune PAP. Clinical trial registered with www.controlled-trials.com/isrctn (ISRCTN18931678), www.jmacct.med.or.jp/english (JMA-IIA00013).

Purpose: We have developed a classification of high-resolution computed tomography (HRCT) images for screening, surveillance and epidemiological studies of respiratory diseases caused by occupational and environmental factors. The proposed classification consists of three parts: a guideline explaining the elements of the classification scheme, a reading sheet, and reference films to aid in assessing thin-section CT films. We assessed the reliability of the proposed classification system by blinded, independent trial reading. Materials and Methods: Seven independent radiologists and pulmonologists performed a trial reading to measure the reliability of the classification system using HRCT films from 27 pneumoconiosis patients and 7 normal controls. Results: The agreement was moderate to good for rounded opacities (weighted κ=0.68 and 0.64), irregular opacities (0.59, 0.48), honeycombing (0.65, 0.47), emphysema (0.76, 0.62) and large opacities (0.48, 0.52). Ground glass opacities (0.16, 0.20) showed poor to fair agreement. Intra-reader agreement of each of the seven readers was moderate to good (mean: weighted κ=0.52-0.80) for parenchymal findings, but the agreement was relatively low (mean weighted κ=0.52) for ground glass opacities. Conclusion: The proposed classification is able to describe early dust-related fibrotic changes and provide a semi-quantitative description of the HRCT features of major fibrotic changes in the parenchyma and pleura. Reliability, as measured by inter-reader agreement, was satisfactory.

The International Classification of High-resolution Computed Tomography (HRCT) for Occupational and Environmental Respiratory Diseases (ICOERD) has been developed for the screening, diagnosis, and epidemiological reporting of respiratory diseases caused by occupational hazards. This study aimed to establish a correlation between readings of HRCT (according to the ICOERD) and those of chest radiography (CXR) pneumoconiotic parenchymal opacities (according to the International Labor Organization Classification/International Classification of Radiographs of Pneumoconioses [ILO/ICRP]). Forty-six patients with and 28 controls without mineral dust exposure underwent posterior-anterior CXR and HRCT. We recorded all subjects' exposure and smoking history. Experts independently read CXRs (using ILO/ICRP). Experts independently assessed HRCT using the ICOERD parenchymal abnormalities grades for well-defined rounded opacities (RO), linear and/or irregular opacities (IR), and emphysema (EM). The correlation between the ICOERD summed grades and ILO/ICRP profusions was evaluated using Spearman's rank-order correlation. Twenty-three patients had small opacities on CXR. HRCT showed that 21 patients had RO; 20 patients, IR opacities; and 23 patients, EM. The correlation between ILO/ICRP profusions and the ICOERD grades was 0.844 for rounded opacities (p

Summer-type hypersensitivity pneumonitis includes a spectrum of granulomatous lung diseases that result from the inhalation of Trichosporon species in the summer. Hot tub lung is a granulomatous lung disease caused by the inhalation of water aerosols containing non-tuberculous mycobacteria. We herein describe a case of hot tub lung that deteriorated during the winter season. Every winter, the patient's symptoms, laboratory findings and chest images worsened. Genetically identical Mycobacterium avium strains were detected in his sputum and bathtub. The circulation of bathtub water during the winter months only exacerbated his symptoms in the winter.

Correct diagnosis of diffuse cystic lung diseases is established in most cases by critical review of HRCT features http://ow.ly/NvrCc

A 52-year-old Japanese man with congenital amblyopia and oculocutaneous albinism was admitted to our hospital. Chest CT showed reticular opacities and traction bronchiectasis without honeycombing. Specimens obtained by a video-assisted thoracoscopic surgery showed patchy chronic fibrotic lesions. We diagnosed him with Hermansky-Pudlak syndrome (HPS). A mutation in the HPS1 gene was detected, and the diagnosis was confirmed. The patient was treated with prednisolone, pirfenidone, and azathioprine, but he nevertheless died within four months. Autopsy lung specimens showed diffuse alveolar damage suggesting comparatively rapid deterioration, although this presentation was not typical of an acute exacerbation. These pathological changes may be a possible progression pattern in HPS patients.

We report a case of serious complications following computed tomography (CT)-guided radiofrequency ablation (RFA) performed for the treatment of lung cancer with interstitial pneumonia. The patient developed delayed-onset pyopneumothorax, which required 6 months of antibiotic treatment, drainage, and video-assisted thoracoscopic debridement. Although CT-guided RFA is a promising, effective procedure for difficult-to-treat lung cancer, the present case suggests a risk of complications for patients complicated with interstitial pneumonia and warrants caution.

This study compared high-resolution computed tomography (CT) findings between 10 survivors and 21 nonsurvivors of acute interstitial pneumonia and evaluated whether the CT findings were predictive of patients' response to treatment. The survivor and nonsurvivor groups with pathologically or clinically diagnosed acute interstitial pneumonia were similar in age, sex, disease duration, and lung injury score. Retrospective, subjective evaluations of the CT scans were conducted by two independent observers without knowledge of patient outcomes. CT findings were graded on a one to six scale corresponding to consecutive pathologic phases as follows: areas of (1) normal attenuation, (2) ground-glass attenuation, (3) consolidation, (4) ground-glass attenuation associated with traction bronchiolectasis or bronchiectasis, (5) consolidation associated with traction bronchiolectasis or bronchiectasis, and (6) honeycombing. An overall score was obtained by quantifying the extent of each abnormality in three lung zones in each lung. The extent of ground-glass attenuation or consolidation associated with traction bronchiolectasis or bronchiectasis was less in survivors than nonsurvivors (p = 0.004 and p = 0.009, respectively). Architectural distortion was less frequent, and ground-glass attenuation or consolidation without traction bronchiolectasis or bronchiectasis was more extensive in survivors than in nonsurvivors (p = 0.007, p = 0.002, and p = 0.029, respectively). Overall CT scores of survivors were significantly lower than those of nonsurvivors (p = 0.0003). A CT score of less than 245 had an 80% positive and a 90% negative predictive value for survival. There was good interobserver agreement in the assessment of the CT findings (Kappa 0.75). The results indicate that CT assessment is potentially helpful in predicting patient prognosis in acute interstitial pneumonia regardless of the degree of physiologic abnormality.