Detection of fibrosing interstitial lung disease-suspected chest radiographs using a deep learning-based computer-aided detection system: a retrospective, observational study.

OBJECTIVES: To investigate the effectiveness of BMAX, a deep learning-based computer-aided detection system for detecting fibrosing interstitial lung disease (ILD) on chest radiographs among non-expert and expert physicians in the real-world clinical setting. DESIGN: Retrospective, observational study. SETTING: This study used chest radiograph images consecutively taken in three medical facilities with various degrees of referral. Three expert ILD physicians interpreted each image and determined whether it was a fibrosing ILD-suspected image (fibrosing ILD positive) or not (fibrosing ILD negative). Interpreters, including non-experts and experts, classified each of 120 images extracted from the pooled data for the reading test into positive or negative for fibrosing ILD without and with the assistance of BMAX. PARTICIPANTS: Chest radiographs of patients aged 20 years or older with two or more visits that were taken during consecutive periods were accumulated. 1251 chest radiograph images were collected, from which 120 images (24 positive and 96 negative images) were randomly extracted for the reading test. The interpreters for the reading test were 20 non-expert physicians and 5 expert physicians (3 pulmonologists and 2 radiologists). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the comparison of area under the receiver-operating characteristic curve (ROC-AUC) for identifying fibrosing ILD-positive images by non-experts without versus with BMAX. The secondary outcome was the comparison of sensitivity, specificity and accuracy by non-experts and experts without versus with BMAX. RESULTS: The mean ROC-AUC of non-expert interpreters was 0.795 (95% CI; 0.765 to 0.825) without BMAX and 0.825 (95% CI; 0.799 to 0.850) with BMAX (p=0.005). After using BMAX, sensitivity was improved from 0.744 (95% CI; 0.697 to 0.791) to 0.802 (95% CI; 0.754 to 0.850) among non-experts (p=0.003), but not among experts (p=0.285). Specificity and accuracy were not changed after using BMAX among either non-expert or expert interpreters. CONCLUSION: BMAX was useful for detecting fibrosing ILD-suspected chest radiographs for non-expert physicians. TRIAL REGISTRATION NUMBER: jRCT1032220090.

Programmed Death-Ligand 1-Positive Squamous Cell Carcinoma Spontaneously Regressed after Percutaneous Needle Biopsy.

Spontaneous lung cancer regression is a very rare course of disease. A 60-year-old male patient was admitted to our hospital with pneumonia and a 19 mm-sized nodule shadow in the S4 of the left lung on chest computed tomography (CT). A percutaneous needle biopsy was performed, and a diagnosis of programmed death-ligand 1-positive squamous cell lung carcinoma was made based on pathological findings. The patient was followed up with imaging because the lesion has reduced in size on chest CT. We report the possibility that cellular immune mechanisms triggered by needle biopsy contributed to spontaneous regression.

Deep-learning algorithm to detect fibrosing interstitial lung disease on chest radiographs.

BACKGROUND: Antifibrotic therapies are available to treat chronic fibrosing interstitial lung diseases (CF-ILDs), including idiopathic pulmonary fibrosis. Early use of these treatments is recommended to slow deterioration of respiratory function and to prevent acute exacerbation. However, identifying patients in the early stages of CF-ILD using chest radiographs is challenging. In this study, we developed and tested a deep-learning algorithm to detect CF-ILD using chest radiograph images. METHOD: From the image archive of Sapporo Medical University Hospital, 653 chest radiographs from 263 patients with CF-ILDs and 506 from 506 patients without CF-ILD were identified; 921 were used for deep learning and 238 were used for algorithm testing. The algorithm was designed to output a numerical score ranging from 0 to 1, representing the probability of CF-ILD. Using the testing dataset, the algorithm's capability to identify CF-ILD was compared with that of doctors. A second dataset, in which CF-ILD was confirmed using computed tomography images, was used to further evaluate the algorithm's performance. RESULTS: The area under the receiver operating characteristic curve, which indicates the algorithm's detection capability, was 0.979. Using a score cut-off of 0.267, the sensitivity and specificity of detection were 0.896 and 1.000, respectively. These data showed that the algorithm's performance was noninferior to that of doctors, including pulmonologists and radiologists; performance was verified using the second dataset. CONCLUSIONS: We developed a deep-learning algorithm to detect CF-ILDs using chest radiograph images. The algorithm's detection capability was noninferior to that of doctors.

Simultaneous Pseudoprogression and an Immune-related Adverse Event of Pulmonary Pleomorphic Carcinoma after Combined Therapy with Cytotoxic Anticancer Agents and Immune Checkpoint Inhibitor.

Pulmonary pleomorphic carcinoma is rare among lung tumors. Pulmonary pleomorphic carcinoma is resistant to chemotherapy. However, treatment with taxane anticancer agents and immune checkpoint inhibitors has been reported to be effective. When using immune checkpoint inhibitors, pseudoprogression and true progression are difficult to distinguish, and immune-related adverse events (irAEs) are common. We herein report a patient with simultaneous pseudoprogression and irAEs after combined therapy with cytotoxic agents and an immune checkpoint inhibitor for pulmonary pleomorphic carcinoma. Immune checkpoint inhibitors are effective against pulmonary pleomorphic carcinoma, but patients should be monitored for pseudoprogression and irAEs.

Prognostic value of 6-min walk stress echocardiography in patients with interstitial lung disease.

BACKGROUND: The 6-min walk test (6MWT) provides prognostic information for patients with interstitial lung disease (ILD). Parameter determined by Doppler echocardiography after the 6MWT (6 MW stress echocardiography) is shown to be a predictor of future development of pulmonary hypertension in patients with connective tissue disease. However, the clinical utility of 6 MW stress echocardiography in predicting cardiopulmonary events in patients with ILD remains unknown. We examined whether parameters determined by 6 MW stress echocardiography independent predictors of adverse events in patients with ILD. METHODS: Echocardiographic examinations were performed in 68 consecutively enrolled patients with ILD (age, 65 ± 10 years, 65% men). A pressure gradient of tricuspid regurgitation (TRPG) and pulmonary vascular resistance (PVRecho) calculated using the following formula [PVRecho = (peak velocity of TR × 10/time-velocity integral of right ventricular outflow (RVOT-VTI)) + 0.16] were measured at baseline and at post 6MWT. Data for parameters of pulmonary functional tests and for 6MWT were collected. RESULTS: During a mean follow-up period of 22 ± 12 months, 22 patients experienced cardiopulmonary events. In univariate analysis, %VC, TRPG, PVRecho, TRPG post 6MWT, and PVRecho post 6MWT were significantly associated with cardiopulmonary events. Multivariate analysis using the Cox proportional hazards model indicated that %VC [hazard ratio (HR): 0.97, p = 0.009] and PVRecho post 6MWT (HR: 1.77, p = 0.004) were independent predictors of cardiopulmonary events in patients with ILD. CONCLUSIONS: In addition to parameters of pulmonary function tests, increased PVRecho post 6MWT is a significant predictor of cardiopulmonary events in patients with ILD. A 6 MW stress echocardiography is useful in assessing the risk of adverse events in patients with ILD.

Serum surfactant protein D as a predictive biomarker for the efficacy of pirfenidone in patients with idiopathic pulmonary fibrosis: a post-hoc analysis of the phase 3 trial in Japan.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease course. The recent advancement of antifibrotic therapy has increased the need for reliable and specific biomarkers. This study aimed to assess alveolar epithelial biomarkers as predictors for the efficacy of the antifibrotic drug pirfenidone. METHODS: We conducted a post-hoc analysis of the prospective, multicenter, randomized, placebo-controlled, phase 3 trial of pirfenidone in Japan (total, n = 267; pirfenidone, n = 163; placebo, n = 104). Logistic regression analysis was performed to extract parameters that predicted disease progression, defined by a ≥ 10% relative decline in vital capacity (VC) from baseline and/or death, at week 52. For assessment of serum surfactant protein (SP)-D, SP-A and Krebs von den Lungen (KL)-6, all patients were dichotomized by the median concentration of each biomarker at baseline to the high and low biomarker subgroups. Associations of these concentrations were examined with changes in VC at each time point from baseline up to week 52, along with progression-free survival (PFS). Additionally, the effect of pirfenidone treatment on serial longitudinal concentrations of these biomarkers were evaluated. RESULTS: In the multivariate logistic regression analysis, body mass index (BMI), %VC and SP-D in the pirfenidone group, and BMI and %VC in the placebo group were indicated as predictors of disease progression. Pirfenidone treatment reduced the decline in VC with statistical significance in the low SP-D and low SP-A subgroups over most of the treatment period, and also prolonged PFS in the low SP-D and low KL-6 subgroups. Furthermore, SP-D levels over time course were reduced in the pirfenidone group from as early as week 8 until the 52-week treatment period compared with the placebo group. CONCLUSIONS: Serum SP-D was the most consistent biomarker for the efficacy of pirfenidone in the cohort trial of IPF. Serial measurements of SP-D might have a potential for application as a pharmacodynamic biomarker. Trial registration The clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC) on September 13, 2005 (registration No. JapicCTI-050121; http://Clinicaltrials.jp ).

A modified GAP model for East-Asian populations with idiopathic pulmonary fibrosis.

BACKGROUND: The easy-to-calculate gender, age, and lung physiology (GAP) model shows good predictive and discriminative performance in the prognosis of idiopathic pulmonary fibrosis (IPF). However, the GAP model was not effective in predicting the prognosis accurately in previous Japanese and Korean IPF cohort studies. Therefore, we developed a modified GAP model for the East-Asian populations by weighing the GAP variables. The validity of the modified GAP model was subsequently evaluated in East-Asian IPF patients. METHODS: The derivation cohort comprised 326 patients with IPF. Weights of the variables were adjusted on the basis of coefficients derived from Cox regression models. The total points were distributed to the three stages of the disease so that the number of patients included in each stage was appropriate. The validity of the modified model was analyzed in another Japanese cohort of 117 patients with IPF and a nationwide cohort of Korean patients with IPF. RESULTS: Predicted survival rates differed significantly in the derivation cohort using the modified GAP model for each stage of IPF (log-rank test: stage I vs. stage II, p < 0.001; stage II vs. stage III, p < 0.001). Model performance improved according to Harrell's C-index (at three years: 0.696 in the original GAP model to 0.738 in the modified model). The performance of the modified model was validated in the Japanese validation and Korean national cohorts. CONCLUSIONS: Our modification of the original GAP model showed improved performance in East-Asian IPF patient populations.

Correction to: Surfactant protein A as a biomarker of outcomes of anti-fibrotic drug therapy in patients with idiopathic pulmonary fibrosis.

Following publication of the original article [1], the authors have flagged that there is an error in Fig. 3.

Surfactant protein A as a biomarker of outcomes of anti-fibrotic drug therapy in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and fibrosing lung disease with poor prognosis. Pirfenidone and nintedanib are anti-fibrotic drugs used for patients with IPF. These drugs reduce the rate of decline in forced vital capacity (FVC). Serum surfactant protein (SP)-A, SP-D, and Krebs von den Lungen-6 (KL-6) are monitoring and prognostic biomarkers in patients with IPF; however, their relationship with the therapeutic outcomes of anti-fibrotic drugs has not been investigated. We aim to clarify whether serum SP-A, SP-D, and KL-6 reflect therapeutic outcomes of pirfenidone and nintedanib administration in patients with IPF. METHODS: We retrospectively investigated patients with IPF who were initiated on pirfenidone or nintedanib administration between January 2014 and June 2018 at our hospital. Changes in clinical parameters and serum SP-A, SP-D, and KL-6 levels were evaluated. Patients with ≥10% decline in FVC or ≥ 15% decline in diffusing capacity of the lung for carbon monoxide (DLco) from baseline to 6 months were classified as progression group, while the other patients were classified as stable group. RESULTS: Forty-nine patients were included (pirfenidone, 23; nintedanib, 26). Stable group comprised 32 patients, while progression group comprised 17 patients. In the stable group, changes in SP-A and KL-6 from baseline to 3 and 6 months significantly decreased compared with the progression group (SP-A: 3 months - 6.0% vs 16.7%, 6 months - 10.2% vs 20.2%, KL-6: 3 months - 9.2% vs 6.7%, 6 months - 15.0% vs 12.1%, p < 0.05). Changes in SP-A and SP-D levels showed significant negative correlations with the change in %FVC (r = - 0.46 and r = - 0.39, p < 0.01, respectively) and %DLco (r = - 0.67 and r = - 0.54, p < 0.01, respectively). Similar results were also seen in subgroup analysis for both pirfenidone and nintedanib groups. On logistic regression analysis, decrease in SP-A from baseline to 3 months and 6 months was found to predict the outcomes at 6 months (odds ratios: 0.89 and 0.88, respectively). CONCLUSIONS: Changes in serum SP-A reflected the outcomes of anti-fibrotic drug therapy. Serum SP-A has a potential as a biomarker of therapeutic outcomes of anti-fibrotic drugs.

A case of tracheal pleomorphic adenoma misdiagnosed as asthma.

A 51-year-old woman had an incidental finding of a tracheal tumor during oesophagogastroduodenoscopy following the diagnosis of asthma for 2 months. A computed tomography scan revealed a 15-mm tumor in the subglottis. Endoscopic resection was performed safely, and pleomorphic adenoma was diagnosed histologically. The patient's condition was satisfactory 30 months after the procedure. Tracheal pleomorphic adenoma is rare and may be misdiagnosed as asthma. If the tumor is large, surgery may be required; however, endoscopic polypectomy may be effective if the tumor is small. Therefore, early diagnosis of tracheal pleomorphic adenoma is important. At the first visit, the flow-volume curve suggested upper airway obstruction, which should have raised the suspicion of an upper airway obstruction. In patients with suspected asthma, early pulmonary function testing is needed to substantiate asthma diagnosis and prevent an alternative diagnosis being missed.

Insufficient serum L-ficolin is associated with disease presence and extent of pulmonary Mycobacterium avium complex disease.

BACKGROUND: The incidence of infectious disease caused by nontuberculous mycobacteria is increasing worldwide. Pulmonary Mycobacterium avium complex (MAC) disease is difficult to treat with chemotherapy, and its mechanism of infection, infection route, disease onset, and severity remain unknown. Ficolins are oligomeric defense lectins. L-ficolin plays an important role in innate immunity. This study's aim was to identify L-ficolin's role in patients with pulmonary MAC disease. METHODS: Between April 2011 and September 2017, 61 Japanese patients with pulmonary MAC disease were seen at our hospital. A control group, comprising 30 healthy individuals, without respiratory disease were enrolled in our study. The relationship between serum L-ficolin levels and disease severity was assessed, and L-ficolin's antibacterial role was examined. RESULTS: Serum L-ficolin levels were significantly lower in patients with pulmonary MAC disease than in healthy subjects (1.69 ± 1.27 µg/ml vs. 3.96 ± 1.42 µg/ml; p < 0.001). The cut-off value, based on receiver operating characteristic (ROC) analysis results, was 2.48 µg/ml (area under the curve (AUC) 0.90, sensitivity and specificity 83.6 and 86.7%, respectively). Serum L-ficolin levels were significantly lower in the patients with nodular bronchiectatic type disease compared with the patients with fibrocavitary type disease and were lower in the high-resolution computed tomography high-scoring group compared with low-scoring group. An in vitro analysis showed that purified recombinant L-ficolin bound to M. avium and its major cell wall component, lipoarabinomannan, in a concentration-dependent manner. In addition, recombinant L-ficolin suppressed M. avium growth in a concentration-dependent manner. CONCLUSIONS: Insufficient serum L-ficolin is associated with disease progression in pulmonary MAC disease, and the level of serum L-ficolin is a possible biomarker. TRIAL REGISTRATION: This study is registered with UMIN ( UMIN000022392 ).

Feasibility of rapid on-site cytological evaluation of lung cancer by a trained pulmonologist during bronchoscopy examination.

OBJECTIVE: Rapid on-site cytological evaluation (ROSE) in bronchoscopy is a useful ancillary technique. ROSE is usually performed by a cytopathologist or cytotechnologist. However, because of staff shortages and reduced availability, ROSE cannot be performed in every hospital. We aimed to evaluate the accuracy of ROSE when performed by a trained pulmonologist, comparing the diagnosis results with the final diagnosis of cytopathologists. METHODS: We performed a retrospective cohort study on 125 patients who underwent bronchoscopy with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endobronchial ultrasonography with a guide sheath (EBUS-GS) for peripheral pulmonary lesions by conventional bronchoscopy at Sapporo Medical University Hospital between March 2012 and September 2018. ROSE was performed by a pulmonologist who was trained by a cytotechnologist for a total of 1 month. DiffQuik® staining for ROSE was used to prepare cytology slides. The results of ROSE were compared with the final diagnosis obtained using Papanicolaou staining by cytopathologists. RESULTS: In all procedures, the sensitivity, specificity and diagnostic accuracy of ROSE were 88.5%, 83.0% and 86.4%, respectively. There was no significant difference in the sensitivity, specificity, positive predictive value, negative predictive value or accuracy between EBUS-TBNA and EBUS-GS. CONCLUSIONS: ROSE of lung cancer by a trained pulmonologist can be highly accurate and deemed as feasible and useful for not only EBUS-TBNA but also EBUS-GS.

Risk factors for acute exacerbation of idiopathic interstitial pneumonia in patients undergoing lung cancer treatment.

OBJECTIVE: Identifying risk factors for cancer treatment-related acute exacerbations (AEs) of idiopathic interstitial pneumonia (IIP) in patients with lung cancer. METHODS: We retrospectively reviewed clinical records of 98 patients with concurrent lung cancer and IIPs diagnosed and treated at the Sapporo Medical University Hospital from January 2010 to December 2014. RESULTS: Of the 98 patients with concurrent lung cancer and IIPs, 14 patients (14.3%) had AEs. A total of 10 patients died. The univariate analysis revealed that the patients with idiopathic pulmonary fibrosis (IPF) or usual interstitial pneumonia (UIP) patterns on chest computed tomography (CT) had significantly higher rates of AE than those with non-IPF or non-UIP patterns, respectively. Further, those with a reduced percentage of forced vital capacity (%FVC) predictive values or elevated Krebs von den Lungen-6 (KL-6) presented significantly higher rates of AE. Our multivariate analysis identified that UIP pattern on chest CT and each 10% decrease in %FVC were significant independent risk factors for AEs. Of the 14 patients who experienced AEs, 10 cases were associated with cancer treatment. The treatment-specific incidences were 3/40 (7.5%) for surgery, 5/50 (10.0%) for chemotherapy, and 2/26 (7.7%) for radiation therapy. After comparing the AE incidences in 55 cases receiving one treatment (monotherapy group) and in 29 cases receiving two types of treatment or more (multitherapy group), we found no significant differences. CONCLUSIONS: Chest CT UIP patterns and reduced %FVC are independent risk factors for AE. Moreover, AE incidence did not increase in the multitherapy group compared with the monotherapy group.

Autoimmune Pulmonary Alveolar Proteinosis Diagnosed after Exposure to a Fire Extinguisher Containing Silica Powder.

We herein report a case of autoimmune pulmonary alveolar proteinosis (PAP) diagnosed after one-time exposure to silica powder. Owing to the misuse of a silica-containing fire extinguisher and the inhalation of large amounts of its powder, the patient experienced prolonged cough and visited our hospital. The findings of chest computed tomography and surgical lung biopsy specimens led to the diagnosis of PAP. Interestingly, the presence of anti-GM-CSF antibody was detected; therefore, both autoimmune characteristics and exposure to large amounts of silica may have caused the development of PAP in this patient. This case provides important insight into the mechanisms leading to the onset of PAP.

Poorer Prognosis of Idiopathic Pleuroparenchymal Fibroelastosis Compared with Idiopathic Pulmonary Fibrosis in Advanced Stage.

Objective: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare disease characterized by predominant upper lobe pulmonary fibrosis of unknown etiology. However, the prognosis of IPPFE has not been discussed. We investigated the clinical characteristics and prognostic factors of IPPFE and idiopathic pulmonary fibrosis (IPF). Methods: We performed a retrospective cohort study on 375 consecutive idiopathic interstitial pneumonia patients between April 2004 and December 2014. Among them, we diagnosed IPPFE and IPF patients using high-resolution computed tomography radiological criteria. Results: Twenty-nine IPPFE patients (9 males, 20 females) and 67 IPF patients (54 males, 13 females) were enrolled. IPPFE patients were significantly more likely to be females and nonsmokers and had lower body mass index, lower values of predicted percentage of forced vital capacity (%FVC), and a higher residual volume-to-total lung capacity ratio than IPF patients. Survival analysis revealed that they had significantly poorer prognosis than IPF patients in GAP (gender, age, and physiology) stages II + III. %FVC and GAP index independently predict mortality in patients with IPPFE. Conclusions: Patients with IPPFE showed poorer prognosis in the advanced stage than patients with IPF. %FVC and GAP index are independent predictors of survival in patients with IPPFE.

Response to pneumococcal vaccine in interstitial lung disease patients: Influence of systemic immunosuppressive treatment.

BACKGROUND: Interstitial lung diseases (ILD) are severe respiratory diseases, and ILD patients are treated with corticosteroid and immunosuppressive agents. However, it is unclear whether these medications influence the response of pneumococcal vaccine. OBJECTIVES: We examined the immunogenicity of pneumococcal vaccines (PPSV23 and PCV13) in ILD patients undergoing immunosuppressive treatment. METHODS: ILD patients who were regularly followed at the outpatient clinic were enrolled. Sera were collected before and 4-8 weeks after vaccination. Serotype-specific immunoglobulin G (IgG) concentrations against pneumococcal serotype 19F were measured by ELISA. RESULTS: IgG concentrations to serotype 19F were increased in all groups in response to the vaccine. Both PCV13 and PPSV23 induced IgG concentrations in patients immunized for the first time. Response rates for the ILD group were comparable with those for the ILD group undergoing corticosteroid therapy. Only idiopathic pulmonary fibrosis patients undergoing immunosuppressive therapy had a significantly lower response.

Impaired diversity of the lung microbiome predicts progression of idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most frequent and severe form of idiopathic interstitial pneumonias. Although IPF has not been thought to be associated with bacterial communities, recent papers reported the possible role of microbiome composition in IPF. The roles of microbiomes in respiratory functions and as clinical biomarkers for IPF remain unknown. In this study, we aim to identify the relationship between the microbial environment in the lung and clinical findings. METHODS: Thirty-four subjects diagnosed with IPF were included in this analysis. The 16S rDNA was purified from bronchoalveolar lavage fluid obtained at the time of diagnosis and analyzed using next-generation sequencing techniques to characterize the bacterial communities. Furthermore, microbiomes from mice with bleomycin-induced lung fibrosis were analyzed. RESULTS: The most prevalent lung phyla were Firmicutes, Proteobacteria and Bacteroidetes. Decreased microbial diversity was found in patients with low forced vital capacity (FVC) and early mortality. Additionally, the diversity and relative abundance of Firmicutes, Streptococcaceae, and Veillonellaceae were significantly associated with FVC, 6-min walk distance, and serum surfactant protein D. Bleomycin-induced lung fibrosis resulted in decrease of diversity and alteration of microbiota in PCoA analysis. These results support the observations in human specimens. CONCLUSIONS: This study identified relationships between specific taxa in BALF and clinical findings, which were also supported by experiments in a mouse model. Our data suggest the possibility that loss of microbial diversity is associated with disease activities of IPF.

Serum surfactant protein D predicts the outcome of patients with idiopathic pulmonary fibrosis treated with pirfenidone.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal pulmonary disease with poor prognosis. Pirfenidone, the first antifibrotic drug, suppresses the decline in forced vital capacity (FVC) and improves prognosis in some, but not all, patients with IPF; therefore, an indicator for identifying improved outcomes in pirfenidone therapy is desirable. This study aims to clarify whether baseline parameters can be predictors of disease progression and prognosis in patients with IPF treated with pirfenidone. METHODS: We retrospectively investigated patients with IPF who started treatment with pirfenidone between December 2008 and November 2014 at the Sapporo Medical University Hospital. Patients treated with pirfenidone for ≥6 months were enrolled in this study and were observed until November 2015. We investigated the association of clinical characteristics, pulmonary function test results, and blood examination results at the start of pirfenidone with the outcome of patients. RESULTS: Sixty patients were included in this study. In multivariate logistic regression analysis, % predicted FVC and serum surfactant protein (SP)-D levels were predictors of a ≥10% decline in FVC in the initial 12 months. In the Cox proportional hazards model, these two factors predicted progression-free survival. Pack-years, % predicted diffusing capacity for carbon monoxide, and SP-D levels predicted overall survival. CONCLUSIONS: The serum SP-D level was a predictor of disease progression and prognosis in patients with IPF treated with pirfenidone. In addition, this analysis describes the relative usefulness of other clinical parameters at baseline in estimating the prognosis of patients with IPF who are candidates for pirfenidone therapy.

Volatile Organic Compounds in Exhaled Breath of Idiopathic Pulmonary Fibrosis for Discrimination from Healthy Subjects.

Purpose Human breath analysis is proposed with increasing frequency as a useful tool in clinical application. We performed this study to find the characteristic volatile organic compounds (VOCs) in the exhaled breath of patients with idiopathic pulmonary fibrosis (IPF) for discrimination from healthy subjects. Methods VOCs in the exhaled breath of 40 IPF patients and 55 healthy controls were measured using a multi-capillary column and ion mobility spectrometer. The patients were examined by pulmonary function tests, blood gas analysis, and serum biomarkers of interstitial pneumonia. Results We detected 85 VOC peaks in the exhaled breath of IPF patients and controls. IPF patients showed 5 significant VOC peaks; p-cymene, acetoin, isoprene, ethylbenzene, and an unknown compound. The VOC peak of p-cymene was significantly lower (p < 0.001), while the VOC peaks of acetoin, isoprene, ethylbenzene, and the unknown compound were significantly higher (p < 0.001 for all) compared with the peaks of controls. Comparing VOC peaks with clinical parameters, negative correlations with VC (r =-0.393, p = 0.013), %VC (r =-0.569, p < 0.001), FVC (r = -0.440, p = 0.004), %FVC (r =-0.539, p < 0.001), DLco (r =-0.394, p = 0.018), and %DLco (r =-0.413, p = 0.008) and a positive correlation with KL-6 (r = 0.432, p = 0.005) were found for p-cymene. Conclusion We found characteristic 5 VOCs in the exhaled breath of IPF patients. Among them, the VOC peaks of p-cymene were related to the clinical parameters of IPF. These VOCs may be useful biomarkers of IPF.

[THE CURRENT SITUATION OF FOREIGN TUBERCULOSIS PATIENTS AND THEIR CONCURRENT HIV INFECTION IN HOKKAIDO].

BACKGROUND AND PURPOSE: According to recent news, patients with concurrent tuberculosis (TB) and human immunodeficiency virus (HIV) infection are increasingly common worldwide. This study aimed to investigate whether TB/HIV co-infected patients are visiting Hokkaido. METHOD: We conducted a questionnaire survey regarding foreign patients infected with TB or TB/HIV who visited Hokkaido between January 2001 and September 2014. We mailed questionnaires to health centers, AIDS treatment care hospitals, and TB hospitals in Hokkaido prefecture. RESULTS: Seventy-one TB patients were of foreign nationality according to the answers obtained from health centers. Most of them were foreign students or occupational trainees between 20-30 years old. Approximately half these patients were from East Asia, and 7 patients were from Africa. As 21 % of the patients with TB who visited medical examination were over 1 month from disease onset, and the delay in visiting was recognized. The TB infection was mostly detected coincidentally during the physician visit. In the hospital survey, four TB patients with HIV were of foreign nationality. They were also of the age group from 20-30 years and hailed from sub-Saharan Africa. DISCUSSION: During immigration, medical examination by performing a chest radiograph is important. If the immigrant hails from an area where TB and HIV co-infection is common, it is necessary to confirm whether HIV infection is present.