Radiofrequency ablation in patients with interstitial lung disease and lung neoplasm: a retrospective multicenter study.

PURPOSE: To retrospectively investigate the safety and efficacy of percutaneous radiofrequency ablation (RFA) by analyzing results in patients with lung neoplasm accompanied by interstitial lung disease (ILD) on computed tomography (CT) in a multicenter study. MATERIALS & METHODS: Patients with lung neoplasm accompanied by ILD who underwent RFA between April 2002 and October 2017 at seven institutions were investigated. Technical success rate, and local tumor progression (LTP) of ablated tumors were evaluated. Adverse events including acute exacerbation of ILD were also evaluated. Univariate analyses were performed to identify factors associated with acute exacerbation. RESULTS: Forty-nine patients with 64 lung neoplasm (mean diameter, 22.6 mm; range, 4-58 mm) treated in 66 sessions were included. Usual interstitial pneumonia (UIP) pattern on CT was identified in 23 patients (47%). All patients underwent successful RFA. Acute exacerbations were seen in 5 sessions (8%: 7% with UIP pattern, 8% without) in 5 patients, all occurring on or after 8 days (median, 12 days; range, 8-30 days). Three of those 5 patients died of acute exacerbation. Treatment resulted in mortality after 5% of sessions, representing 6% of patients. Pleural effusion and fever ≥38°C after RFA were identified by univariate analysis (p = 0.0012, p = 0.02, respectively) as significant risk factors for acute exacerbation. The cumulative LTP rate was 43% at 1 year. CONCLUSIONS: RFA appears feasible for patients with lung neoplasm complicated by ILD. Acute exacerbation occurred in 8% of patients with symptoms occurring more than 8 days post-ablation and was associated with a 45% mortality rate.

Contrast defect of left atrial appendage on computed tomography is associated with higher risk of recurrence after catheter ablation in patients with paroxysmal atrial fibrillation.

The previous study has shown that the contrast defect of the left atrial appendage (LAA) on contrast-enhanced cardiac computed tomography (CT) is associated with a higher rate of stroke in patients with atrial fibrillation (AF). This study aimed to investigate the association between LAA CT contrast defect and the risk of arrhythmia recurrence after catheter ablation (CA) in patients with paroxysmal AF. A total of 283 paroxysmal AF patients [age: 67 ± 10 years, 185 (65%) males] who underwent cardiac CT before CA were retrospectively analyzed. The presence or absence of LAA CT contrast defect was visually assessed using early phase CT images. Recurrence was an episode of atrial arrhythmia beyond the first 90 days post-ablation. LAA flow velocity was measured using transesophageal echocardiography in 246 paroxysmal AF patients. Sixty-eight (24%) patients had an LAA CT contrast defect. LAA flow velocity was significantly reduced in patients with LAA CT defect compared to those without (56.8 ± 28.7 cm/s vs. 41.1 ± 19.1 cm/s, p < 0.001). During a median follow-up period of 858 days, arrhythmia recurrence was identified in 85 (30%) patients. On a Kaplan Meier curve, patients with LAA CT contrast defect had significantly higher recurrence rates than those without (p = 0.043). On a multivariable Cox regression analysis, LAA CT contrast defect was a significant and independent predictor after adjustment of age, sex and left atrial volume index (hazard ratio: 1.79, 95% confidence interval: 1.03-3.07, p = 0.036). LAA CT contrast defect was associated with decreased LAA flow velocity and a higher rate of arrhythmia recurrence after CA, suggesting its usefulness as a non-invasive predictor for high-risk AF patients resistant to CA therapy.

Acute Exacerbation and Proposed Criteria for Progressive Pulmonary Fibrosis in Patients with Fibrotic Hypersensitivity Pneumonitis and Idiopathic Pulmonary Fibrosis.

BACKGROUND: Acute exacerbation (AE) occasionally develops in the course of fibrotic hypersensitivity pneumonitis (HP). OBJECTIVE: The aim of the study was to compare AE of fibrotic HP with that of idiopathic pulmonary fibrosis (IPF). METHODS: Consecutive patients with pathologically confirmed fibrotic HP and IPF diagnosed based on a multidisciplinary discussion were included in the analysis. AE in patients with fibrotic HP and IPF was evaluated retrospectively. RESULTS: This study included 309 and 160 patients with fibrotic HP and IPF, respectively. Their 50% survival times were 96.1 and 78.0 months, respectively (hazard ratio [HR]: 0.54 [95% confidence interval, CI: 0.36-0.77], log-rank test; p < 0.001). Notably, the cumulative AE rates of fibrotic HP were 3% at 1 year and 10% at 3 years. Moreover, the corresponding rates of IPF were 8% at 1 year and 20% at 3 years (HR: 0.66 [95% CI: 0.45-0.93], log-rank test; p = 0.034). The 90-day survival rates from the AE onset of fibrotic HP and IPF were 75% and 64%, respectively (HR: 0.51 [95% CI: 0.31-0.83], log-rank test; p = 0.006). The respiratory function test on the physiological criteria of progressive pulmonary fibrosis (PPF) was a predictor of AE in fibrotic HP. However, the high-resolution CT (HRCT) changes in the criteria of PPF were not. Nevertheless, both the physiological and radiological criteria of PPF were a predictor of AE of IPF. CONCLUSION: AE of fibrotic HP has a lesser prognostic effect than that of IPF. HRCT criteria for PPF were not a risk factor for AE in patients with fibrotic HP.

Syndrome of Combined Pulmonary Fibrosis and Emphysema: An Official ATS/ERS/JRS/ALAT Research Statement.

Background: The presence of emphysema is relatively common in patients with fibrotic interstitial lung disease. This has been designated combined pulmonary fibrosis and emphysema (CPFE). The lack of consensus over definitions and diagnostic criteria has limited CPFE research. Goals: The objectives of this task force were to review the terminology, definition, characteristics, pathophysiology, and research priorities of CPFE and to explore whether CPFE is a syndrome. Methods: This research statement was developed by a committee including 19 pulmonologists, 5 radiologists, 3 pathologists, 2 methodologists, and 2 patient representatives. The final document was supported by a focused systematic review that identified and summarized all recent publications related to CPFE. Results: This task force identified that patients with CPFE are predominantly male, with a history of smoking, severe dyspnea, relatively preserved airflow rates and lung volumes on spirometry, severely impaired DlCO, exertional hypoxemia, frequent pulmonary hypertension, and a dismal prognosis. The committee proposes to identify CPFE as a syndrome, given the clustering of pulmonary fibrosis and emphysema, shared pathogenetic pathways, unique considerations related to disease progression, increased risk of complications (pulmonary hypertension, lung cancer, and/or mortality), and implications for clinical trial design. There are varying features of interstitial lung disease and emphysema in CPFE. The committee offers a research definition and classification criteria and proposes that studies on CPFE include a comprehensive description of radiologic and, when available, pathological patterns, including some recently described patterns such as smoking-related interstitial fibrosis. Conclusions: This statement delineates the syndrome of CPFE and highlights research priorities.

Concordance between transbronchial lung cryobiopsy and surgical lung biopsy for interstitial lung disease in the same patients.

BACKGROUND: The diagnostic accuracy and safety of transbronchial lung cryobiopsy (TBLC) via a flexible bronchoscope under sedation compared with that of surgical lung biopsy (SLB) in the same patients is unknown. METHODS: Retrospectively the data of fifty-two patients with interstitial lung diseases (median age: 63.5 years; 21 auto-antibody positive) who underwent TBLC followed by SLB (median time from TBLC to SLB: 57 days) was collected. The samples from TBLC and SLB were randomly labelled to mask the relationship between the two samples. Diagnosis was made independently by pathologists, radiologists, and pulmonary physicians in a stepwise manner, and a final diagnosis was made at multidisciplinary discussion (MDD). In each diagnostic step the specific diagnosis, the diagnostic confidence level, idiopathic pulmonary fibrosis (IPF) diagnostic guideline criteria, and treatment strategy were recorded. RESULTS: Without clinical and radiological information, the agreement between the histological diagnoses by TBLC and SLB was 42.3% (kappa [κ] = 0.23, 95% confidence interval [CI]: 0.08-0.39). However, the agreement between the TBLC-MDD and SLB-MDD diagnoses and IPF/non-IPF diagnosis using the two biopsy methods was 65.4% (κ = 0.57, 95% CI: 0.42-0.73) and 90.4% (47/52), respectively. Out of 38 (73.1%) cases diagnosed with high or definite confidence at TBLC-MDD, 29 had concordant SLB-MDD diagnoses (agreement: 76.3%, κ = 0.71, 95% CI: 0.55-0.87), and the agreement for IPF/non-IPF diagnoses was 97.4% (37/38). By adding the pathological diagnosis, the inter-observer agreement of clinical diagnosis improved from κ = 0.22 to κ = 0.42 for TBLC and from κ = 0.27 to κ = 0.38 for SLB, and the prevalence of high or definite diagnostic confidence improved from 23.0% to 73.0% and from 17.3% to 73.0%, respectively. Of all 383 TBLC performed during the same period, pneumothorax occurred in 5.0% of cases, and no severe bleeding, acute exacerbation of interstitial lung disease, or fatal event was observed. CONCLUSIONS: TBLC via a flexible bronchoscope under deep sedation is safely performed, and the TBLC-MDD diagnosis with a high or definite confidence level is concordant with the SLB-MDD diagnosis in the same patients.

Frequency of subclinical interstitial lung disease in COVID-19 autopsy cases: potential risk factors of severe pneumonia.

Risk factors of severe coronavirus disease 2019 (COVID-19) have been previously reported; however, histological risk factors have not been defined thus far. The aim of this study was to clarify subclinical hidden interstitial lung disease (ILD) as a risk factor of severe pneumonia associated with COVID-19. We carefully examined autopsied lungs and chest computed tomography scanning (CT) images from patients with COVID-19 for interstitial lesions and then analyzed their relationship with disease severity. Among the autopsy series, subclinical ILD was found in 13/27 cases (48%) in the COVID-19 group, and in contrast, 8/65 (12%) in the control autopsy group (p = 0.0006; Fisher's exact test). We reviewed CT images from the COVID-19 autopsy cases and verified that subclinical ILD was histologically detectable in the CT images. Then, we retrospectively examined CT images from another series of COVID-19 cases in the Yokohama, Japan area between February-August 2020 for interstitial lesions and analyzed the relationship to the severity of COVID-19 pneumonia. Interstitial lesion was more frequently found in the group with the moderate II/severe disease than in the moderate I/mild disease (severity was evaluated according to the COVID-19 severity classification system of the Ministry of Health, Labor, and Welfare [Japan]) (moderate II/severe, 11/15, 73.3% versus moderate I/mild, 108/245, 44.1%; Fisher exact test, p = 0.0333). In conclusion, it was suggested that subclinical ILD could be an important risk factor for severe COVID-19 pneumonia. A benefit of these findings could be the development of a risk assessment system using high resolution CT images for fatal COVID-19 pneumonia.

Atezolizumab for Pretreated Non-Small Cell Lung Cancer with Idiopathic Interstitial Pneumonia: Final Analysis of Phase II AMBITIOUS Study.

BACKGROUND: Interstitial pneumonia (IP) is a poor prognostic comorbidity in patients with non-small cell lung cancer (NSCLC) and is also a risk factor for pneumonitis. The TORG1936/AMBITIOUS trial, the first known phase II study of atezolizumab in patients with NSCLC with comorbid IP, was terminated early because of the high incidence of severe pneumonitis. METHODS: This study included patients with idiopathic chronic fibrotic IP, with a predicted forced vital capacity (%FVC) of >70%, with or without honeycomb lung, who had previously been treated for NSCLC. The patients received atezolizumab every 3 weeks. The primary endpoint was the 1-year survival rate. RESULTS: A total of 17 patients were registered; the median %FVC was 85.4%, and 41.2% had honeycomb lungs. The 1-year survival rate was 53.3% (95% CI, 25.9-74.6). The median overall and progression-free survival times were 15.3 months (95% CI, 3.1-not reached) and 3.2 months (95% CI, 1.2-7.4), respectively. The incidence of pneumonitis was 29.4% for all grades, and 23.5% for grade ≥3. Tumor mutational burden and any of the detected somatic mutations were not associated with efficacy or risk of pneumonitis. CONCLUSION: Atezolizumab may be one of the treatment options for patients with NSCLC with comorbid IP, despite the high risk of developing pneumonitis. This clinical trial was retrospectively registered in the Japan Registry of Clinical Trials on August 26, 2019, (registry number: jRCTs031190084, https://jrct.niph.go.jp/en-latest-detail/jRCTs031190084).

Prognostic impact of HNF4α expression in interstitial lung disease.

Pneumocyte injury is a crucial factor influencing the severity of interstitial lung disease (ILD). In this study, we investigated the potential of hepatocyte nuclear factor α (HNF4α) as an immunohistochemical marker to detect pneumocyte injury and as a prognostic marker. Surgical lung biopsy specimens were collected from 309 patients with different types of ILDs (61 idiopathic pulmonary fibrosis (IPF), 173 non-IPF, and 75 unclassifiable ILD). HNF4α expression were examined and the frequency of positive cells (per mm2 ) was calculated. HNF4α was strongly expressed in regenerating pneumocytes present on fibroblastic foci, Masson bodies/organizing alveoli. In the non-IPF and unclassifiable ILD groups, cases with high frequency expression showed significantly poorer outcome. Particularly, in the unclassifiable ILD group, the prognostic impact was more significant (death due to ILD, log-rank test, p < 0.0001), with a 10-year survival rate (hazard ratio 11.1, Wald test, p = 0.0003), as compared to the non-IPF group (log-rank test, p = 0.0269; hazard ratio 2.7, Wald test, p = 0.0334). Multivariable analysis focusing on the unclassifiable ILD group confirmed that the frequent HNF4α expression was an independent prognostic factor (hazard ratio 28.6; Wald test, p = 0.0033). Thus, HNF4α can be utilized as an immunohistochemical marker for pneumocyte injury and have prognostic impact particularly in unclassifiable ILD.

Native T1 heterogeneity for predicting reverse remodeling in patients with non-ischemic dilated cardiomyopathy.

A recent study has shown that the heterogeneity of native T1 mapping may be a new prognostic factor for patients with non-ischemic dilated cardiomyopathy (NIDCM). This study aimed to investigate the predictive value of native T1 heterogeneity of the left ventricular (LV) myocardium, as assessed by pixel-wise histogram analysis, for predicting left ventricular reverse remodeling (LVRR) by medical therapy in patients with NIDCM. A total of one hundred and thirteen NIDCM patients (mean age: 63 ± 12 years; 91 males and 22 females; mean LV ejection fraction (EF): 37 ± 10%) were retrospectively analyzed. T1 mapping images were acquired using a modified look-locker inversion recovery (MOLLI) sequence. We performed histogram analysis of native T1 mapping of LV myocardium, mean (T1-mean) and standard deviation (T1-STD) of native T1 time from each pixel were calculated. Extracellular volume fraction (ECV) was also evaluated. LVRR was defined as LVEF increased ≥ 10% points and decrease in LV end-diastolic volume ≥ 10% at 12 months from initiation of medical therapy. Cutoff value of T1-mean and T1-STD was set as median value of each parameter. Sixty (53%) NIDCM patients reached LVRR. Area under the receiver-operating characteristics curve for predicting LVRR was 0.763 (95% confidence interval (CI) 0.679-0.847) for %LGE, 0.757 (95% CI 0.663-0.850) for T1-mean, 0.724 (95% CI 0.625-0.823) for T1-STD, 0.800 (95% CI 0.717-0.882) for ECV, respectively. Proportion of LVRR was significantly lower in NIDCM patients with high T1-mean and high T1-STD (12%) compared to NIDCM with high T1-mean and low T1-STD (65%) (p < 0.001). Adding T1-STD to T1-mean improved AUC from 0.757 to 0.806, comparable to AUC of ECV. Combination of T1-mean and T1-STD, a parameter of heterogeneity of native T1 of the LV myocardium, may be a useful for prediction of LVRR by medical therapy without use of gadolinium contrast for patients with NIDCM.

Outcome of COVID-19 in interstitial lung disease patients treated with anti-inflammatory drugs and antiviral drugs.

A recent study reported that patients with interstitial lung disease (ILD) are at increased risk of death from coronavirus disease 2019 (COVID-19). However, there are no studies on the outcome of COVID-19 patients with preexisting ILD treated with corticosteroids or antiviral drugs. We extracted 26 patients with preexisting ILD by medical records and HRCT pattern. Of 503 patients with COVID-19, we selected 52 patients as control matched for age and sex. Twenty out of the 26 ILD patients (76.9%) received corticosteroid therapy, and 23 patients (88.5%) also received antiviral treatment with remdesivir or favipiravir. Although no statistical difference was found, the proportion of severe patients in ILD group tended to be higher than in non-ILD group (23.1% vs. 42.3%; p = 0.114). Also, mortality rate in ILD group tended to be higher than in non-ILD patients (11.5% vs. 3.8%; p = 0.326). In univariate analysis to evaluate risk factors for severe condition, diagnosis of idiopathic pulmonary fibrosis, usual interstitial pneumonia pattern, and honeycomb lung were not risk factors of severe disease. Treatment with corticosteroids, antiviral drugs, and immunosuppressive agents may affect the outcome of COVID-19 patients with ILD.

The new useful high-resolution computed tomography finding for diagnosing fibrotic hypersensitivity pneumonitis: "hexagonal pattern": a single-center retrospective study.

BACKGROUND: Centrilobular nodules, ground-glass opacity (GGO), mosaic attenuation, air trapping, and three-density pattern were reported as high-resolution computed tomography (HRCT) findings characteristic of fibrotic hypersensitivity pneumonitis (HP). However, it is often difficult to differentiate fibrotic HP from idiopathic pulmonary fibrosis (IPF). In fibrotic HP, the HRCT sometimes shows tortoiseshell-like interlobular septal thickening that extends from the subpleural lesion to the inner layers. This finding is called "hexagonal pattern," and this study is focused on the possibility that such finding is useful for differentiating fibrotic HP from IPF. METHODS: This study included patients with multidisciplinary discussion (MDD) diagnosis of fibrotic HP or IPF undergoing surgical lung biopsy between January 2015 and December 2017 in Kanagawa Cardiovascular and Respiratory Center. Two radiologists have evaluated the HRCT findings without clinical and pathological information. RESULTS: A total of 23 patients were diagnosed with fibrotic HP by MDD and 48 with IPF. Extensive GGO, centrilobular nodules, and hexagonal pattern were more frequent findings in fibrotic HP than in IPF. No significant difference was observed between the two groups in the presence or absence of mosaic attenuation, air trapping, or three-density pattern. In the multivariate logistic regression, the presence of extensive GGO and hexagonal pattern was associated with increased odds ratio of fibrotic HP. The sensitivity and specificity of the diagnosis of fibrotic HP in the presence of the hexagonal pattern were 69.6% and 87.5%, respectively. CONCLUSION: Hexagonal pattern is a useful finding for differentiating fibrotic HP from IPF.

Usefulness and safety of transbronchial lung cryobiopsy for reassessment of treatment in the clinical course of diffuse parenchymal lung disease.

BACKGROUND: The usefulness and safety of transbronchial lung cryobiopsy (TBLC) for reassessment of diffuse parenchymal lung disease (DPLD) with progression is still unknown. Our purpose was to clarify the usefulness and safety of TBLC for reassessment of DPLD with progression. METHODS: This retrospective study included 31 patients with DPLD diagnosed by surgical lung biopsy who progressed in the clinical course and underwent TBLC for reassessment between January 2017 and September 2019 at Kanagawa Cardiovascular & Respiratory Center. Two pulmonologists independently selected the clinical diagnosis, treatment strategy, and confidence level of the treatment strategy based on clinical and radiological information with and without pathological information from TBLC. A consensus was reached among the pulmonologists regarding the clinical diagnosis, treatment strategy, and confidence level of the treatment strategy. Complications of TBLC were also examined. RESULTS: Seven (22.6%), 5 (16.1%), and 6 (19.4%) of clinical diagnosis was changed after TBLC for Pulmonologist A, for Pulmonologist B, and for consensus, respectively. The treatment strategy was changed in 7 (22.6%), 8 (25.9%), and 6 (19.4%) cases after TBLC for Pulmonologist A, for Pulmonologist B and for consensus, respectively. The definite or high confidence level of the consensus treatment strategy was 54.8% (17/31) without TBLC and 83.9% (26/31) with TBLC. There were 6 cases of moderate bleeding, but no other complications were noted. CONCLUSIONS: Pathological information from TBLC may contribute to decision-making in treatment strategies for the progression of DPLD, and it may be safely performed.

Radiographic features and poor prognostic factors of interstitial lung disease with nivolumab for non-small cell lung cancer.

Nivolumab can cause interstitial lung disease (ILD), which may be fatal; however, mortality risk factors have not been identified. This postmarketing study evaluated the poor prognostic factors of ILD in nivolumab-treated patients with non-small cell lung cancer (NSCLC) in Japan. Clinical and chest imaging findings for each ILD case were assessed by an expert central review committee, and prognosis was evaluated by radiographic findings, including the presence/absence of peritumoral ground-glass opacity (peritumoral-GGO). Poor prognostic factors were identified by univariate and multivariate Cox regression analysis. Of the 238 patients with nivolumab-induced ILD, 37 died. The main radiographic patterns of ILD were cryptogenic organizing pneumonia/chronic eosinophilic pneumonia-like (53.4%), faint infiltration pattern/acute hypersensitivity pneumonia-like (20.2%), diffuse alveolar damage (DAD)-like (10.9%), and nonspecific interstitial pneumonia-like (6.3%). The main poor prognostic factors identified were DAD-like pattern (highest hazard ratio: 10.72), ≤60 days from the start of nivolumab treatment to the onset of ILD, pleural effusion before treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal change in C-reactive protein (CRP) levels. Of the 37 deaths due to ILD, 17 had DAD-like radiographic pattern, three had peritumoral-GGO, and five had a change in radiographic pattern from non-DAD at the onset to DAD-like. Patients with NSCLC who develop ILD during nivolumab treatment should be managed carefully if they have poor prognostic factors such as DAD-like radiographic pattern, onset of ILD ≤60 days from nivolumab initiation, pleural effusion before nivolumab treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal changes in CRP levels.

Treatment and relapse of interstitial lung disease in nivolumab-treated patients with non-small cell lung cancer.

Nivolumab, a human monoclonal antibody against programmed death-1, is approved for the treatment of non-small cell lung cancer (NSCLC). Although nivolumab is generally well tolerated, it can cause interstitial lung disease (ILD), a rare but potentially fatal immune-related adverse event. Currently, there are limited data available on the treatment of nivolumab-induced ILD and its outcome. This retrospective cohort study based on a post-marketing study described the treatment of nivolumab-induced ILD and its outcome in NSCLC patients in Japan through the assessment of clinical and chest imaging findings by an expert central review committee. Treatment details for patients who experienced a relapse of ILD were also analyzed. Of the 238 patients identified as having nivolumab-induced ILD, 37 patients died of ILD. Corticosteroids were used in 207 (87.0%) patients. Of those, 172 (83.1%) patients responded well and survived and 35 (16.9%) died (most died during corticosteroid treatment). A total of nine patients experienced a relapse; at the time of relapse, four patients were taking nivolumab. Of those who were receiving corticosteroids at the time of relapse, three of four patients were taking low doses or had nearly completed dose tapering. All patients (except one, whose treatment was unknown) received corticosteroids for the treatment of relapse, but one patient died. Patients with NSCLC who experience nivolumab-induced ILD are treated effectively with corticosteroids, and providing extra care when ceasing or reducing the corticosteroid dose may prevent relapse of ILD.

Radiological pleuroparenchymal fibroelastosis-like lesion in idiopathic interstitial pneumonias.

BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) is characterised by predominant upper lobe pleural and subpleural lung parenchymal fibrosis. Radiological PPFE-like lesion has been associated with various types of interstitial lung diseases. However, the prevalence and clinical significance of radiological PPFE-like lesion in patients with idiopathic interstitial pneumonias (IIPs) are not fully understood. We aimed to determine the prevalence and clinical impact on survival of radiological PPFE-like lesion in patients with IIPs. METHODS: A post-hoc analysis was conducted using data from the Japanese nationwide cloud-based database of patients with IIPs. All the patients in the database were diagnosed as having IIPs by multidisciplinary discussion. Patients diagnosed with idiopathic PPFE were excluded. Clinical data and chest computed tomography (CT) image of 419 patients with IIPs were analysed. The presence of radiological PPFE-like lesion was independently evaluated by two chest radiologists blind to the clinical data. RESULTS: Of the 419 patients with IIPs, radiological PPFE-like lesions were detected in 101 (24.1%) patients, mainly in idiopathic pulmonary fibrosis (IPF) and unclassifiable IIPs, but less in idiopathic nonspecific interstitial pneumonia. Prognostic analyses revealed that radiological PPFE-like lesion was significantly associated with poor outcome in patients with IIPs, which was independent of age, IPF diagnosis and %FVC. In survival analyses, the patients with radiological PPFE-like lesions had poor survival compared with those without (log-rank, p < 0.0001). Subgroup analyses demonstrated that radiological PPFE-like lesion was significantly associated with poor survival both in patients with IPF and those with unclassifiable IIPs. CONCLUSION: Radiological PPFE-like lesion is a condition that could exist in IIPs, mainly in IPF and unclassifiable IIPs. Importantly, the radiological PPFE-like lesion is a non-invasive marker to predict poor outcome in patients with IIPs, which should be carefully considered in clinical practice.

Cardiovascular magnetic resonance assessment of coronary flow reserve improves risk stratification in heart failure with preserved ejection fraction.

BACKGROUND: Coronary microvascular dysfunction (CMD) has been proposed as a novel mechanism for the pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). Recent studies have suggested the potential utility of coronary flow reserve (CFR) as a marker of CMD in patients with HFpEF. Phase contrast (PC) cine cardiovascular magnetic resonance (CMR) of the coronary sinus has emerged as a non-invasive method to quantify CFR. We aimed to investigate the prognostic value of CMR-derived CFR in patients with HFpEF. METHODS: Data from 163 HFpEF patients (73 ± 9 years; 86 [53%] female) were retrospectively analyzed. Coronary sinus blood flow was measured in all patients, and myocardial blood flow was calculated as coronary sinus blood flow divided by left ventricular mass. CFR was calculated as the myocardial blood flow during adenosine triphosphate infusion divided by that at rest. Adverse events were defined as all-cause death and hospitalization due to HF exacerbation. Event-free survival stratified according to CFR < 2.0 was estimated with Kaplan-Meier survival methods and Log-rank test. RESULTS: During a median follow-up of 4.1 years, 26 patients (16%) experienced adverse events. CMR-derived CFR was significantly lower in HFpEF with adverse events compared with those without (1.93 ± 0.38 vs. 2.67 ± 0.52, p < 0.001). On a Kaplan Meier curve, the rates of adverse events were significantly higher in HFpEF patients with CFR < 2.0 compared with HFpEF with CFR ≥ 2.0 (p < 0.001). The area under the curve of CFR for predicting adverse events was significantly higher than that of LGE (0.881 vs. 0.768, p = 0.037) and GLS (0.881 vs. 0.747, p = 0.036). CONCLUSIONS: CFR assessed using coronary sinus PC cine CMR may be useful as a non-invasive prognostic marker for HFpEF patients.

Prognostic value of resting coronary sinus flow determined by phase-contrast cine cardiovascular magnetic resonance in patients with known or suspected coronary artery disease.

BACKGROUND: Phase-contrast cine cardiovascular magnetic resonance (CMR) of the coronary sinus has emerged as a non-invasive method to measure coronary sinus blood flow (CSBF) and coronary flow reserve (CFR). We aimed to compare the prognostic value of resting CSBF and CFR for predicting major adverse cardiac events (MACE) in patients with known or suspected coronary artery disease (CAD) who underwent vasodilator stress CMR. METHODS: We studied 693 patients with known CAD and 519 patients with suspected CAD admitted to our hospital between 2009 and 2019. The CFR was calculated as the CSBF during adenosine triphosphate infusion divided by CSBF at rest. MACE was defined as composite of cardiovascular death, acute coronary syndrome, heart failure hospitalization, and sustained ventricular tachyarrhythmia. RESULTS: During a median follow-up of 4.6 years, 92 patients (8%) experienced MACE. The resting CSBF was significantly higher in patients with MACE than in patients without MACE (114.7 ± 44.9 mL/min vs. 84.7 ± 30.9 mL/min, p < 0.001 for known CAD; 122.2 ± 33.3 mL/min vs. 86.6 ± 36.7 mL/min, p < 0.001 for suspected CAD). The resting CSBF remained a significant predictor for MACE after adjusting clinical and CMR variables (hazard ratio [HR] of resting CSBF higher than the median: 3.18, p = 0.0083 for known CAD; HR: 23.3, p < 0.001 for suspected CAD). The area under the curve for predicting MACE was 0.73 for resting CSBF, 0.72 for CFR (p = 0.78) in patients with known CAD, and 0.82 for resting CSBF, 0.83 (p = 0.58) for CFR in patients with suspected CAD. CONCLUSIONS: The resting CSBF may be a useful non-invasive method for the risk stratification of patients with known or suspected CAD without any radiation exposure, contrast media, or pharmacological vasodilator agents.

Impaired coronary flow reserve evaluated by phase-contrast cine magnetic resonance imaging in patients with atrial fibrillations.

Myocardial perfusion and perfusion reserve are diminished in patients with atrial fibrillation (AF). Phase-contrast (PC) cine magnetic resonance imaging (MRI) of the coronary sinus serves as a non-invasive means of quantifying coronary flow reserve (CFR) without any radioactive tracer. The present study aimed to evaluate the utility of PC cine MRI of the coronary sinus for assessing decreased CFR in patients with AF. We studied 362 patients with known or suspected coronary artery disease (CAD) [age 72 ± 9 years; 267 (74%) male; 90 (25%) had AF] and 20 age- and gender-matched control subjects [age 72 ± 9 years, 14 (70%) male]. Using a 1.5-T MR scanner and cardiac coils, blood flow of the coronary sinus (CBF) was quantified by PC cine MRI. CFR was calculated as CBF during adenosine triphosphate infusion divided by CBF at rest. CFR was significantly lower in patients with AF than in those without AF among all patients (n = 362) (2.45 ± 0.42 vs. 2.71 ± 0.58, p < 0.001), in patients with known CAD (n = 155) (2.40 ± 0.46 vs. 2.72 ± 0.58, p = 0.002), and in those with suspected CAD (n = 207) (2.49 ± 0.40 vs. 2.72 ± 0.59, p = 0.007). Significant differences in CFR were found between controls and patients without AF (3.12 ± 0.52 vs. 2.71 ± 0.58, p < 0.001). AF was independently associated with CFR in both known CAD patients [ß = - 0.248, 95% confidence interval (CI): - 0.561 to - 0.119, p = 0.003) and suspected CAD patients (ß = - 0.154, 95% CI - 0.353 to - 0.034, p = 0.018). The presence of AF was related to impaired CFR in both known and suspected CAD patients. PC cine MRI of the coronary sinus can be useful for detecting impaired CFR in patients with AF.

Coronary artery disease and heart failure in patients with idiopathic pulmonary fibrosis.

The aim of this study was to investigate the prevalence and prognostic value of coronary artery disease (CAD) and heart failure (HF) in patients with idiopathic pulmonary fibrosis (IPF). Thirteen hundred and fifty-eight patients with interstitial lung disease [851 (62%) males, mean age: 68 ± 10 years] were retrospectively analyzed. CAD was defined as (1) the presence of a clinical diagnosis of angina pectoris, (2) clinical diagnosis of a myocardial infarction, and (3) coronary angiography showing ≥ 1 vessel with a stenosis of > 75%. The definition of HF was made according to the modified Framingham criteria. Compared to the non-IPF group (n = 790), the IPF group (n = 568) had a significantly higher prevalence of CAD (9.3% vs. 4.4%, p < 0.001) and HF (8.2% vs. 3.7%, p < 0.001). During a median follow-up of 1.6 years, 152 deaths were identified. The patients with HF had a significantly worse prognosis than those without HF both in the non-IPF group and IPF group (both p < 0.05). However, the prognosis did not significantly differ between the patients with CAD and those without CAD both in the non-IPF group and IPF group. The presence of HF was an independent predictor of death in the IPF [hazard ratio (HR) 3.67, 95% confidence interval (CI) 1.57-8.56, p = 0.0025] and non-IPF (HR 5.07, 95% CI 1.44-17.86, p = 0.011) patients. The prevalence of CAD and HF was significantly higher in IPF than non-IPF patients. In addition, the presence of HF was a significant prognostic factor for both IPF and non-IPF patients. These results indicated that the importance of HF as a comorbidity for patients with ILD.

Inhalation challenge test using pigeon eggs for chronic hypersensitivity pneumonitis.

BACKGROUND: Chronic hypersensitivity pneumonitis (CHP) remains a diagnostic challenge. The process of collecting and extracting serum and droppings from causative animals for the inhalation challenge test is complicated and the risk of inducing disease progression exists. OBJECTIVE: To investigate the utility and safety of an inhalation challenge test using pigeon eggs. METHODS: Pigeon eggs were pasteurized and mixed with a saline solution to produce an inhalation fluid. An inhalation challenge test was conducted on 19 patients with bird-related CHP and 17 patients with interstitial lung disease other than bird-related CHP. To identify antigens in pigeon eggs, the antigen-antibody responses of the pigeon eggs and serum from patients were evaluated using Western blotting. RESULTS: The mean changes in C-reactive protein, alveolar-arterial oxygen difference, erythrocyte sedimentation rate, and lactate dehydrogenase significantly increased by 0.32 mg/dL (P = .014), 7.8 Torr (P = .002), 1.4 mm/h (P = .012), and 5.4 U/mL (P = .0019), respectively, in bird-related CHP group compared to the control 24 hours after the inhalation challenge test. Furthermore, within 24 hours of the inhalation test, the mean forced vital capacity decreased by 2.3% in the bird-related CHP group compared with a decline of 0.05% in the control group (P = .035). Serum collected from seven bird-related CHP patients who underwent the inhalation challenge test and reacted to antigens with molecular weights of 37-75 KDa, and these molecular weights were consistent with egg albumin and globulin. CONCLUSION: Since a mild response was observed after the inhalation challenge test using pigeon eggs, this test was an obvious candidate for diagnosing bird-related CHP.