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Systemic corticosteroid administration, also called short bursts (SB), is harmful for patients with asthma; however, the actual burden of one-day SB remains unsolved. This study aimed to elucidate the characteristics of patients requiring one-day SB against asthma in clinical practice. Consecutive patients who regularly visited our hospital for asthma treatment between January 2019 and December 2020 were reviewed and followed for one year. SB was defined as ≥3 days of systemic corticosteroid treatment for an exacerbation. One-day SB was defined as one-day of systemic corticosteroid to treat an exacerbation. The one-day SB group included patients who received only one-day SB but no SB during the preceding year. Frequent SB was defined as that occurring ≥2 times/year. Data on 229 patients were analyzed. Among them, 2.6% (95% confidence interval 1.2–5.6%) were in the one-day SB group. The one-day SB group was female-dominant, obese, non-eosinophilic, and non-atopic. The median one-day SB was 1.5 times/year and almost half of one-day SB were performed by patients themselves. Independent of the low pulmonary function, high blood eosinophil count, and inhaled corticosteroid dose, one-day SB was associated with future frequent SB (adjusted odds ratio = 18.2, 95% confidence interval 1.1–288, P = 0.040, compared to the no SB group). Although one-day SB was not frequently experienced, even one-day SB without conventional SB was associated with future frequent SB. It is important to grasp the actual condition of one-day SB and to reinforce the treatment used. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) for malignant lesions are associated with immune‐related adverse events (irAEs), but reports about severe eosinophilia induced by ICIs are scarce. A 73‐year‐old man with lung squamous cell carcinoma was treated by chemotherapy (carboplatin plus paclitaxel) and ICIs (nivolumab plus ipilimumab). After two cycles of chemotherapy, the ICIs were continued. After 5 months, the eosinophilia, which had exceeded 5000/μl, increasingly deteriorated, and the only detected irAE was a grade 1 rash. Under continuation of the ICIs, although the eosinophilia decreased, a grade 3 rash and severe pruritis subsequently appeared. Squamous cell carcinoma antigen (SCCA) was steeply increased simultaneously. A complete response had been achieved, and oral prednisolone markedly improved the rash, pruritis, and eosinophilia. Clinicians should be aware that precedent severe eosinophilia and subsequent severe irAE could occur in patients treated by nivolumab and ipilimumab, and SCCA elevation could be associated with dermatologic irAE. [ABSTRACT FROM AUTHOR]

The data on intermittent systemic corticosteroid therapy for asthma exacerbation, clinically called a "short burst," is limited. This study aimed to investigate the characteristics of patients with frequent systemic corticosteroid bursts for asthma in real clinical practice. Consecutive patients who regularly visited our hospital for asthma treatment between January 2019 and December 2020 were reviewed. The number of systemic corticosteroid bursts during the past 1 year was collected, and those with frequent bursts (≥2 times/year) were defined as the Frequent group. Data on 236 patients were analyzed. Among them, 5.5% (95% confidence interval 3.2–9.2%) were in the Frequent group. In the Frequent group, 23% of patients had no unplanned visits, and 38% experienced at least one corticosteroid burst without visiting a physician (self-medication). One-third of patients did not undertake high-dose inhaled corticosteroid treatment, and three-fourths of patients did not undertake long-acting muscarinic antagonist treatment. Low pulmonary function and increased blood eosinophils were independently associated with the Frequent group (adjusted odds ratio = 0.73, 95% confidence interval 0.55–0.99, P = 0.039, per 10% predicted increase in a forced expiratory volume in 1 s; adjusted odds ratio = 1.15, 95% confidence interval 1.02–1.29, P = 0.025, per 100/μL increase in blood eosinophils). There was a certain rate of frequent corticosteroid bursts in real clinical practice. It is important to determine the actual condition, as some patients experienced "hidden" frequent bursts and have the option to reinforce the treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Although impaired health-related quality of life (HRQOL) has been reported in patients with sarcoidosis, there is currently no sarcoidosis-specific questionnaire in Japan. The 29-item Sarcoidosis Health Questionnaire (SHQ), originally developed in the United States, is the only sarcoidosis-specific HRQOL questionnaire currently available. The primary aim of this study was to develop and validate a Japanese version of the SHQ. Findings The SHQ was translated into Japanese following the forward-backward procedure. The reliability and validity of the Japanese version of the SHQ were examined. One hundred twenty-two Japanese patients with biopsy-proven sarcoidosis were evaluated by the SHQ, the Medical Outcomes Study 36-item short form (SF-36), the St. George's Respiratory Questionnaire (SGRQ), chest radiography, an electrocardiogram, laboratory blood tests, pulmonary function tests, an echocardiogram, and assessments of dyspnea and depressive symptoms. The SHQ was found to have acceptable levels of internal consistency (Cronbach's coefficient α values = 0.68 to 0.91). SHQ scores correlated significantly with scores on the SF-36 and SGRQ. The domain or total scores on the SHQ also significantly correlated with serum levels of the soluble interleukin-2 receptor, the percentage of the predicted forced vital capacity, pulmonary arterial systolic pressure, dyspnea, and depressive symptoms. Also, the SHQ scores of patients who had one or two organ systems affected by sarcoidosis were significantly different from those of patients who had three or more organ systems involvement. Conclusions The Japanese version of the SHQ can be used to assess the HRQOL of patients with sarcoidosis.

Background: The prevalence of chronic kidney disease (CKD) increases with age as with idiopathic pulmonary fibrosis (IPF). Objectives: We assessed the prevalence of CKD (stages 3-5) and investigated the relationship of CKD to clinical features and outcomes in patients with IPF. Methods: This study comprised 123 patients with IPF; 61 subjects with chronic obstructive pulmonary disease (COPD), which was reportedly associated with CKD, were also enrolled as a disease control. CKD (stages 3-5) was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². Results: Thirty-seven patients (30%) with IPF and 14 controls (23%) with COPD were diagnosed with CKD, and these frequencies were not significantly different. The patients with IPF and CKD were older (p < 0.01) and had a higher frequency of hypertension (p = 0.048) and ischemic heart disease (p = 0.02) than those with IPF but without CKD. Furthermore, the diffusing capacity of the lung for carbon monoxide (DLCO) and the 6-min walking distance in the patients with CKD were significantly lower (40.0 ± 13.2 vs. 45.9 ± 14.4%, p = 0.04, and 416 ± 129 vs. 474 ± 84 m, p = 0.01, respectively) than in the patients without CKD. The outcome of the patients with CKD showed significantly worse survival compared with the patients without CKD (p = 0.04). Moreover, eGFR remained an independent predictor of survival after adjusting for age and pulmonary function data. Conclusion: A substantial percentage of IPF patients have CKD. CKD with a low eGFR was associated with decreased survival in IPF. [ABSTRACT FROM AUTHOR]

Background: Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown etiology with few current treatment options. Recently, we determined an important role of prostaglandin F2α (PGF2α) in pulmonary fibrosis by using a bleomycin-induced pulmonary fibrosis model and found an abundance of PGF2α in bronchoalveolar lavage fluid of IPF patients. We investigated the role of PGF2α in human IPF by assessing plasma concentrations of 15-keto-dihydro PGF2α, a stable metabolite of PGF2α. Methods: We measured plasma concentrations of 15-keto-dihydro PGF2α in 91 IPF patients and compared these values with those of controls (n = 25). We further investigated the relationships of plasma 15-keto-dihydro PGF2α concentrations with disease severity and mortality. Results: Plasma concentrations of 15-keto-dihydro PGF2α were significantly higher in IPF patients than controls (p<0.001). Plasma concentrations of this metabolite were significantly correlated with forced expiratory volume in 1 second (Rs [correlation coefficient] = −0.34, p = 0.004), forced vital capacity (Rs = −0.33, p = 0.005), diffusing capacity for carbon monoxide (Rs = −0.36, p = 0.003), the composite physiologic index (Rs = 0.40, p = 0.001), 6-minute walk distance (Rs = −0.24, p = 0.04) and end-exercise oxygen saturation (Rs = −0.25, p = 0.04) when patients with emphysema were excluded. Multivariate analysis using stepwise Cox proportional hazards model showed that a higher composite physiologic index (relative risk = 1.049, p = 0.002) and plasma 15-keto-dihydro PGF2α concentrations (relative risk = 1.005, p = 0.002) were independently associated with an increased risk of mortality. Conclusions: We demonstrated significant associations of plasma concentrations of PGF2α metabolites with disease severity and prognosis, which support a potential pathogenic role for PGF2α in human IPF. [ABSTRACT FROM AUTHOR]

Background: Both obstructive sleep apnea (OSA) and a novel lipocalin, neutrophil gelatinase associated lipocalin (Ngal), have been reported to be closely linked with cardiovascular disease and loss of kidney function through chronic inflammation. However, the relationship between OSA and Ngal has never been investigated. Objectives: To evaluate the relationship between Ngal and OSA in clinical practice. Methods: In 102 patients, polysomnography was performed to diagnose OSA and plasma Ngal levels were measured. The correlations between Ngal levels and OSA severity and other clinical variables were evaluated. Of the 46 patients who began treatment with continuous positive airway pressure (CPAP), Ngal levels were reevaluated after three months of treatment in 25 patients. Results: The Ngal level correlated significantly with OSA severity as determined by the apnea hypopnea index (r = 0.24, p = 0.01) and 4% oxygen desaturation index (ODI) (r = 0.26, p = 0.01). Multiple regression analysis showed that the Ngal level was associated with 4%ODI independently of other clinical variables. Compliance was good in 13 of the 25 patients who used CPAP. Although the OSA (4%ODI: 33.1±16.7 to 1.1±1.9/h, p<0.01) had significantly improved in those with good compliance, the Ngal levels were not significantly changed (60.5±18. 1 before CPAP vs 64.2±13.9 ng/ml after CPAP, p = 0.27). Conclusions: Plasma Ngal levels were positively associated with the severity of OSA. However, the contribution rate of OSA to systemic Ngal secretion was small and changes in Ngal levels appeared to be influenced largely by other confounding factors. Therefore, it does not seem reasonable to use the Ngal level as a specific biomarker of OSA in clinical practice. [ABSTRACT FROM AUTHOR]

Objective. The availability of many types of inhalers in the treatment of asthma has resulted in a wide range of prescription choices for clinicians. With so many devices available, however, there is some confusion regarding their proper use among both medical staff and patients. Since 2007, Kitano Hospital and Kita-ku Pharmaceutical Association, Osaka, Japan, have provided a network system for delivering instruction on correct inhalation technique through community pharmacists. We examined the clinical effects of this network system. Methods. Our measurements included the manner in which community pharmacists instruct patients with asthma, the frequency of asthma exacerbations, patients' adherence to inhalation therapy using a 5-point Likert scale questionnaire, and patients' health status both prior to this system and at 4 years after. Results. Usable information was obtained from 53 community pharmacists and 146 patients with asthma at baseline and from 60 community pharmacists and 148 patients at 4 years. When compared with baseline values, significant improvement was found in pharmacists' instruction and significant decreases were observed in the frequency of asthma exacerbations (1.4 ± 1.6 vs. 1.0 ± 1.4 times/yr, p = .042) and emergency room visits (0.5 ± 1.0 vs. 0.2 ± 0.5 times/yr, p = .004). Adherence to the inhalation regimen significantly increased (4.0 ± 0.7 vs. 4.2 ± 0.8, p = .041), but health status was unchanged. Conclusions. Our network system may improve asthma control and adherence to inhalation regimens. [ABSTRACT FROM AUTHOR]

Summary: Background: Anti-CADM-140 antibody (anti-CADM-140), also referred to as anti-melanoma differentiation-associated gene 5 (MDA5) antibody, is a myositis-specific antibody identified in the sera of patients with clinically amyopathic dermatomyositis (C-ADM) and is associated with a worse prognosis in dermatomyositis-associated interstitial lung disease (DM-ILD). We sought to determine high-resolution computed tomography (HRCT) features of DM-ILD with anti-CADM-140. Methods: Twenty-five patients newly diagnosed with DM-ILD at Kyoto University Hospital between 2005 and 2009 were retrospectively reviewed. Serum anti-CADM-140 was measured in all patients at their first visit. Chest HRCT images taken prior to treatment were classified based on the dominant findings and their distribution, and compared between patients with and without the antibody. Results: Of 25 DM-ILD patients, 12 were positive and 13 were negative for anti-CADM-140. HRCT patterns differed significantly between anti-CADM-140-positive and negative patients (P = 0.002). Lower consolidation or ground-glass attenuation (GGA) pattern (50.0%) and random GGA pattern (33.3%) were the predominant patterns in anti-CADM-140-positive cases, while lower reticulation pattern (69.2%) was frequently seen in anti-CADM-140-negative cases. Anti-CADM-140-positive cases were also significantly characterized by the absence of intralobular reticular opacities (0% in anti-CADM-140 (+) vs. 84.6% in anti-CADM-140 (−), P < 0.0001). Conclusions: Anti-CADM-140-positive DM-ILD was characterized by lower consolidation or GGA pattern, random GGA pattern, and the absence of intralobular reticular opacities. [Copyright &y& Elsevier]

Summary: Objectives: Antisynthetase syndrome (ASS) is characterized by autoantibodies to aminoacyl-tRNA synthetases (anti-synthetase) and it is frequently associated with interstitial lung disease. The purpose of this study was to elucidate the prevalence and characteristics of the anti-synthetase positive subpopulation among idiopathic interstitial pneumonias (IIPs) and to clarify the importance of screening for these antibodies. Methods: A retrospective study was performed in 198 consecutive cases with IIPs. Screening for six anti-synthetase antibodies was performed in all cases. Clinical profiles of all cases were compared with reference to the presence of anti-synthetase. High-resolution computed tomography (HRCT) findings of anti-synthetase positive cases were also analyzed. Results: 13 cases (6.6%) were positive for anti-synthetase. Anti-EJ was most prevalent, followed by anti-PL-12. Onset ages of anti-synthetase positive cases were younger than those of anti-synthetase negative cases. Extrapulmonary features of ASS were absent in 6 anti-synthetase positive cases (46.2%). Histologically, among 5 UIP with lymphoid follicles and 11 NSIP cases, the prevalence of anti-synthetase positive cases was 8/16 (50%). On HRCT, ground glass opacity and traction bronchiectasis were the major findings in anti-synthetase positive cases, while honeycombing was absent. Conclusions: Anti-synthetase positive cases were not rare among IIPs. Anti-synthetase should be screened for in IIPs, especially in pathological NSIP or UIP with lymphoid follicles. These patients should be screened for anti-synthetase even if no suggestive extrapulmonary manifestation exists. [ABSTRACT FROM AUTHOR]

Summary: Background: Obstructive sleep apnea (OSA) has both systemic and local effects partly through the increased oxidative stress caused by intermittent hypoxia and reoxygenation. However, lung-specific biomarkers in OSA have not been fully assessed in comparison with systemic biomarkers such as C-reactive protein (CRP), although results of a recent study having a small sample size indicated KL-6 as one candidate. Methods: Subjects of the present study were 197 patients suspected to have OSA. In addition to polysomnography, we also measured serum levels of KL-6, surfactant protein-D (SP-D) and CRP and pulmonary function. We examined the relationships of different biomarkers with OSA severity and pulmonary function. Results: The apnea/hypopnea index (AHI) was significantly positively correlated with serum KL-6 levels even after adjustment for body mass index (BMI) and smoking (p = 0.03), but not with SP-D and CRP. Also, a significant trend for an increase in serum KL-6 was noted in accordance with the severity of OSA even after adjustment for BMI and smoking (β coefficient = 0.18, p = 0.02). Additionally, elevated KL-6 levels were significantly associated with restrictive lung function disturbance and gas exchange derangement after adjustment for obesity and smoking, which contrasted with CRP whose elevations were significantly associated with worsened airflow limitation and increased lung volume. Conclusions: Serum KL-6 levels may reflect the degree of subclinical lung injury associated with OSA independently of obesity or smoking, unlike CRP. We consider that KL-6 can be a potential candidate as a lung-specific biomarker of OSA and might provide complementary information on systemic biomarkers in assessing OSA. [Copyright &y& Elsevier]

Background: Although impaired health-related quality of life (HRQOL) has been reported in patients with sarcoidosis, there is currently no sarcoidosis-specific questionnaire in Japan. The 29-item Sarcoidosis Health Questionnaire (SHQ), originally developed in the United States, is the only sarcoidosis-specific HRQOL questionnaire currently available. The primary aim of this study was to develop and validate a Japanese version of the SHQ. Findings: The SHQ was translated into Japanese following the forward-backward procedure. The reliability and validity of the Japanese version of the SHQ were examined. One hundred twenty-two Japanese patients with biopsy-proven sarcoidosis were evaluated by the SHQ, the Medical Outcomes Study 36-item short form (SF-36), the St. George's Respiratory Questionnaire (SGRQ), chest radiography, an electrocardiogram, laboratory blood tests, pulmonary function tests, an echocardiogram, and assessments of dyspnea and depressive symptoms. The SHQ was found to have acceptable levels of internal consistency (Cronbach's coefficient α values = 0.68 to 0.91). SHQ scores correlated significantly with scores on the SF-36 and SGRQ. The domain or total scores on the SHQ also significantly correlated with serum levels of the soluble interleukin-2 receptor, the percentage of the predicted forced vital capacity, pulmonary arterial systolic pressure, dyspnea, and depressive symptoms. Also, the SHQ scores of patients who had one or two organ systems affected by sarcoidosis were significantly different from those of patients who had three or more organ systems involvement. Conclusions: The Japanese version of the SHQ can be used to assess the HRQOL of patients with sarcoidosis. [ABSTRACT FROM AUTHOR]

Background: Adherence to inhalation therapy is a critical determinant of the success of asthma management. Reasons for nonadherence have been well studied, but reasons for good adherence are poorly understood. Understanding the mechanisms of adherence to inhalation therapy is important in developing strategies to promote adherence. The objective of this study was to assess the factors and mechanisms that contribute to and the clinical outcomes relating to adherence to inhalation therapy. Methods: The factors and outcomes related to adherence to inhalation therapy were examined cross-sectionally in 176 adults with asthma using a self-reported adherence questionnaire that consisted of four items dealing with the use of inhaled controller medications. A 5-point Likert scale was used for the responses to each item. Adherence was assessed based on the overall mean adherence score. Results: Of the 176 patients who were potential participants, 146 (83%) responded with usable information. Significant factors associated with the overall mean adherence score were older age ( r = .18, p = .032) and receiving repeated instruction on inhalation techniques ( p = .0016). Of the 146 respondents, 25 (17.1%) patients were given repeated verbal instruction or demonstrations of inhalation technique by a respiratory physician. On logistic regression analysis, good adherence to inhalation therapy was significantly related to the receiving of repeated instruction on inhalation technique, with an odds ratio of 2.90 (95% confidence interval 1.07–7.88; p = .037). Furthermore, less intentional nonadherent behavior was reported in patients with repeated instruction on inhalation technique compared to those without it. A significant correlation was found between the overall mean adherence score and the frequency of asthma exacerbations ( r = −.19, p = .021), emergency room visits ( r = −.19, p = .042), and the health-related quality of life score (St. George's Respiratory Questionnaire: Total, r = −.22, p = .024; Symptoms, r = −.21, p = .022; Impacts, r = −.20, p = .035). Conclusions: Repeated instruction on inhalation techniques may contribute to adherence to inhalation therapy through decreasing intentional nonadherence. Furthermore, good adherence to the therapeutic regimen may offer good asthma-related outcomes. [ABSTRACT FROM AUTHOR]

After the talc pleurodesis, CT showed the tract made from the chest tube even after its removal. The unexpanded thoracic space might also contribute to it; thus, gathering specific medical history is important to understand this rare phenomenon. [ABSTRACT FROM AUTHOR]

Omalizumab can cause hypersensitivity reactions. We herein report the first case of an 18-year-old woman with refractory cough-predominant asthma that correlated with allergic reactions caused by omalizumab and the coronavirus disease 2019 (COVID-19) vaccine. The patient developed angioedema after taking omalizumab. She had previously experienced intense coughing immediately after receiving a COVID-19 vaccine. A skin prick test was positive for polysorbate 20, which was probably the cause of the allergic reactions to omalizumab and the COVID-19 vaccine. Clinicians should check for an allergic reaction, irrespective of its intensity, triggered by polysorbate and be careful when prescribing biologics to patients in order to avoid allergic reactions.

Ethambutol-induced optic neuropathy (EON) is a well-known complication, although low-dose ethambutol seldom causes EON. An 85-year-old man with non-tuberculous mycobacterial lung disease was taking antibiotics, including low-dose ethambutol. On day 85 of treatment, the diagnosis of EON was made. Despite prior discontinuation, his best corrected visual acuity drastically deteriorated from 20/17 (right eye) and 20/20 (left eye) to 20/330 (right eye) and 20/1,000 (left eye) within 3 weeks, and this symptom did not resolve. To our knowledge, there have been no reported cases with drastically progressing and irreversible EON even after the withdrawal of low-dose and short-term ethambutol.

Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) results in poor survival. The objective of the present study was to elucidate the impact of asymmetrical ground-glass opacity (GGO) and/or consolidation on outcomes in patients with AE-IPF. The cases of 59 consecutive patients with AE-IPF were retrospectively reviewed. High-resolution computed tomography (HRCT) at diagnosis of an AE was assessed to determine the disease extent and asymmetry. Asymmetrical AE was defined as a right-to-left ratio of GGO and consolidation ≥2.0 or ≤0.5. The impacts of HRCT indices and other clinical parameters on 180-day mortality were analysed. The overall 180-day mortality rate was 59.2%, and asymmetrical AE was observed in 13 patients (22.0%). A multivariate analysis revealed that asymmetrical AE was a significant predictor of 180-day mortality (hazard ratio=0.36, p=0.047), long-term oxygen therapy before AE and serum lactate dehydrogenase levels. The 180-day mortality of patients with asymmetrical AE was significantly lower than that of patients with symmetrical AE (asymmetrical AE 30.8% versus symmetrical AE 68.2%, p=0.03). An asymmetrical distribution of GGO and/or consolidation is a predictor of survival in patients with AE-IPF., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at openres.ersjournals.com

IOS can predict airway hyperresponsiveness and long-term outcome in patients with pulmonary sarcoidosis http://ow.ly/bkQH307VD4m., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erjor.ersjournals.com

Background: Recent epidemiological studies have shown that patients with interstitial pneumonia have an increased risk of cardiovascular events. Although the presence of a coagulation/fibrinolysis abnormality in idiopathic pulmonary fibrosis (IPF) has been reported, platelet aggregability has not been evaluated in interstitial pneumonias. This study aimed to investigate platelet aggregability in patients with interstitial pneumonias., Methods: This observational cohort study included 59 patients with interstitial pneumonias [19 with IPF, 23 with other idiopathic interstitial pneumonias (IIPs), and 17 with connective tissue disease-associated interstitial pneumonias (CTD-IPs)] and 23 healthy control subjects. ADP- and collagen-induced platelet aggregability was measured together with coagulation/fibrinolysis markers. Whole blood (WB) and platelet rich plasma platelet aggregation were measured using the screen filtration pressure and optical aggregometer techniques, respectively. The platelet aggregation threshold index (PATI) was calculated; a lower PATI indicated enhanced platelet aggregability., Results: ADP-induced WB-PATI was significantly decreased in CTD-IPs [log WB-PATI median 0.31 (inter-quartile range, 0.07-0.34) μM, n = 17] compared with that in controls [0.35 (0.32-0.45) μM, n = 23] (p < 0.05). However, there was no significant difference in platelet aggregability between the other patient groups and controls. In contrast, d-dimer, thrombin-antithrombin complex, and von Willebrand factor levels were significantly higher in all patient groups compared with those in controls (p < 0.001). Platelet aggregability was not associated with either disease severity or survival., Conclusions: Serum coagulation and fibrinolysis markers significantly increased in IIPs and CTD-IPs. In contrast, platelet aggregability was only weakly enhanced in CTDs, but not in IIPs.

Background: Quantitative computed tomography (CT) analysis has been proposed as a means of objectively assessing fibrotic interstitial pneumonia (IP) including idiopathic pulmonary fibrosis (IPF). We investigated whether percentages of high-attenuation areas (HAA%) and cystic areas (CA%) quantified from CT images were useful as indices of fibrotic IP., Methods: CT images of 74 patients with fibrotic idiopathic interstitial pneumonias (IPF, 36; non-specific interstitial pneumonia, 9; unclassifiable idiopathic interstitial pneumonia, 29) were analyzed via in-house computer software, which automatically calculated HAA%, CA%, mean lung density (MLD), standard deviation of lung density (SD-LD), kurtosis, and skewness from CT attenuation histograms. These indices were compared in each instance with physiologic measures, visual fibrosis score, clinical diagnosis, radiologic CT pattern, and prognosis., Results: HAA% correlated significantly with physiologic measures and visual fibrosis score to a moderate extent (%forced vital capacity, rs = -0.59; % carbon monoxide diffusion capacity, rs = -0.43; fibrosis score, rs = 0.23). Densitometric parameters (MLD, SD-LD, kurtosis, and skewness) correlated significantly with physiologic measures and fibrosis score (|rs| = 0.28-0.59). CA% showed no association with pulmonary functions but differed significantly between IPF and other interstitial pneumonias (IPs) (1.50 ± 2.41% vs. 0.41 ± 0.80%; P < 0.01) and between the definite usual interstitial pneumonia (UIP) pattern and other patterns (1.48 ± 2.38% vs. 0.55 ± 1.19%; P < 0.01). On univariate analysis, HAA%, MLD, SD-LD, kurtosis, skewness, fibrosis score, and definite UIP pattern all correlated with survival, with kurtosis alone identified as a significant predictor of mortality on multivariate analysis (hazard ratio = 0.67; 95% CI, 0.44-0.96; P = 0.03)., Conclusion: CA% and HAA% are novel quantitative CT indices with differing properties in fibrotic IP evaluations. HAA% largely reflects physiologic impairments, whereas CA% corresponds with diagnosis and HRCT pattern. Of the CT indices examined, kurtosis constituted the strongest predictor of mortality.

Background: Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown etiology with few current treatment options. Recently, we determined an important role of prostaglandin F2α (PGF2α) in pulmonary fibrosis by using a bleomycin-induced pulmonary fibrosis model and found an abundance of PGF2α in bronchoalveolar lavage fluid of IPF patients. We investigated the role of PGF2α in human IPF by assessing plasma concentrations of 15-keto-dihydro PGF2α, a stable metabolite of PGF2α., Methods: We measured plasma concentrations of 15-keto-dihydro PGF2α in 91 IPF patients and compared these values with those of controls (n = 25). We further investigated the relationships of plasma 15-keto-dihydro PGF2α concentrations with disease severity and mortality., Results: Plasma concentrations of 15-keto-dihydro PGF2α were significantly higher in IPF patients than controls (p<0.001). Plasma concentrations of this metabolite were significantly correlated with forced expiratory volume in 1 second (Rs [correlation coefficient] = -0.34, p = 0.004), forced vital capacity (Rs = -0.33, p = 0.005), diffusing capacity for carbon monoxide (Rs = -0.36, p = 0.003), the composite physiologic index (Rs = 0.40, p = 0.001), 6-minute walk distance (Rs = -0.24, p = 0.04) and end-exercise oxygen saturation (Rs = -0.25, p = 0.04) when patients with emphysema were excluded. Multivariate analysis using stepwise Cox proportional hazards model showed that a higher composite physiologic index (relative risk = 1.049, p = 0.002) and plasma 15-keto-dihydro PGF2α concentrations (relative risk = 1.005, p = 0.002) were independently associated with an increased risk of mortality., Conclusions: We demonstrated significant associations of plasma concentrations of PGF2α metabolites with disease severity and prognosis, which support a potential pathogenic role for PGF2α in human IPF.

Objective: We identified the prognostic relevance of pneumothorax in interstitial lung disease (ILD) patients and evaluated the efficacy and safety of autologous blood-patch pleurodesis., Methods: We retrospectively reviewed 59 occurrences of pneumothorax in 34 ILD patients identified over a 12-year period., Results: Air leakage ceased in 16 of 22 (72.7%) episodes after blood pleurodesis and in 11 of 14 (78.6%) episodes after chemical pleurodesis. Both the cure ratio and recurrence ratio in the cure episodes were comparable with those in the chemical pleurodesis group (p=0.99 and 0.99, respectively). In addition, there were no harmful events associated with blood pleurodesis. The median survival time after the first episode of pneumothorax was less than 9 months in patients with idiopathic interstitial pneumonia (IIP) and only around 3 years in the patients with other types of ILD, which have essentially favorable outcomes. Kaplan-Meier survival estimates were significantly worse in the patients with concomitant pneumomediastinum than in those without (p<0.05). A multivariate Cox regression analysis identified that the number of episodes of pneumothorax, IIP diagnosis and concomitant pneumomediastinum were independent predictors of death., Conclusion: Autologous blood-patch pleurodesis is safe and worth considering as a first-line treatment for pneumothorax secondary to ILD. However, despite treatments, the prognosis after the onset of pneumothorax in ILD patients was found to be poor. In addition, concomitant pneumomediastinum may further worsen the prognosis.