Tension Pneumomediastinum in Anti-MDA5 Antibody-positive Dermatomyositis-associated Interstitial Lung Disease: A Case Report and Literature Review.

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM)-associated interstitial lung disease (ILD) can sometimes be complicated by pneumomediastinum, although tension pneumomediastinum is extremely rare. We herein report a case of anti-MDA5 antibody-positive DM-ILD that worsened subcutaneous and mediastinal emphysema during treatment. Hypotension and worsening respiratory failure were observed on day 20 of treatment. Mediastinal drainage under video-assisted thoracoscopic surgery promptly improved the patient's circulatory and respiratory status. Tension pneumomediastinum is a rare complication; however, it is a serious condition that may lead to hypotension or cardiac arrest and requires a prompt diagnosis and treatment.

The impact of factor Xa inhibitors on bleeding risk in patients with respiratory diseases.

It is unclear which factor Xa (FXa) inhibitors are associated with higher bleeding risk in patients with respiratory diseases, and there are no studies on the association between prothrombin time-international normalized ratio (PT-INR) and bleeding risk. We conducted a retrospective cohort study comparing 1-year-outcomes and PT-INR between patients with respiratory diseases treated with rivaroxaban (R group, n = 82) or edoxaban (E group, n = 138) for atrial fibrillation or venous thromboembolism from 2013 to 2021. The most frequent event of all bleeding discontinuations was respiratory bleeding in both groups (7.3 and 4.3%, respectively). The cumulative incidence of bleeding discontinuation was significantly higher in the R group (25.6%) than in the E group (14.4%) (hazard ratio [HR], 2.29; 95% confidence interval [CI] 1.13-4.64; P = 0.023). PT-INR after initiation of therapy significantly increased and was higher in the R group than in the E group (median value, 1.4 and 1.2, respectively; P < 0.001). Multivariate analysis using Cox proportional hazards and Fine-Gray models revealed that PT-INR after initiation of therapy was an independent risk factor of bleeding discontinuation events (HR = 4.37, 95% CI 2.57-7.41: P < 0.001). Respiratory bleeding occasionally occurs in patients receiving FXa inhibitors, and monitoring the PT-INR may need to ensure safety.

Comparison of nintedanib-induced gastrointestinal adverse events between patients with systemic sclerosis-associated interstitial lung disease and idiopathic interstitial pneumonias.

BACKGROUND: Gastrointestinal symptoms, such as diarrhea and nausea, are common adverse events associated with nintedanib. Systemic sclerosis is associated with a high prevalence of gastrointestinal symptoms that may increase with nintedanib administration. In clinical practice, we aimed to determine whether patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) experience more adverse gastrointestinal events associated with nintedanib than patients with idiopathic interstitial pneumonias (IIPs). METHODS: We retrospectively examined the clinical records of patients with SSc-ILD and IIPs newly treated with nintedanib at Kumamoto University Hospital between January 2020 and September 2022 and compared adverse events. RESULTS: In total, 27 patients with SSc-ILD and 34 with IIPs were enrolled. No significant differences were observed in the duration of nintedanib treatment. The most frequent adverse event in both groups was diarrhea, which was more frequent in the SSc-ILD group (81.5 % vs. 61.8 %, p = 0.157). Nausea was significantly more frequent in the SSc-ILD group than in the IIPs group (37.0 % vs. 11.8 %, p = 0.031). The permanent discontinuation rate of nintedanib during the study period between the two groups was not different (40.7 % vs. 32.4 %, p = 0.595). However, the most common reasons for discontinuation varied. The most frequent reason in the SSc-ILD group was nausea, due to the progression of ILD in the IIPs group. CONCLUSIONS: Patients with SSc-ILD experienced significantly more nintedanib-induced nausea than those with IIPs. Gastrointestinal adverse events are often the reason for discontinuation of nintedanib in the SSc-ILD group, which requires better management of gastrointestinal symptoms.

Interstitial Lung Disease in Adulthood Associated with Surfactant Protein C Gene Mutation in a Patient with a History of Lipoid Pneumonia in Infancy.

Mutations in the surfactant protein C gene (SFTPC) are responsible for hereditary interstitial lung disease (ILD), which is a rare disease. We herein report a patient with a clinical history of endogenous lipoid pneumonia in infancy who developed diffuse progressive pulmonary fibrosis in adulthood associated with SFTPC mutations. A surgical lung biopsy and genetic sequencing revealed fibrotic interstitial pneumonia and two SFTPC mutations (c.215G>A and c.578C>A). Based on these findings, we diagnosed the series of lung diseases as sporadic ILD caused by SFTPC mutations. Physicians should suggest genetic sequencing in patients with early-onset ILD.

Clinical impact of SUVmax of interstitial lesions in lung cancer patients with interstitial lung disease who underwent pulmonary resection.

Background: Acute exacerbation of interstitial lung disease often causes fatal respiratory deterioration in lung cancer patients with interstitial lung disease. Here, we examined whether the maximum standardized uptake value of a contralateral interstitial lesion was a predictive factor of acute exacerbation of interstitial lung disease within 30 days postoperatively in lung cancer patients with interstitial lung disease who underwent pulmonary resection. Methods: Overall, 117 consecutive lung cancer patients with interstitial lung disease who underwent pulmonary resection between August 2010 and April 2019 at the Kumamoto University Hospital were retrospectively analysed for the association between the maximum standardized uptake value of the contralateral interstitial lesions and interstitial lung disease parameters. Results: The median maximum standardized uptake value of contralateral interstitial lesions was 1.61, which was regarded as the cut-off point predictive of the incidence of acute exacerbation of interstitial lung disease. Eight patients developed postoperative acute exacerbation of interstitial lung disease. There was no significant association between the maximum standardized uptake value of the contralateral interstitial lesions and postoperative acute exacerbation of interstitial lung disease. The maximum standardized uptake value was weakly but significantly associated with lactate dehydrogenase levels (r=0.211, P=0.022), Krebs von den Lungen-6 (r=0.208, P=0.028), and % diffusing capacity for carbon monoxide (r=-0.290, P=0.002). Moreover, seven patients developed acute exacerbation of the interstitial lung disease during the clinical course after 30 postoperative days, and the incidence rate of acute exacerbation of interstitial lung disease was significantly higher in the high maximum standardized uptake value group (≥1.61) than in the low maximum standardised uptake value group (<1.61) (12.7% vs. 0%, P=0.002, Gray's test). Conclusions: Maximum standardized uptake value was not a predictor of postoperative acute exacerbation of interstitial lung disease in lung cancer patients with interstitial lung disease after pulmonary resection, but could be a predictive tool of an association with interstitial lung disease severity and activity markers.

18F-FDG uptake in accessory respiratory muscles shows the respiratory effort of patients with pleuroparenchymal fibroelastosis.

Patients with pleuroparenchymal fibroelastosis (PPFE) have severe breathlessness even with mild hypoxaemia. In patients with PPFE, accessory respiratory muscles, such as the sternocleidomastoid muscles, are used to maintain ventilation. An intense 18F-fluorodeoxyglucose uptake in accessory respiratory muscles using positron emission tomography/computed tomography reflects the strong respiratory effort of patients with PPFE.

Pathological and clinical relevance of selective recruitment of Langerhans cells in the respiratory bronchioles of smokers.

BACKGROUND: Smoking causes an influx of inflammatory cells including Langerhans cells (LCs) into the airways and lung parenchyma, thus inducing histological changes, such as emphysema and fibrosis. We examined the distribution and quantity of Langerhans cells in relation to clinical and pathological findings and explored the association between smoking and accumulation of Langerhans cells in the respiratory bronchioles. METHODS: Fifty-three patients who underwent lung resection for primary diseases, including lung cancer, were recruited. Histological and immunohistochemistry analyses were utilized to identify CD1a-positive Langerhans cells in peripheral lung specimens separated from primary lesions. Clinical characteristics, pathological changes, and distribution of CD1a-positive Langerhans cells distribution were assessed. RESULTS: Of the 53 patients, 35 were smokers and 18 were non-smokers. The number of Langerhans cells in the respiratory bronchioles was significantly increased in smokers as compared to that in non-smokers (p < 0.001). The number of Langerhans cells in smokers was significantly higher in patients with mild emphysema than in those without emphysema (p < 0.01). The high-LC group showed more frequent smoking-related histological changes, such as respiratory bronchiolitis, parenchymal fibrosis, accumulation of macrophages, and smoking-related interstitial fibrosis, than the low-LC group. However, there were no differences in the smoking indices and pulmonary functions of the groups. CONCLUSIONS: Selective accumulation of Langerhans cells in the respiratory bronchioles of smokers may lead to the development of smoking-related pathological changes.

Decrease in hemoglobin level predicts increased risk for severe respiratory failure in COVID-19 patients with pneumonia.

BACKGROUND: In December 2019, the coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), emerged in Wuhan, China, and has since spread throughout the world. This study aimed to investigate the association between the change in laboratory markers during the three days after pneumonia diagnosis and severe respiratory failure in COVID-19 patients. METHODS: Data of 23 COVID-19 patients with pneumonia, admitted to the Kumamoto City Hospital between February and April 2020 were retrospectively analyzed. RESULTS: Among the 23 patients, eight patients received mechanical ventilation (MV) (MV group), and the remaining 15 comprised the non-MV group. The levels of hemoglobin (Hb) and albumin (Alb) decreased in the MV group during the three days after pneumonia diagnosis more than in the non-MV group (median Hb: 1.40 vs. -0.10 g/dL, P = 0.015; median Alb: 0.85 vs. -0.30 g/dL, P = 0.020). Univariate logistic regression analysis showed that the decrease in Hb was associated with receiving MV care (odds ratio: 0.313, 95% confidence interval: 0.100-0.976, P = 0.045). Receiver operating characteristic curve analyses showed that the optimal cut-off value for the decrease in Hb level was -1.25 g/dL, with sensitivity and specificity values of 0.867 and 0.750, respectively. CONCLUSIONS: The decrease in Hb level during the short period after pneumonia diagnosis might be a predictor of worsening pneumonia in COVID-19 patients.

Prognostic impact of pre-existing interstitial lung disease in non-HIV patients with Pneumocystis pneumonia.

BACKGROUND: The increasing incidence of life-threatening Pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients is a global concern. Yet, no reports have examined the prognostic significance of pre-existing interstitial lung disease (ILD) in non-HIV PCP. METHODS: We retrospectively reviewed the medical records of non-HIV PCP patients with (ILD group) or without (non-ILD group) pre-existing ILD. The clinical features and outcomes of the ILD group were compared with those of the non-ILD group. Cox regression models were constructed to identify prognostic factors. RESULTS: 74 patients were enrolled in this study. The 90-day mortality was significantly higher in the ILD group than in the non-ILD group (62.5% versus 19.0%, p<0.001). In the ILD group, patients with a higher percentage of bronchoalveolar lavage fluid neutrophils had worse outcomes compared to those having a lower percentage (p=0.026). Multivariate analyses revealed that pre-existing ILD (p=0.002) and low levels of serum albumin (p=0.009) were independent risk factors for 90-day mortality. Serum levels of ß-d-glucan were significantly reduced after treatment of PCP in both groups, whereas levels of Krebs von den Lungen-6 (KL-6) significantly increased in the ILD group. In the ILD group, the 90-day mortality of patients with increasing KL-6 levels after treatment was significantly higher than those with decreasing levels (78.9% versus 0%, p=0.019). CONCLUSION: In non-HIV PCP patients, pre-existing ILD is associated with a poorer prognosis. Prophylaxis for PCP is needed in patients with pre-existing ILD under immunosuppression.

Four-meter gait speed predicts daily physical activity in patients with chronic respiratory diseases.

BACKGROUND: Physical activity measures are valuable for assessing the progression of chronic respiratory diseases. The 4-m gait speed (4MGS) test is an established functional assessment in the elderly. However, the relationship between the 4MGS and daily activity in patients with chronic respiratory diseases has not been fully understood. The present study aimed to investigate whether the 4MGS predicted daily activity, including physical activity level (PAL), in patients with chronic respiratory diseases. METHODS: We enrolled 57 patients with chronic respiratory diseases, including interstitial lung disease and chronic obstructive pulmonary disease, and evaluated the correlations between the 4MGS and various clinical parameters, including respiratory function, the 6-min walk test (6MWT), and daily activities, by using an accelerometer. Linear regression analysis was performed to identify significant predictors of daily activity. RESULTS: The 4MGS was significantly correlated with daily step counts and PAL, as well as the 6 min walk distance (r = 0.477, p < 0.001; r = 0.433, p = 0.001; and r = 0.593, p < 0.001, respectively). In the multivariate linear regression analysis, the 4MGS, % predicted forced expiratory volume in 1 s, and body mass index were independent predictors of PAL. Receiver operating characteristic analysis revealed that a 4MGS <1.07 m/s was the optimal cutoff for predicting an inactive PAL (area under the curve, 0.728; 95% confidence interval, 0.589-0.866). Patients with a slower 4MGS had significantly reduced daily activity than did those with a preserved 4MGS, despite similar modified Medical Research Council dyspnea scale measures and respiratory parameters, such as oxygenation profiles. CONCLUSIONS: The 4MGS test is a simple screening test and a useful predictor of worsening daily activity in patients with chronic respiratory diseases.

Efficacy of direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-DHP) in rapidly progressive interstitial pneumonias: results of a historical control study and a review of previous studies.

BACKGROUND: Direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-DHP) therapy has been approved for sepsis-associated acute respiratory distress syndrome, but its efficacy for other rapidly progressive interstitial pneumonias (RPIPs) is unclear. The purpose of this study was to examine the efficacy of PMX-DHP therapy for acute respiratory failure in patients with RPIPs, when compared with a historical control receiving conventional treatment without PMX-DHP. METHODS: This study comprised 77 patients with RPIPs in our institute between January 2002 and December 2015. The initial 36 patients between January 2002 and March 2007 were treated without PMX-DHP (historical control group), and the following 41 patients between April 2007 and December 2015 were treated with PMX-DHP (PMX-DHP group) once daily for two successive days concurrently with corticosteroids and/or immunosuppressive agents. The 90-day mortality and clinical factors were compared between the groups. Cox proportional hazards models were constructed to analyze 90-day mortality and identify predictors. RESULTS: The 90-day mortality rate was significantly lower in the PMX-DHP group than in the controls (41.5% versus 66.7%, p = 0.019). PMX-DHP therapy was significantly associated with mortality (hazard ratio 0.505; 95% confidence interval, 0.270-0.904; p = 0.032). There were significant differences in the serial changes in the PaO2/FiO2 ratio, SOFA score, and blood neutrophil counts from days 0-5 after PMX-DHP between the survivor and non-survivor groups ( p = 0.015, p < 0.001, p = 0.035, respectively). The improved PaO2/FiO2 ratio on day 3 significantly correlated with the change in blood neutrophil counts (rs = -0.431, p = 0.006). CONCLUSIONS: PMX-DHP therapy may be effective in RPIPs patients accompanied by acute respiratory failure and is expected to reduce mortality rates.

Favorable outcome with hemoperfusion of polymyxin B-immobilized fiber column for rapidly progressive interstitial pneumonia associated with clinically amyopathic dermatomyositis: report of three cases.

We present 3 cases of rapidly progressive interstitial pneumonia (RPIP) associated with clinically amyopathic dermatomyositis (C-ADM) that were treated with two courses of direct hemoperfusion with polymyxin B-immobilized fiber column (PMX-DHP). Despite initial treatment with high-dose corticosteroids, pulsed cyclophosphamide, and cyclosporine, the lung disease and hypoxemia deteriorated in all the patients. After PMX-DHP treatment, the PaO2/FiO2 ratio and serum LDH and KL-6 were improved, the abnormal shadows in chest high-resolution computed tomography (HRCT) scans gradually decreased, and, finally, all patients survived. These findings indicate that PMX-DHP treatment could be effective in the management of RPIP in patients with C-ADM in combination with conventional therapy.

Successful treatment of severe amiodarone pulmonary toxicity with polymyxin B-immobilized fiber column direct hemoperfusion.

Amiodarone pulmonary toxicity (APT) is the most serious side effect of amiodarone. Although severe APT, such as ARDS, is rare, mortality of severe APT is high. Polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) is a medical device that reduces blood endotoxin levels in sepsis. Recent reports have shown that PMX-DHP improves oxygenation in patients with acute exacerbation of idiopathic pulmonary fibrosis and drug-induced severe interstitial pneumonia. Here, we present a case study of a patient with severe APT treated with PMX-DHP with complete recovery. The patient rapidly developed respiratory failure and required mechanical ventilation. Despite corticosteroid pulse therapy, no clinical improvement was noted. PMX-DHP was then started, and severe respiratory failure improved with reduction of serum levels of amiodarone and its metabolite monodesethylamiodarone. The patient was weaned from mechanical ventilation and has done well without recurrence. To our knowledge, this is the first reported case of PMX-DHP therapy for severe APT. We speculate that PMX-DHP could be a new treatment strategy for severe APT.

Galectin-9 attenuates acute lung injury by expanding CD14- plasmacytoid dendritic cell-like macrophages.

RATIONALE: Galectin (Gal)-9 plays a crucial role in the modulation of innate and adaptive immunity. OBJECTIVES: To investigate whether Gal-9 plays a role in a murine acute lung injury (ALI) model. METHODS: C57BL/6 mice were pretreated with Gal-9 by subcutaneous injection 24 and 48 hours before intranasal LPS inoculation. MEASUREMENTS AND MAIN RESULTS: Gal-9 suppressed pathological changes of ALI induced by LPS. Gal-9 reduced levels of proinflammatory cytokines and chemokines, such as tumor necrosis factor (TNF)-α, IL-1ß, IL-6, and keratinocyte-derived cytokine; decreased neutrophils; and increased IL-10 and CD11b(+)Gr-1(+) macrophages in the bronchoalveolar lavage fluid of ALI mice. In Gal-9-deficient mice, pathological changes of ALI were exaggerated, and the number of neutrophils and the TNF-α level were increased. CD11b(+)Gr-1(+) cells were increased in the spleen of both Gal-9-treated and phosphate-buffered saline (PBS)-treated ALI mice, but only Gal-9 increased the ability of CCR2-expressing macrophages to migrate toward monocyte chemoattractant protein-1. Transfer of CD11b(+)Gr-1(+) macrophages obtained from Gal-9-treated mice ameliorated ALI. CD11b(+)Gr-1(+) macrophages obtained from Gal-9-treated but not PBS-treated mice suppressed TNF-α and keratinocyte-derived cytokine production from LPS-stimulated macrophages, and down-regulated Toll-like receptor-4 (TLR4) and TLR2 expression on thioglycollate-elicited macrophages. Fluorescence-activated cell-sorting analysis revealed that CD14 is negligible on CD11b(+)Gr-1(+) macrophages obtained from Gal-9-treated mice, although those from both groups resembled plasmacytoid dendritic cells (pDCs). Gal-9 down-regulated CD14 on pDC-like macrophages from PBS-treated mice independently of Gal-9/Tim-3 (T-cell immunoglobulin- and mucin domain-containing molecule-3) interaction, resulting in the acquisition of suppressive function, suggesting that the loss of CD14 by Gal-9 is critical for the suppression of pDC-like macrophages. CONCLUSIONS: Gal-9 attenuates ALI by expanding CD14(-)CD11b(+)Gr-1(+) pDC-like macrophages by preferentially suppressing macrophage functions to release proinflammatory cytokines through TLR4 and TLR2 down-regulation.

[Successful treatment of pleurodesis for seemingly intractable pleural effusion in pleural amyloidosis with rheumatoid arthritis].

We report a case of secondary amyloidosis with pleural involvement in a patient with rheumatoid arthritis. A 77-year-old man had received a diagnosis of rheumatoid arthritis 10 years previously. Bilateral pleural effusion of unknown etiology was noted 2 years prior to admission. A biopsy of the left pleura by video-assisted thoracic surgery did not reveal any evidence of the cause of his pleural effusion. The histological findings revealed chronic inflammation of the pleura on a hematoxylin-eosin (HE) stain, but treatment with an increased dose of corticosteroid did not improve his effusion. Right pneumothorax then developed. Based on the histological findings of a Congo red stain, the diagnosis was changed to pleural amyloidosis. An initial attempt at pleurodesis with OK-432 and a pleural patch with the patient's own blood was attempted but was not successful. Subsequently, pleurodesis with OK-432 and the patient's own blood improved his pleural effusion and pneumothorax. Pleural involvement in amyloidosis is extremely rare and is difficult to treat.

[Three cases of allergic bronchopulmonary mycosis due to Schizophyllum commune].

We report 3 cases of allergic bronchopulmonary mycosis (ABPM) due to Schizophyllum commune. The first patient, an 82-year-old woman, presented with atelectasis of the left upper lobe with mucoid impaction due to Schizophyllum commune. The second patient, a 53-year-old woman, presented with atelectasis of the right middle lobe with mucoid impaction due to Schizophyllum commune. The last patient, a 49-year-old woman, underwent a left lingular lobectomy with a diagnosis of lung abscess, but the diagnosis was retrospectively changed to ABPM in a later review of the findings of the surgical specimens. The diagnosis and treatment of ABPM are not well defined, and this considerably delayed our diagnosis in these three cases. We hope to establish a more definitive diagnosis and treatment for ABPM through ongoing encounters with patients.

[Clinical comparison of male and female patients with pulmonary disease caused by Mycobacterium avium complex (P-MAC)].

OBJECTIVES: The objective of this study was to clarify clinical feature of Pulmonary Mycobacterium avium complex disease (P-MAC). METHOD: The present study was performed in 120 patients with P-MAC diagnosed during the period from January 2000 to March 2007. We divided P-MAC patients into four groups by the clinical disease type and gender, and retrospectively examined the clinical characteristics. RESULTS: The subjects were 15 male (NB-M) and 71 female (NB-F) patients with nodular bronchiectatic disease (NB), and 24 male (FC-M) and 10 female (FC-F) patients with fibrocavitary disease (FC). The average age was lowest in the NB-F group (58.0 yrs), and highest in the FC-M group (65.8 yrs). There were 17 patients in the FC-M group and only two patients in the FC-F group with a history of smoking. The average body mass index (BMI) was 16.9, with the lowest value in the FC-F group. In the FC-M group, most of the patients had underlying pulmonary disease, whereas in the FC-F group, only four patients had underlying old pulmonary tuberculosis. The average anterior-posterior dimension was 75.2 mm, being lowest in the FC-F group, and more than 90 mm in the other groups. The proportion of refractory cases was lowest in the NB-M group. CONCLUSION: We thought that we were able to clarify characteristics of patients with disease caused by MAC by analyzing the types of the disease separately in men and women.

[Evaluation of KL-6 CLEIA reagent].

KL-6 is a high-molecular-weight sialylated glycoprotein, classified as a cluster 9 pulmonary cell antigens, and is a sensitive marker for the clinical diagnosis of interstitial pneumonia and its activity, especially in the acute phase. Additionally, it is necessary to diagnosis that patient was not pneumothirax, pulmonary thromboembolism and heart failure. In this study, we evaluated a new assay system based on chemiluminescence EIA (CLEIA) on a fully automated analyzer. Both plasma and serum samples were used, and the master calibration method was applied, eliminating the need for a standard curve preparation. The assay time was shortened to less than 1 hour. Good correlations were observed between this assay and conventional assay kits, y = 1.094x-6.849, r = 0.986 using 326 samples, and between serum and plasma y = 0.997x-1.211, r = 0.997 using 225 paired samples. In addition, the alteration of KL-6 concentration in patients undergoing chemotherapy treatment resulted in similar results that with conventional kits, and elevated KL-6 concentrations were observed in samples from patients with interstitial pneumonia. These results underscore the usefulness of this new assay kit as a rapid test, particularly for the medical examination of outpatients and the treatment of emergency cases in the acute phase of interstitial pneumonia.