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BACKGROUND: The diagnosis of fibrotic hypersensitivity pneumonitis (fHP) from other interstitial lung diseases, particularly idiopathic pulmonary fibrosis (IPF), is often difficult. This study aimed to examine computed tomography (CT) findings that were useful for differentiating between fHP and IPF and to develop and validate a radiological diagnostic model. METHODS: In this study, 246 patients (fHP, n = 104; IPF, n = 142) from two institutions were included and randomly divided into the test (n = 164) and validation (n = 82) groups (at a 2:1 ratio). Three radiologists evaluated CT findings, such as pulmonary fibrosis, small airway disease, and predominant distribution, and compared them between fHP and IPF using binomial logistic regression and multivariate analysis. A prognostic model was developed from the test group and validated with the validation group. RESULTS: Ground-glass opacity (GGO) with traction bronchiectasis (TB), honeycombing, hypoattenuation area, three-density pattern, diffuse craniocaudal distribution, peribronchovascular opacities in the upper lung, and random distribution were more common in fHP than in IPF. In multivariate analysis, GGO with TB, peribronchovascular opacities in the upper lung, and random distribution were significant features. The area under the curve of the fHP diagnostic model with the three aforementioned CT features was 0.733 (95% confidence interval [CI], 0.655-0.811, p < 0.001) in the test group and 0.630 (95% CI, 0.504-0.755, p < 0.047) in the validation group. CONCLUSION: GGO with TB, peribronchovascular opacities in the upper lung, and random distribution were important CT features for differentiating fHP from IPF.
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Alveolitis Alérgica Extrínseca , Fibrosis Pulmonar Idiopática , Tomografía Computarizada por Rayos X , Humanos , Alveolitis Alérgica Extrínseca/diagnóstico por imagen , Alveolitis Alérgica Extrínseca/diagnóstico , Fibrosis Pulmonar Idiopática/diagnóstico por imagen , Fibrosis Pulmonar Idiopática/patología , Tomografía Computarizada por Rayos X/métodos , Diagnóstico Diferencial , Masculino , Femenino , Anciano , Persona de Mediana EdadRESUMEN
Idiopathic pulmonary fibrosis (IPF) is the archetypal interstitial lung disease. It is a chronic progressive condition that is challenging to manage as the clinical course of the disease is often difficult to predict. The prevalence of IPF is rising globally and in Japan, where it is estimated to affect 27 individuals per 100,000 of the population. Greater patient numbers and the poor prognosis associated with IPF diagnosis mean that there is a growing need for disease management approaches that can slow or even reverse disease progression and improve survival. Considerable progress has been made in recent years, with the approval of two antifibrotic therapies for IPF (pirfenidone and nintedanib), the availability of Japanese treatment guidelines, and the creation of global and Japanese disease registries. Despite this, significant unmet needs remain with respect to the diagnosis, treatment, and management of this complex disease. Each of these challenges will be discussed in this review, including making a timely and differential diagnosis of IPF, uptake and adherence to antifibrotic therapy, patient access to pulmonary rehabilitation, lung transplantation and palliative care, and optimal strategies for monitoring and staging disease progression, with a particular focus on the status in Japan. In addition, the review will reflect upon how ongoing research, clinical trials of novel therapies, and technologic advancements (including artificial intelligence, biomarkers, and genomic classification) may help address these challenges in the future.
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Progresión de la Enfermedad , Fibrosis Pulmonar Idiopática , Indoles , Trasplante de Pulmón , Piridonas , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/terapia , Humanos , Japón/epidemiología , Indoles/uso terapéutico , Piridonas/uso terapéutico , Cuidados Paliativos , Diagnóstico Diferencial , Guías de Práctica Clínica como Asunto , Antifibróticos/uso terapéutico , Prevalencia , Biomarcadores , Sistema de RegistrosRESUMEN
Background: The specific long-term sequela of coronavirus disease 2019 (COVID-19), also known as long COVID of the Omicron variant remain unclear, due to a lack of cohort studies that include non-COVID patients with cold-like symptoms. The study was conducted to examine specific sequelae symptoms after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, which is considered the Omicron variant, compared with patients who were never-infected. Methods: In this retrospective cohort study, we sent questionnaires in November 2022, targeting those who visited our fever outpatient unit of a single institution from July to September 2022. SARS-CoV-2 infection status was determined by SARS-CoV-2 polymerase chain reaction (PCR) test results during the study period collected in electronic medical records. Clinical characteristics at 30 days or more since the date of SARS-CoV-2 PCR test were assessed by the questionnaires. Multiple logistic regression was performed to investigate the independent association between SARS-CoV-2 infection and possible sequelae symptoms. Results: In total, valid responses were received from 4,779 patients (mean age: 41.4 years, standard deviation: 19.8 years old). Among them, 3,326 (69.6%) and 1,453 (30.4%) were SARS-CoV-2 PCR test positive and never-infected, respectively. We found that patients with SARS-CoV-2 infection were more likely to have a loss of taste or smell [odds ratio (OR) 4.55, 95% confidence interval (CI): 1.93, 10.71], hair loss (OR 3.19, 95% CI: 1.67, 6.09), neurocognitive symptoms (OR 1.95, 95% CI: 1.43, 2.65), and respiratory symptoms (OR 1.23, 95% CI: 1.03, 1.47) than never-infected patients. SARS-CoV-2 infection was not associated with common cold symptoms, chronic physical distress, or diarrhea as sequelae symptoms. Further, SARS-CoV-2 vaccination showed protective effects on sequelae of loss of taste or smell and hair loss. Conclusions: Loss of taste or smell, hair loss, neurocognitive symptoms, and respiratory symptoms were found to be specific sequelae of the SARS-CoV-2 Omicron variant. It is important not to miss these symptoms that follow SARS-CoV-2 infection and to recognize and manage the long COVID.
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Lymphoid proliferations and lymphomas associated with immune deficiency and dysregulation (LP/L-IDD) are rare entities associated with the use of immunosuppressive drugs (ISD) for autoimmune conditions. Composite lymphomas, featuring both B-cell and T-cell lymphomas, are infrequent, and their occurrence as LP/L-IDD is rare. We herein report the case of a 70-year-old man with right pleural effusion and lymphadenopathy, who was treated with infliximab for sarcoidosis and ankylosing spondylitis. A biopsy revealed a composite lymphoma of DLBCL and PTCL-NOS. CHOP chemotherapy led to significant remission. This case report emphasizes the need to consider lymphoma in patients with autoimmune diseases such as sarcoidosis and ankylosing spondylitis, especially those treated with ISDs.
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BACKGROUND: Immune-checkpoint inhibitors (ICIs) often cause immune-related adverse events (irAEs). The spectrum of irAEs and their managements has been partially clarified, however the knowledge on time-course of irAEs is not well understood. METHODS: A retrospective study based on the medical record was performed. The study subjects were consisting of patients with various types of solid tumors for whom ICIs (nivolumab, pembrolizumab, durvalumab, atezolizumab, nivolumab plus ipilimumab) were used between April 2016 and October 2021. We focused on irAEs developed more than 1-year after commencement ICIs (delayed irAE group) and compared with irAEs developed within 1-year (non-delayed irAE group) in terms of types and severity of irAEs. RESULTS: A total of 336 patients were enrolled in the study. Eighty-eight patients (26.2%) developed irAEs and 248 did not. Most of the patients developing irAEs were treated using PD-L1/PD-1 inhibitors. Eighty-one patients (24.1%) in non-delayed irAE group and 7 patients (2.1%) in delayed irAE group developed irAEs. The median onset of irAEs in the delayed irAE group was 18.6 months (range: 13.5-24.3). The types of irAEs observed in delayed irAE group were dermatitis (2 cases), pneumonitis (2 cases), nephritis (1 case), arthritis (1 case), and gastritis (1 case). The severity of irAEs was almost mild (≤G2), but one patient (.3%) developed G3 nephritis. CONCLUSION: PD-L1/PD-1 inhibitors frequently caused various irAEs but their severities were mostly tolerable. Few patients developed delayed irAE with mild toxities.
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Neoplasias , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Adulto , Inmunoterapia/efectos adversos , Inmunoterapia/métodos , Anciano de 80 o más Años , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnósticoRESUMEN
BACKGROUND: The emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has increased the incidence of community-onset MRSA infection. Respiratory tract infections caused by MRSA has been noted for their severity; however, repeated relapses that require extended antibiotic therapy are rare. CASE PRESENTATION: We report a case of relapsing bronchopneumonia caused by CA-MRSA in a 56-year-old man. The patient responded to antibiotics, but repeatedly relapsed after stopping treatment. MRSA was consistently isolated from airway specimens during each relapse. Extended oral antibiotic treatment with trimethoprim/sulfamethoxazole (TMP/SMX) for 6 months achieved infection control. Whole-genome sequencing of the isolated strain revealed that the causative agent was sequence type (ST)1/staphylococcal cassette chromosome mec (SCCmec) type IVa, a clone that is rapidly increasing in Japan. DISCUSSION AND CONCLUSIONS: This patient had an unusual course of MRSA bronchopneumonia with repeated relapses. Although the choice of antibiotics for long-term use in MRSA respiratory tract infections has not been well established, TMP/SMX was effective and well tolerated for long-term therapy in this case. The clinical course of infections related to the rapid emerging clone, ST1/SCCmec type IVa warrants further attention.
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Bronconeumonía , Infecciones Comunitarias Adquiridas , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Masculino , Humanos , Persona de Mediana Edad , Staphylococcus aureus Resistente a Meticilina/genética , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Bronconeumonía/diagnóstico , Bronconeumonía/tratamiento farmacológico , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/epidemiología , Antibacterianos/uso terapéutico , Recurrencia , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/epidemiologíaRESUMEN
INTRODUCTION: Prostaglandin D2 (PGD2), which is produced mainly by Th2 cells and mast cells, promotes a type-2 immune response by activating Th2 cells, mast cells, eosinophils, and group 2 innate lymphoid cells (ILC2s) via its receptor, chemoattractant receptor-homologous molecules on Th2 cells (CRTH2). However, the role of CRTH2 in models of airway inflammation induced by sensitization without adjuvants, in which both IgE and mast cells may play major roles, remain unclear. METHODS: Wild-type (WT) and CRTH2-knockout (KO) mice were sensitized with ovalbumin (OVA) without an adjuvant and then challenged intranasally with OVA. Airway inflammation was assessed based on airway hyperresponsiveness (AHR), lung histology, number of leukocytes, and levels of type-2 cytokines in the bronchoalveolar lavage fluid (BALF). RESULTS: AHR was significantly reduced after OVA challenge in CRTH2 KO mice compared to WT mice. The number of eosinophils, levels of type-2 cytokines (IL-4, IL-5, and IL-13) in BALF, and IgE concentration in serum were decreased in CRTH2 KO mice compared to WT mice. However, lung histological changes were comparable between WT and CRTH2 KO mice. CONCLUSION: CRTH2 is responsible for the development of asthma responses in a mouse model of airway inflammation that features prominent involvement of both IgE and mast cells.
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Citocinas , Ratones Noqueados , Ovalbúmina , Receptores Inmunológicos , Receptores de Prostaglandina , Animales , Receptores de Prostaglandina/genética , Receptores de Prostaglandina/metabolismo , Receptores Inmunológicos/metabolismo , Receptores Inmunológicos/genética , Ratones , Ovalbúmina/inmunología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Líquido del Lavado Bronquioalveolar/inmunología , Líquido del Lavado Bronquioalveolar/citología , Pulmón/patología , Pulmón/inmunología , Asma/inmunología , Asma/patología , Asma/metabolismo , Células Th2/inmunología , Hipersensibilidad Respiratoria/inmunología , Hipersensibilidad Respiratoria/metabolismo , Hipersensibilidad Respiratoria/patología , Eosinófilos/inmunología , Hiperreactividad Bronquial/inmunología , Hiperreactividad Bronquial/etiología , Mastocitos/inmunología , Mastocitos/metabolismo , Inflamación/inmunología , Ratones Endogámicos C57BLRESUMEN
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with a poor prognosis and an unknown cause that generally progresses to pulmonary fibrosis and leads to irreversible tissue alteration. The "Guidelines for the treatment of idiopathic pulmonary fibrosis 2017," specializing in the treatment of IPF for the first time in Japan and presenting evidence-based standard treatment methods suited to the state of affairs in Japan, was published in 2017, in line with the 2014 version of "Formulation procedure for Minds Clinical Practice Guidelines." Because new evidence had accumulated, we formulated the "Guidelines for the treatment of Idiopathic Pulmonary Fibrosis 2023 (revised 2nd edition)." While keeping the revision consistent with the ATS/ERS/JRS/ALAT IPF treatment guidelines, new clinical questions (CQs) on pulmonary hypertension were added to the chronic stage, in addition to acute exacerbation and comorbid lung cancer, which greatly affect the prognosis but are not described in the ATS/ERS/JRS/ALAT IPF guidelines. Regarding the advanced stages, we additionally created expert consensus-based advice for palliative care and lung transplantation. The number of CQs increased from 17 in the first edition to 24. It is important that these guidelines be used not only by respiratory specialists but also by general practitioners, patients, and their families; therefore, we plan to revise them appropriately in line with ever-advancing medical progress.
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Fibrosis Pulmonar Idiopática , Enfermedades Pulmonares Intersticiales , Neoplasias Pulmonares , Humanos , Japón/epidemiología , Fibrosis Pulmonar Idiopática/terapia , PronósticoRESUMEN
The serine-threonine protein kinase B-RAF (BRAF) fusions are rarely observed in non-small cell lung cancer (NSCLC) accounting for less than 1%, and therapeutic evidence for molecular-targeted drugs is lacking, unlike for BRAF V600E mutation by RAF and MEK inhibitors. A 75-year-old female patient with no smoking history and mild renal dysfunction developed recurrent lung adenocarcinoma and was initially treated with pembrolizumab immunotherapy followed by chemotherapy using docetaxel showing a certain efficacy but the disease finally progressed. Comprehensive genome profiling showed a novel SLC44A1-BRAF fusion and the tumor progression was controlled with the MEK inhibitor trametinib. Because of the rarity of NSCLC with BRAF fusion, the description of this case would be helpful for the treatment strategy for such tumors.
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Background: In interstitial pneumonia (IP)-associated lung cancer, immune checkpoint inhibitor pneumonitis (ICIP) is common with immune checkpoint inhibitor (ICI) treatment. The purpose of the present study was to clarify the safety and efficacy of ICI treatment for patients with lung cancer with IP. Methods: This multicentre retrospective observational study was conducted from June 2016 to December 2020 in patients with primary lung cancer with IP who received ICI treatment. Results: A total of 200 patients (median age 70â years; male/female, 176/24) were enrolled from 27 institutions. ICIP occurred in 61 patients (30.5%), pneumonitis grades 3-5 in 32 patients (15.5%) and death in nine patients (4.5%). The common computed tomography pattern of ICIP was organising pneumonia in 29 patients (47.5%). Subsequently, diffuse alveolar damage (DAD) pattern was observed in 19 patients (31.1%) who had a significantly worse prognosis than those with a non-DAD pattern (median progression-free survival (PFS) 115â days versus 226â days, p=0.042; median overall survival (OS) 334â days versus 1316â days, p<0.001). Immune-related adverse events (irAEs) occurred in approximately 50% of patients. Patients with irAEs (n=100) had a better prognosis than those without irAEs (n=100) (median PFS 200â days versus 77â days, p<0.001; median OS 597â days versus 390â days p=0.0074). The objective response rate and disease control rate were 41.3% and 68.5%, respectively. Conclusions: Although ICI treatment was effective for patients with lung cancer with IP, ICIP developed in approximately 30% of patients. Patients with irAEs had a significantly better PFS and OS than those without irAEs.
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INTRODUCTION: The International Agency for Research on Cancer has classified passive smoking (PS) or secondhand smoke exposure as a group 1 carcinogen linked to lung cancer. However, in contrast to active smoking, the mutagenic properties of PS remain unclear. METHODS: A consecutive cohort of 564 lung adenocarcinoma samples from female never-smokers, who provided detailed information about their exposure to PS during adolescence and in their thirties through a questionnaire, was prepared. Of these, all 291 cases for whom frozen tumor tissues were available were subjected to whole exome sequencing to estimate tumor mutational burden, and the top 84 cases who were exposed daily, or not, to PS during adolescence, in their thirties or in both periods, were further subjected to whole genome sequencing. RESULTS: A modest yet statistically significant increase in tumor mutational burden was observed in the group exposed to PS compared with the group not exposed to PS (median values = 1.44 versus 1.29 per megabase, respectively; p = 0.020). Instead of inducing driver oncogene mutations, PS-induced substantial subclonal mutations exhibiting APOBEC-type signatures, including SMAD4 and ADGRG6 hotspot mutations. A polymorphic APOBEC3A/3B allele-specific to the Asian population that leads to up-regulated expression of APOBEC3A accentuated the mutational load in individuals exposed daily to PS during adolescence. CONCLUSIONS: This study reveals that PS-induced mutagenesis can promote lung carcinogenesis. The APOBEC3A/3B polymorphism may serve as a biomarker for identifying passive nonsmoking individuals at high risk of developing lung cancer.
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Neoplasias Pulmonares , Contaminación por Humo de Tabaco , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/inducido químicamente , Contaminación por Humo de Tabaco/efectos adversos , Femenino , Carcinogénesis/genética , Mutagénesis , Persona de Mediana Edad , Adulto , Mutación , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , AncianoRESUMEN
BACKGROUND: Exposure assessment is integral to the diagnosis of hypersensitivity pneumonitis (HP). Although the clinical relevance of exposed antigens is essential for the assessment, many of the previous guidelines or reports have only evaluated simple exposure histories or immunological tests. To overcome this problem, the Exposure Assessment Form (EAF) was developed as an assessment tool for classifying the exposure grade from G0 to G4. The EAF was modified from the description in the Japanese clinical practice guide 2022 for HP published by the Japanese Respiratory Society. METHODS: One hundred and seventy-two consecutive patients with interstitial lung disease who underwent multidisciplinary discussion (MDD) at our hospital were retrospectively examined. We assessed whether the use of the EAF improved the diagnostic performance of the international guideline of HP. We also evaluated whether the exposure grade affected the prognosis of HP. RESULTS: Even when a HP diagnosis was made with a confidence of 70% or higher according to the international guideline, less than half of these cases resulted in a final diagnosis of HP when the exposure grades were lower than G3. When the result of the EAF was integrated into the exposure definition of the international guideline, the specificity of the diagnostic performance improved, while sensitivity was maintained. Furthermore, HP patients with an exposure grade of G3 or higher showed a tendency to take a longer time to initiate medication. CONCLUSIONS: This is the first study to evaluate the clinical relevance of possible antigens using the EAF. Assessing the exposure grade prevents overdiagnosis and improves the diagnostic performance of the international guideline.
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Alveolitis Alérgica Extrínseca , Enfermedades Pulmonares Intersticiales , Humanos , Estudios Retrospectivos , Relevancia Clínica , Alveolitis Alérgica Extrínseca/diagnóstico , Enfermedades Pulmonares Intersticiales/diagnóstico , AntígenosRESUMEN
We herein report a rare case of hypersensitivity pneumonitis (HP) that was initially demonstrated as solitary pure ground-glass opacity (GGO) on chest computed tomography (CT). A 51-year-old woman with a history of breast cancer underwent follow-up CT, which revealed solitary pure GGO. The patient developed exertional dyspnea after two years, and CT revealed diffuse centrilobular nodules in addition to GGO, which had increased in size. An antigen avoidance test was performed to diagnose HP, leading to the resolution of CT abnormalities, including the GGO. Our findings suggested that nonfibrotic HP can present as solitary pure GGO.
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BACKGROUND/OBJECTIVES: Obesity, defined by body mass index (BMI), is a well-known risk factor for the severity of coronavirus disease 2019 (COVID-19). Adipose tissue distribution has also been implicated as an important factor in the body's response to infection, and excess visceral fat (VF), which is prevalent in Japanese, may contribute significantly to the severity. Therefore, this study aimed to evaluate the association of obesity and VF with COVID-19 severe illness in Japan. SUBJECTS/METHODS: This retrospective cohort study involved 550 COVID-19 patients admitted to a tertiary care hospital with BMI and body composition data, including VF. The primary endpoint was severe illness, including death, due to COVID-19 during hospitalization. Logistic regression analysis was applied to examine the quartiles of BMI and VF on severe illness after adjusting for covariates such as age, sex, subcutaneous fat, paraspinal muscle radiodensity, and comorbidities affecting VF (COPD, cancer within 5 years, immunosuppressive agent use). RESULTS: The median age was 56.0 years; 71.8% were males. During hospitalization, 82 (14.9%) experienced COVID-19 severe illness. In the multivariate logistic regression analysis, Q4 of BMI was not significantly associated with severe illness compared to Q1 of BMI (OR 1.03; 95% CI 0.37-2.86; p = 0.95). Conversely, Q3 and Q4 of VF showed a higher risk for severe illness compared to Q1 of VF (OR 2.68; 95% CI 1.01-7.11; p = 0.04, OR 3.66; 95% CI 1.30-10.26; p = 0.01, respectively). Stratified analysis by BMI and adjusted for covariates showed the positive association of VF with severe illness only in the BMI < 25 kg/m2 group. CONCLUSIONS: High BMI was not an independent risk factor for COVID-19 severe illness in hospitalized patients in Japan, whereas excess VF significantly influenced severe illness, especially in patients with a BMI < 25 kg/m2.
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Índice de Masa Corporal , COVID-19 , Hospitalización , Grasa Intraabdominal , SARS-CoV-2 , Humanos , Masculino , COVID-19/epidemiología , COVID-19/complicaciones , Femenino , Persona de Mediana Edad , Japón/epidemiología , Estudios Retrospectivos , Grasa Intraabdominal/diagnóstico por imagen , Hospitalización/estadística & datos numéricos , Anciano , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto , Pandemias , Comorbilidad , Obesidad/epidemiología , Obesidad/complicacionesRESUMEN
An inhibitor of plasminogen activator inhibitor (PAI)-1, TM5614, inhibited thrombosis, inflammation, and fibrosis in several experimental mouse models. To evaluate the efficacy and safety of TM5614 in human COVID-19 pneumonia, phase IIa and IIb trials were conducted. In an open-label, single-arm trial, 26 Japanese COVID-19 patients with mild to moderate pneumonia were treated with 120-180 mg of TM5614 daily, and all were discharged without any notable side effects. Then, a randomized, double-blind, placebo-controlled trial was conducted in Japanese COVID-19 patients with mild to moderate pneumonia. The number of study participants was set to be 50 in each arm. Even after extension of the enrollment period, the number of study participants did not reach the initially intended sample size, and 75 patients were enrolled in the study. The total oxygenation scale from Day 1 to Day 14 as the primary endpoint was 1.5 in the TM5614 group vs 4.0 in the placebo group (p = 0.22), and the number of days of oxygen administration required as the secondary endpoint was 2.0 days in the TM5614 group vs 3.5 days in the placebo group (p = 0.34). Further studies will be necessary to verify the efficacy of PAI-1 inhibition for the treatment of COVID-19 pneumonia.Clinical trial registration: Two studies were conducted: a prospective, multicenter, open-label phase II study at https://jrct.niph.go.jp (jRCT2021200018) (First registration date 18/08/2020) and a prospective, multicenter, randomized, double-blind, placebo-controlled, phase II study at https://jrct.niph.go.jp (jRCT2021210006) (First registration date 28/05/2021).
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COVID-19 , Humanos , Animales , Ratones , SARS-CoV-2 , Inhibidor 1 de Activador Plasminogénico , Estudios Prospectivos , Pulmón , Método Doble Ciego , Resultado del TratamientoRESUMEN
Considering recently published two guidelines for the diagnosis of hypersensitivity pneumonitis (HP), the Japanese Respiratory Society (JRS) has now published its own Japanese clinical practice guide for HP. Major types of HP in Japan include summer-type, home-related, bird-related, farmer's lung, painter's lung, humidifier lung, and mushroom grower's lung. Identifying causative antigens is critical for increasing diagnostic confidence, as well as improving prognosis through appropriate antigen avoidance. This guide proposes a comprehensive antigen questionnaire including the outbreak sources reported in Japan. Drawing on the 2021 CHEST guideline, this guide highlights the antigen identification confidence level and adaptations for environmental surveys. The detection of specific antibodies against causative antigens is an important diagnostic predictor of HP. In Japan, the assessments of bird-specific IgG (pigeons, budgerigars) and the Trichosporon asahii antibody are covered by medical insurance. Although this guide adopts the 2020 ATS/JRS/ALAT guideline diagnostic criteria based on the combination of imaging findings, exposure assessment, bronchoalveolar lavage lymphocytosis, and histopathological findings, it added some annotations to facilitate the interpretation of the content and correlate the medical situation in Japan. It recommends checking biomarkers; seasonal changes in the KL-6 concentration (increase in winter for bird-related HP/humidifier lung and in summer for summer-type HP) and high KL-6 concentrations providing a basis for the suspicion of HP. Antigen avoidance is critical for disease management of HP. This guide also addresses the pharmacological management of HP, highlighting the treatment strategy for fibrotic HP including combination therapies with anti-inflammatory/immunosuppressive and antifibrotic drugs.
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Alveolitis Alérgica Extrínseca , Humanos , Japón/epidemiología , Alveolitis Alérgica Extrínseca/diagnóstico , Alveolitis Alérgica Extrínseca/terapia , Pulmón/patología , Lavado Broncoalveolar , BiomarcadoresRESUMEN
BACKGROUND: Allergen immunotherapy (AIT) is the only disease-modifying treatment for immunoglobulin (Ig) E-mediated allergy. Owing to the high prevalence and early onset of hay fever and pollen-food allergy syndrome (PFAS), a safer and simpler treatment method than conventional AIT is needed. To develop a local nasal immunotherapy using an ointment containing hypoallergenic pollen and assess its efficacy in mice and healthy humans. METHODS: Hypoallergenicity was achieved by combining pollen and galactomannan through the Maillard reaction to create birch pollen-galactomannan conjugate (BP-GMC). The binding of galactomannan to Bet v 1 was confirmed using electrophoresis and Western blotting (WB). Binding of specific IgE antibodies to BP-GMC was verified using enzyme-linked immunosorbent assay (ELISA) and basophil activation test (BAT). The localization of BP-GMC absorption was confirmed using a BALB/c mouse model. BP-GMC mixed with white petrolatum was intranasally administered to 10 healthy individuals (active drugs, 8; placebo, 2) for 14 days. RESULTS: In electrophoresis and WB, no 17-kDa band was observed. In ELISA and BAT, BP-GMC did not react to specific IgE but was bound to IgA and IgG. In the mouse model, BP-GMC was detected in nasopharyngeal-associated lymphoid tissues. In the active drug group, the salivary-specific IgA level significantly increased on day 15 (p = 0.0299), while the serum-specific IgG level significantly increased on day 85 (p = 0.0006). CONCLUSIONS: The BP-GMC ointment rapidly produced antagonistic antibodies against IgE; it is safe and easy to use and might serve as a therapeutic antigen for hay fever and PFAS.
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Fluorocarburos , Hipersensibilidad a los Alimentos , Galactosa/análogos & derivados , Mananos , Rinitis Alérgica Estacional , Humanos , Animales , Ratones , Rinitis Alérgica Estacional/terapia , Alérgenos , Betula , Antígenos de Plantas , Pomadas , Polen , Inmunoglobulina E , Desensibilización Inmunológica , Inmunoglobulina G , Inmunoglobulina ARESUMEN
Nontuberculous mycobacterial (NTM) infection sometimes leads to the development of pulmonary artery aneurysm (PAA), a rare but life-threatening complication. We herein report a 64-year-old woman with a history of NTM infection who presented with severe hemoptysis. Computed tomography revealed a ruptured PAA, which was treated successfully with pulmonary artery embolization. Subsequent right total pneumonectomy was performed to control infection. This case emphasizes the need to consider PAA in patients with NTM infection who present with hemoptysis. Early detection and appropriate management are critical for preventing this fatal complication.
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Aneurisma , Infecciones por Mycobacterium no Tuberculosas , Malformaciones Vasculares , Femenino , Humanos , Persona de Mediana Edad , Hemoptisis/etiología , Arteria Pulmonar/diagnóstico por imagen , Infecciones por Mycobacterium no Tuberculosas/complicaciones , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/terapia , Aneurisma/complicaciones , Aneurisma/diagnóstico por imagen , Aneurisma/cirugía , Malformaciones Vasculares/complicaciones , Micobacterias no TuberculosasRESUMEN
OBJECTIVES: To compare the [18F]FDG PET/CT findings of untreated sarcoidosis and malignant lymphoma (ML) and develop convolutional neural network (CNN) models to differentiate between these diseases using maximum intensity projection (MIP) [18F]FDG PET images. METHODS: We retrospectively collected data on consecutive patients newly diagnosed with sarcoidosis and ML who underwent [18F]FDG PET/CT before treatment. Two nuclear radiologists reviewed the images. CNN models were created using MIP PET images and evaluated with k-fold cross-validation. The points of interest were visualized using gradient-weighted class activation mapping (Grad-CAM). RESULTS: A total of 56 patients with sarcoidosis and 62 patients with ML were included. Patients with sarcoidosis had more prominent FDG accumulation in the mediastinal lymph nodes and lung lesions, while those with ML had more prominent accumulation in the cervical lymph nodes (all p < 0.001). For the mediastinal lymph nodes, sarcoidosis patients had significant FDG accumulation in the level 2, 4, 7, and 10 lymph nodes (all p < 0.01). Otherwise, the accumulation in ML patients tended to be in the level 1 lymph nodes (p = 0.08). The CNN model using frontal and lateral MIP images achieved an average accuracy of 0.890 (95% CI: 0.804-0.977), a sensitivity of 0.898 (95% CI: 0.782-1.000), a specificity of 0.907 (95% CI: 0.799-1.000), and an area under the curve of 0.963 (95% CI: 0.899-1.000). Grad-CAM showed that the model focused on the sites of abnormal FDG accumulation. CONCLUSIONS: CNN models based on differences in FDG accumulation sites archive high performance in differentiating between sarcoidosis and ML. CLINICAL RELEVANCE STATEMENT: We developed a CNN model using MIP images of [18F]FDG PET/CT to distinguish between sarcoidosis and malignant lymphoma. It achieved high performance and could be useful in diagnosing diseases with involvement across organs and lymph nodes. KEY POINTS: ⢠There are differences in FDG distribution when comparing whole-body [18F]FDG PET/CT findings in patients with sarcoidosis and malignant lymphoma before treatment. ⢠Convolutional neural networks, a type of deep learning technique, trained with maximum-intensity projection PET images from two angles showed high performance. ⢠A deep learning model that utilizes differences in FDG distribution may be helpful in differentiating between diseases with lesions that are characteristically widespread among organs and lymph nodes.
Asunto(s)
Linfoma , Sarcoidosis , Humanos , Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Retrospectivos , Linfoma/diagnóstico por imagen , Redes Neurales de la Computación , Sarcoidosis/diagnóstico por imagenRESUMEN
BACKGROUND: Summer-type hypersensitivity pneumonitis (SHP) has been reported to occur during warm and humid summer seasons in Japan; however, the effect of weather conditions on SHP remains unknown. Anti-Trichosporon asahii antibody (TaAb) test is highly specific and useful for the diagnosing SHP. Therefore, we aimed to investigate the impact of weather conditions on SHP by examining the relationship between the positivity rate of TaAb and warm and humid days. METHODS: TaAb test data from June 2013 to June 2020 were obtained from major commercial laboratories to determine the number of samples and positivity rate of TaAb by prefecture. Using the Japan Meteorological Agency database, we counted the warm and humid days (maximum temperature ≥25 °C and average humidity ≥80 %) for each prefecture. Negative binomial regression was employed to examine the relationship between the positivity rate of TaAb and the number of warm and humid days per month. RESULTS: A total of 79,211 samples and 7626 positive samples (9.6 %) were identified. We found that the number of warm and humid days, 1 or 2 months prior to testing for TaAb, was associated with the positivity rate of the test. An increase in the positivity rate by 1.6 % and 2.9 % was observed with every 1-day increase in warm and humid days 1 month and 2 months before the test, respectively. CONCLUSIONS: Our TaAb analysis revealed a significant increase in TaAb positivity 1 or 2 months after periods of warm and humid days.