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BACKGROUND: Frailty is a geriatric syndrome of age-related physiological decline, which is associated with higher mortality and decreased healthy life expectancy, and muscle weakness is one of the presentations of frailty. We investigated an association between lifetime oral corticosteroid (OCS) exposure with frailty and muscle weakness among elderly patients with asthma. METHODS: We studied 203 consecutive elderly outpatients with asthma aged ≥60 years old. They were classified into three groups according to their cumulative lifetime OCS dose (lifetime non-users, lower-dose users, and higher-dose users), which was retrospectively estimated from the response to a structured questionnaire. The prevalence of frailty determined by the Kihon Checklist was compared between the three groups. Hand-grip strength, and lean mass index were also measured as markers of muscle strength. RESULTS: Thirty-seven percent of the patients studied were considered frail. Higher cumulative lifetime OCS exposure was associated with a significantly higher prevalence of frailty (33% in lifetime non-users, 59% in lower-dose users, and 68% in higher-dose users; P for trend <0.005). This was also associated with lower hand-grip strength in both sexes (P for trend; 0.012 in men, and 0.020 in women), and lower lean mass index in men (P for trend 0.002). However, current doses of OCS were not significantly associated with these outcomes. CONCLUSIONS: Cumulative lifetime OCS exposure was associated with a higher prevalence of frailty and muscle weakness. These findings emphasize the importance of minimizing lifetime OCS exposure for the prolongation of healthy life expectancy in patients with asthma.
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Asma , Fragilidade , Idoso , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Fragilidade/epidemiologia , Idoso Fragilizado , Estudos Retrospectivos , Avaliação Geriátrica , Debilidade Muscular/epidemiologia , Asma/tratamento farmacológico , Asma/epidemiologia , Corticosteroides/efeitos adversosRESUMO
BACKGROUND: Chronic spontaneous urticaria (CSU) is a common mast cell-driven disease, presenting with wheals, angioedema, or both. Sleep-disordered breathing (SDB) is also a common condition and contributes to various diseases by causing chronic inflammation. Recent studies have suggested an association between CSU and SDB. METHODS: To determine the association between the severity of SDB and that of CSU, we studied consecutive patients with CSU who visited the Sagamihara National Hospital allergy department or dermatology department between April 1 and October 31, 2018. The severity of CSU and SDB was evaluated based on the urticaria activity score 7 (UAS7) and peripheral arterial tone apnea-hypopnea index (pAHI) derived from out-of-center sleep testing (OCST) findings, respectively; their correlation was examined. RESULTS: Of the 37 patients studied, 19 had symptom-free-to-mild CSU (UAS7 ≤15) and 18 had moderate-to-severe CSU (UAS7 ≥16). The pAHI in the latter group was significantly higher than that in the former group (18 vs. 4.2, p = 0.001). In multivariate logistic analysis, moderate-to-severe SDB (pAHI ≥15) was significantly associated with moderate-to-severe CSU even after adjusting for the BMI (adjusted odds ratio 22 [95% confidence interval, 1.7-285]). CONCLUSIONS: The severity of SDB is correlated with that of CSU independently of the BMI. Physicians should consider comorbid SDB when treating patients with CSU.
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Urticária Crônica/complicações , Síndromes da Apneia do Sono/congênito , Adulto , Causalidade , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Síndromes da Apneia do Sono/diagnósticoRESUMO
OBJECTIVE: To assess the effectiveness of low-dose mepolizumab as an add-on therapy for treating peripheral neurological symptoms in eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: We prospectively studied 13 EGPA patients with conventional treatment-resistant peripheral neuropathy. Their symptoms (pain, numbness, and muscle weakness) were assessed on a visual analogue scale (VAS) before and after 12 months of mepolizumab therapy (100 mg every 4 weeks). Peripheral eosinophil levels and several biomarkers including urinary levels of eosinophil-derived neurotoxin (EDN) were measured before and after therapy. RESULTS: VAS scores for pain and numbness significantly improved after 12 months of mepolizumab therapy (from 67.0 to 48.0, P = 0.012, and from 67.0 to 51.0, P = 0.017, respectively). However, the VAS score for muscle weakness did not improve (P = 0.36). There were significant correlations between treatment-related changes in urinary EDN levels from baseline to 6 months later and percent changes in the VAS scores of pain and numbness (r = 0.75, P = 0.020; r = 0.88, P = 0.002). CONCLUSIONS: Treatment-resistant peripheral neuropathy in EGPA was significantly improved by low-dose mepolizumab, and effectiveness was correlated with decreased urinary EDN. Because the possibility of a placebo effect cannot be formally excluded, placebo-controlled studies will be required in the future.
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Síndrome de Churg-Strauss , Granulomatose com Poliangiite , Doenças do Sistema Nervoso Periférico , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome de Churg-Strauss/tratamento farmacológico , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Doenças do Sistema Nervoso Periférico/complicações , Doenças do Sistema Nervoso Periférico/tratamento farmacológicoAssuntos
Anisaquíase , Anisakis , Hipersensibilidade Alimentar , Hipersensibilidade , Animais , Humanos , Japão/epidemiologia , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/epidemiologia , Alimentos Marinhos/efeitos adversos , Estudos Retrospectivos , Anisaquíase/diagnóstico , Anisaquíase/epidemiologiaRESUMO
The reversed halo sign was initially reported as a representative computed tomography scan finding of cryptogenic organizing pneumonia. Since then, however, it has been reported in various diseases and is now considered a nonspecific finding. However, there are no cases of humidifier lung with the reversed halo sign. An 82-year-old Japanese male patient presented with moving difficulties 48 days after starting darolutamide treatment for prostate cancer. He was admitted to the hospital due to acute pneumonia, which presented as bilateral extensive nonsegmental ground-glass opacities in the peripheral regions and extensive areas of ground-glass opacity with a circumferential halo of consolidation, with the reversed halo sign on computed tomography scan. After darolutamide discontinuation with the concomitant administration of antibiotics, the patient's pneumonia improved, and he was discharged from the hospital. However, within a few days, he was again admitted to the hospital due to pneumonia. He was found to have been using an ultrasonic humidifier at home and was then diagnosed with humidifier lung based on the bronchoscopy and provocative testing findings. Hence, ultrasonic humidifier lung should be considered as a differential diagnosis in patients presenting with the reversed halo sign, and a detailed medical history must be taken.
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Background: Humidifier lung (HL) is a hypersensitivity pneumonitis resulting from exposure to humidifiers, with fungi from the humidifier as one of the etiologic agents. However, identification of the fungal species responsible for each case can be challenging because of difficulties in culturing fungi, their accurate identification, and interpreting the results of specific serum IgG testing. Objective: To clarify the best way to determine the causative fungal species of each HL case. Methods: We report 2 cases with HL in which rare fungi were identified as causative agents. In addition, we searched MEDLINE for previous publications on HL caused by fungi and performed a literature review focusing on clinical testing for the determination of causal fungal species. Results: In our 2 cases, we identified Fusarium oxysporum species complex, Purpureocillium lilacinum, Acremonium sclerotigenum/egyptiacum as the causative fungal species, based on findings that these could be cultured from humidifier water (HW) and precipitins against these fungi were also positive. The literature review identified 31 HL cases in which the causative fungal species had been documented. In more than half of the cases (17 of 31) there was a concordance between the fungal species cultured from HW and the presence of specific IgG in the blood. Conclusion: We recommend performing culture of fungi from HW and specific serum IgG testing for the accurate determination of the causative fungal species in HL, and concordance between them serves as a rationale for the determination of causative fungal species.
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Asthma therapy in general has improved a lot in recent years, but it is still a major problem that severe asthma, which accounts for 10 to 20%, still suffers from strong symptoms on a daily basis despite all therapeutic agents used in combination. American SARP and European ENFUMOSA started in 2000 to advance pathophysiological insights of severe asthma. Clinical usage of antibodies and inhibitors against IgE, TNF, IL-5, IL-4, IL-13, and TSLP are also accumulating. Some of these molecular-targeted drugs improve respiratory function and reduce acute exacerbations in patients with severe asthma. Until now, cytokines have been assumed to be involved in chronic inflammation, but it is also interesting to elucidate the pathways of how cytokines are involved in respiratory function and acute exacerbations. We registered approximately 100 steroid-dependent asthma patients in Japan. Although long-lasting poor control of the disease was considered the cause of severe asthma in the past, steroid dependence in one third of the cases occurred within 2-3 years after the onset. Steroid resistance seems a key process from the early stage of the disease. Steroid resistance of T cell level was induced by extracellular co-stimulation and cytokine signals. The inhibition may improve steroid sensitivity and treat steroid-resistant asthma. Therefore, we established a steroid-resistant asthma model for the first time by transferring steroid resistant T cell clones, and analyzed the steroid sensitivity recovery effect of CTLA4-Ig. In addition, a multicenter, double-blind, placebo-controlled exploratory trial was performed as a POC study investigating the efficacy of abatacept in treatment-resistant severe asthma. Elucidation of the pathophysiology and mechanism by which steroids do not work is expected to be a breakthrough for the prevention and treatment of severe asthma.
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Asma , Citocinas , Método Duplo-Cego , Humanos , Japão , Esteroides/uso terapêuticoRESUMO
We herein present a case of a 71-year-old woman with primary Sjogren's syndrome (SjS), who developed bilateral pleural effusion and ground glass opacity during treatment with low-dose prednisolone. The pleural effusion and bronchoalveolar lavage fluid revealed elevation of lymphocytes. Thoracoscopic pleural biopsy showed infiltration of lymphocytes with no evidence of other diseases, confirming SjS-related pleuritis. Therefore, we initiated 20 mg prednisolone and pleural effusion was rapidly resolved. Our results indicate that SjS can be rarely complicated with pleuritis. In addition, thoracoscopic pleural biopsy and a rapid response to steroid treatment would be helpful for diagnosing SjS-related pleuritis.
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It has been reported that tuberculosis (TB) worsens after cessation of tumor necrosis factor-α inhibitors and starting anti-TB treatment. Little is known about the immunological pathogenesis of this paradoxical response (PR). We report the first case of a TB patient in whom PR occurred concurrently with elevation of circulating tumor necrosis factor-α (TNFα) levels. A 75-year-old woman, who had been treated with adalimumab for SAPHO syndrome, developed disseminated TB. Soon after administration of anti-TB treatment (isoniazid, rifampicin, pyrazinamide, and ethambutol), and after discontinuation of adalimumab, a PR occurred. Serial testing of serum cytokine levels revealed a marked increase in TNFα, and a decline in interferon-γ levels. Despite intensive treatment with antibiotics, prednisolone, noradrenaline, and mechanical ventilation, acute respiratory distress syndrome developed and she died. Thus, overproduction of TNFα after cessation of TNFα inhibitors may partially account for the pathogenesis of a PR. This supports preventative or therapeutic reinitiation of TNFα inhibitors when PR occurs. Serial monitoring of circulating inflammatory cytokine levels could lead to earlier identification of a PR.
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Thyroid metastases from lung cancer are very rare. A woman aged 42â years with a tumour in the lower lobe of the right lung was diagnosed as having lung adenocarcinoma positive for echinoderm microtubule-associated proteinlike 4-anaplastic lymphoma kinase. Positron emission tomography demonstrated fluorodeoxyglucose accumulation in the lower lobe of the right lung, the right thyroid lobe and both adrenal glands. We performed fine-needle aspiration biopsy (FNAB) and used reverse transcriptase-PCR (RT-PCR) to diagnose the patient as having metastatic lung adenocarcinoma to the thyroid gland. We believe that FNAB combined with RT-PCR can be an effective method for diagnosing metastatic lung adenocarcinoma to the thyroid gland.
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Adenocarcinoma/patologia , Adenocarcinoma/secundário , Neoplasias Pulmonares/patologia , Neoplasias da Glândula Tireoide/secundário , Adenocarcinoma/diagnóstico , Adulto , Biópsia por Agulha Fina , Feminino , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias da Glândula Tireoide/diagnósticoRESUMO
RATIONALE: The etiology and outcome of diffuse acute infectious bronchiolitis (DAIB) in adults is not well known. OBJECTIVES: To retrospectively review adult patients with DAIB without pneumonia, document the etiologies and outcomes, and assess the relation between DAIB and postinfectious bronchiolitis obliterans. METHODS: We retrospectively analyzed medical records of 1,664 patients with lower respiratory tract infections admitted to our institution in Saitama, Japan. DAIB was diagnosed when patients developed acute feverish lower respiratory tract infection and chest computed tomography demonstrated mainly multiple centrilobular nodules in four or more lobes. Pneumonia was diagnosed when patients developed acute feverish lower respiratory tract infection and chest computed tomography demonstrated consolidation and/or ground-glass opacities with or without centrilobular nodules. MEASUREMENTS AND MAIN RESULTS: Of the 1,664 patients, 20 (1.2%) and 1,644 (98.8%) patients were diagnosed as having DAIB and pneumonia, respectively. Of the 20 patients with DAIB, the etiology was determined in 16 (80%): 13 (65.0%) had a single pathogen and 3 (15.0%) had two pathogens. Detected organisms included Mycoplasma pneumoniae in eight (40.0%) patients, influenza virus in two (10.0%), influenza virus and Streptococcus pneumoniae in two (10.0%), Haemophilus influenzae in three (15.0%), and respiratory syncytial virus and rhinovirus in one (5.0%) patient. All patients improved and none developed postinfectious bronchiolitis obliterans. CONCLUSIONS: The three most common etiologies of DAIB in the studied adults were M. pneumoniae, influenza virus, and H. influenzae. None of the patients with DAIB developed postinfectious bronchiolitis obliterans.