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1.
BMC Pulm Med ; 24(1): 442, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39256717

RESUMEN

BACKGROUND: Amikacin  liposome inhalation suspension (ALIS) improved sputum culture conversion rate at 6 months for patients with refractory Mycobacterium avium complex pulmonary disease (MAC-PD) in an international phase 3 trial. Patient characteristics and chest high-resolution CT (HRCT) findings associated with ALIS effectiveness are poorly documented. OBJECTIVE: We aimed to clarify ALIS effectiveness for refractory MAC-PD at 6 months, elucidating associated patient characteristics and chest CT findings. METHODS: We reviewed medical records of 12 patients with refractory MAC-PD for whom ALIS treatment was initiated at Toho University Omori Medical Center from November 2021 through September 2022. All patients demonstrated treatment persistence for at least 3 months. They were divided into culture conversion and non-conversion groups using sputum culture conversion status after 6-month ALIS treatment initiation. Clinical and radiological characteristics were compared. RESULTS: Seven of the 12 patients (58.3%) achieved sputum culture conversion within 6 months. The culture conversion group had shorter pre-ALIS initiation treatment duration [21 months (16-25) vs. 62 months (32-69); p = 0.045]; lower cavitary lesion incidence on HRCT (28.6% vs. 100%; p = 0.028); and fewer clarithromycin (CLA)-resistant strains [0/7 (0%) vs. 3/5 (60%); p = 0.045]. Chest HRCT findings improved in 4 of 7 (57.1%) and 1 of 5 (20%) patients in the culture conversion and non-conversion groups, respectively. CONCLUSION: ALIS facilitated sputum culture conversion within 6 months in 58.3% of patients with refractory MAC-PD. Sputum culture conversion was significantly more frequent for CLA-susceptible strains and patients with fewer cavitary lesions. Improved CT findings after ALIS did not always correspond to sputum culture conversion.


Asunto(s)
Amicacina , Antibacterianos , Liposomas , Complejo Mycobacterium avium , Infección por Mycobacterium avium-intracellulare , Esputo , Tomografía Computarizada por Rayos X , Humanos , Amicacina/administración & dosificación , Masculino , Femenino , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Anciano , Administración por Inhalación , Persona de Mediana Edad , Antibacterianos/administración & dosificación , Esputo/microbiología , Estudios Retrospectivos , Resultado del Tratamiento , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/microbiología , Anciano de 80 o más Años , Suspensiones
2.
Surg Today ; 54(2): 122-129, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37278878

RESUMEN

PURPOSE: To establish accurate diagnostic criteria and predictors of treatment response for postoperative acute exacerbation (AE) in patients with lung cancer and idiopathic interstitial pneumonia (IIP). METHODS: Among 93 patients with IIP who underwent surgery for lung cancer, suspected postoperative AE developed in 20 (21.5%). Patients were divided into a progressive AE group, comprising patients with bilateral alveolar opacities and decreasing PaO2 ≥ 10 mmHg (n = 5); an incipient AE group, comprising patients with unilateral alveolar opacities and decreasing PaO2 ≥ 10 mmHg (n = 10); and an indeterminate AE group, comprising patients with alveolar opacities but decreasing PaO2 < 10 mmHg (n = 5). RESULTS: The progressive AE group had significantly higher 90-day mortality (80%) than the incipient AE group (10%, P = 0.017) or the indeterminate AE group (0%, P = 0.048). Bilateral opacities may indicate advanced AE and poor prognosis, whereas unilateral opacities may indicate an early stage of AE and a good prognosis. PaO2 < 10 mmHg may indicate conditions other than AE. CONCLUSIONS: In patients with lung cancer and IIP, decreasing PaO2 and HRCT findings may allow for the initiation of rapid and accurate treatment strategies for postoperative AE.


Asunto(s)
Neumonías Intersticiales Idiopáticas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/cirugía , Oxígeno , Presión Parcial , Estudios Retrospectivos , Neumonías Intersticiales Idiopáticas/diagnóstico por imagen , Pronóstico , Progresión de la Enfermedad
3.
BMC Pulm Med ; 23(1): 29, 2023 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-36658536

RESUMEN

BACKGROUND: In Mycobacterium avium complex pulmonary disease (MAC-PD), diagnosis requires a positive culture from at least two separate expectorated sputum specimens. The optimal number of sputum examinations remains unclear. OBJECTIVE: This study sought to elucidate the diagnostic yield of acid-fast bacilli in MAC-PD using 3 sputum specimens and to clarify the clinical characteristics of patients with MAC-PD diagnosed using 3 sputum specimens. Furthermore, we investigated the correlation between increased number of sputum specimens and diagnostic yield. METHODS: We reviewed the medical records of 139 patients with MAC-PD diagnosed at Toho University Omori Medical Center for whom at least three sputum specimens were examined before treatment from November 2014 through June 2021. Patients were classified into the 3-sputum diagnosed and the non-3 sputum diagnosed groups based on diagnostic procedure; clinical and radiological characteristics were compared. We also assessed diagnostic yield with the increased number of sputum specimens. RESULTS: Diagnostic yield with 3 sputum specimens was 16.5% (23/139). The 3-sputum diagnosed group had a lower body mass index [18.6(17-19.5) vs. 19.5(18-21.5); p = 0.014], and higher chest CT score [9(6.5-13) vs. 6(4-9); p = 0.011] including cavitary lesions (39.1% vs. 19%; p = 0.037) compared with the non-3 sputum diagnosed group. When the number of sputum specimens was increased to 6, the diagnostic yield increased to 23.7% (33/139). CONCLUSION: Diagnostic yield with 3 sputum specimens was 16.5%. Patients diagnosed using 3 sputum specimens had more severe chest CT findings including cavitary lesions. Increasing the number of sputum specimens to 6 improved diagnostic yield by 7.2%.


Asunto(s)
Enfermedades Pulmonares , Infección por Mycobacterium avium-intracellulare , Humanos , Complejo Mycobacterium avium , Infección por Mycobacterium avium-intracellulare/diagnóstico , Infección por Mycobacterium avium-intracellulare/microbiología , Esputo/microbiología , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/microbiología , Tomografía Computarizada por Rayos X
4.
Development ; 146(21)2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31676552

RESUMEN

During cochlear development, hair cells (HCs) and supporting cells differentiate in the prosensory domain to form the organ of Corti, but how one row of inner HCs (IHCs) and three rows of outer HCs (OHCs) are organized is not well understood. Here, we investigated the process of HC induction by monitoring Atoh1 expression in cochlear explants of Atoh1-EGFP knock-in mouse embryos and showed that only the cells that express Atoh1 over a certain threshold are selected for HC fate determination. HC induction initially occurs at the medial edge of the prosensory domain to form IHCs and subsequently at the lateral edge to form OHCs, while Hedgehog signaling maintains a space between IHCs and OHCs, leading to formation of the tunnel of Corti. These results reveal dynamic Atoh1 expression in HC fate control and suggest that multi-directional signals regulate OHC induction, thereby organizing the prototype of the organ of Corti.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/fisiología , Cóclea/embriología , Células Ciliadas Auditivas/citología , Animales , Tipificación del Cuerpo , Proteína Morfogenética Ósea 4/fisiología , Diferenciación Celular , Linaje de la Célula , Regulación del Desarrollo de la Expresión Génica , Proteínas Fluorescentes Verdes/fisiología , Proteínas Hedgehog/fisiología , Imagenología Tridimensional , Ratones , Microscopía Fluorescente , Microscopía por Video , Órgano Espiral/embriología , Receptores Notch/fisiología , Transducción de Señal
5.
BMC Pulm Med ; 22(1): 157, 2022 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-35468795

RESUMEN

BACKGROUND: The impact of co-infection with other pathogenic microorganisms after initiation of treatment for Mycobacterium avium complex pulmonary disease (MAC-PD) has not been clearly described. This study sought to clarify the clinical outcomes of co-infection with MAC after antimycobacterial therapy for MAC. METHODS: Co-infection status was defined as the detection of pathogenic microorganisms other than MAC in at least two consecutive sputum cultures 6-24 months after initiation of treatment. Chest computed tomography (CT) findings and culture results were compared between co-infection and MAC alone groups. RESULTS: The co-infection and MAC alone groups comprised 12 and 36 patients, respectively. The proportion of patients with sputum culture positive for MAC after 24 months of therapy did not differ significantly between the two groups [25% (3/12) vs. 16.7% (6/36); p = 0.671]. The proportion of patients with improved chest CT score after 24 months of starting treatment compared to baseline was significantly lower for the co-infection group than for the MAC alone group [16.7% (2/12) vs. 79.4% (27/34); p < 0.001]. In the co-infection group, median CT score values at 12 and 24 months did not differ from baseline. However, the MAC alone group showed significant improvement at 12 and 24 months compared with baseline. CONCLUSIONS: In the patient group with co-infection of other pathogenic microorganisms after treatment initiation for MAC there was no impact on therapeutic efficacy compared to the MAC alone group. However, therapeutic intervention interfered with improvement in chest CT findings such as nodule formation, bronchiectasis, infiltration, and cavitary lesions.


Asunto(s)
Bronquiectasia , Coinfección , Enfermedades Pulmonares , Infección por Mycobacterium avium-intracellulare , Bronquiectasia/diagnóstico , Coinfección/tratamiento farmacológico , Humanos , Enfermedades Pulmonares/diagnóstico , Complejo Mycobacterium avium , Infección por Mycobacterium avium-intracellulare/complicaciones , Infección por Mycobacterium avium-intracellulare/diagnóstico , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico
6.
Surg Today ; 52(5): 736-744, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34347162

RESUMEN

Postoperative exacerbation of interstitial pneumonia in patients with interstitial lung disease and lung cancer has emerged as a serious problem. Therefore, we need to determine the risk factors for the development of postoperative exacerbation of interstitial pneumonia in this population. There are several subtypes of interstitial lung disease, which may lead to confusion about the treatment of patients with interstitial lung disease and lung cancer. Among the idiopathic forms of interstitial lung disease, we focused on idiopathic pulmonary fibrosis (IPF) and reviewed the surgical treatments used for patients with IPF and lung cancer.


Asunto(s)
Fibrosis Pulmonar Idiopática , Enfermedades Pulmonares Intersticiales , Neoplasias Pulmonares , Humanos , Fibrosis Pulmonar Idiopática/complicaciones , Fibrosis Pulmonar Idiopática/cirugía , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/cirugía , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/cirugía , Periodo Posoperatorio , Factores de Riesgo
7.
Dev Biol ; 460(2): 164-175, 2020 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-31843520

RESUMEN

Inhibitor of differentiation and DNA-binding (Id) proteins, Id1 to Id4, function in the regulation of cellular proliferation and differentiation. Id proteins have been shown to interact with bHLH proteins and other proteins involved in regulating cellular proliferation and differentiation, suggesting a widespread regulatory function. Id1-3 are known to be expressed in the prosensory domain of developing cochlea. However, the roles of Id genes in cochlear development are not fully elucidated. The deficiency of any of the Id1-3 genes individually has little effect on the cochlear development, and therefore the functional redundancy among these genes have been presumed to explain the absence of phenotype. Here, we show that conditional knockout of Id1/2/3 genes (Id TKO) causes major defects in morphogenesis and cellular patterning in the development of mammalian cochlea. Id TKO cochlea was 82% shorter than control, and both decreased proliferation and increased cell death caused the hypomorph. Sox2-positive prosensory domain was formed in Id TKO cochlea, but the formation of the medial-lateral (central-peripheral) axis was disturbed; the boundary between the medial and lateral compartments in the prosensory domain was partially doubled; the number of inner hair cells per unit length increased, and the number of outer hair cells decreased. Furthermore, the lateral non-sensory compartment expressing Bmp4 and Lmo3 was missing. Thus, the patterning of the lateral epithelium was more affected than the medial epithelium. These results suggested that Id genes are crucial for morphogenesis of the cochlea duct and patterning of the lateral epithelium in the developing cochlea. Further analyses by quantitative RT-PCR and immunostaining using cochlear explants with a Bmp pathway inhibitor revealed that the Bmp-Id pathway originates from the lateral non-sensory compartment and promotes outer hair cell differentiation.


Asunto(s)
Cóclea/enzimología , Embrión de Mamíferos/embriología , Proteínas Inhibidoras de la Diferenciación/metabolismo , Organogénesis/fisiología , Animales , Proteína Morfogenética Ósea 4/genética , Proteína Morfogenética Ósea 4/metabolismo , Cóclea/citología , Embrión de Mamíferos/citología , Proteínas Inhibidoras de la Diferenciación/genética , Ratones , Ratones Noqueados , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismo
8.
Eur Respir J ; 57(1)2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32703779

RESUMEN

BACKGROUND: A randomised controlled trial in Japan showed that inhaled N-acetylcysteine monotherapy stabilised serial decline in forced vital capacity (FVC) in some patients with early idiopathic pulmonary fibrosis (IPF). However, the efficacy and tolerability of combination therapy with an antifibrotic agent and inhaled N-acetylcysteine are unknown. METHODS: This 48-week, randomised, open-label, multicentre phase 3 trial compared the efficacy and tolerability of combination therapy with pirfenidone plus inhaled N-acetylcysteine 352.4 mg twice daily with the results for pirfenidone alone in patients with IPF. The primary end-point was annual rate of decline in FVC. Exploratory efficacy measurements included serial change in diffusing capacity of the lung for carbon monoxide (D LCO) and 6-min walk distance (6MWD), progression-free survival (PFS), incidence of acute exacerbation, and tolerability. RESULTS: 81 patients were randomly assigned in a 1:1 ratio to receive pirfenidone plus inhaled N-acetylcysteine (n=41) or pirfenidone (n=40). The 48-week rate of change in FVC was -300 mL and -123 mL, respectively (difference -178 mL, 95% CI -324--31 mL; p=0.018). Serial change in D LCO, 6MWD, PFS and incidence of acute exacerbation did not significantly differ between the two groups. The incidence of adverse events (n=19 (55.9%) for pirfenidone plus N-acetylcysteine; n=18 (50%) for pirfenidone alone) was similar between groups. CONCLUSIONS: Combination treatment with inhaled N-acetylcysteine and pirfenidone is likely to result in worse outcomes for IPF.


Asunto(s)
Acetilcisteína , Fibrosis Pulmonar Idiopática , Acetilcisteína/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Humanos , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Japón , Piridonas/uso terapéutico , Resultado del Tratamiento , Capacidad Vital
9.
Respiration ; 100(9): 877-885, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34044411

RESUMEN

BACKGROUND: The optimal bronchoscopy procedure for diagnosis of pulmonary nontuberculous mycobacteria (NTM) infection is unclear. OBJECTIVE: This study investigated the usefulness of bronchial brushing in bronchoscopy for diagnosis of pulmonary NTM infection in patients with suspected NTM lung disease and nodular bronchiectasis on chest computed tomography (CT) images. METHODS: Bronchoscopy was prospectively performed for 69 patients with clinically suspected pulmonary NTM infection on chest CT from December 2017 through December 2019. Before and after bronchial brushing, bronchial washing was performed with 20 or 40 mL of normal sterile saline at the same segmental or subsegmental bronchi. Before and after bronchial brushing, samples of the washing fluid (pre- and postbrushing samples) and brush deposits (brush samples) were obtained and cultured separately. RESULTS: NTM was detected in 37 of the 69 (53.6%) patients (Mycobacterium avium in 27, Mycobacterium intracellulare in 7, M. abscessus in 2, and M. kansasii in 2). NTM was detected in 34 (49.3%) prebrushing samples, in 27 (39.1%) postbrushing samples, and in 20 (29.0%) brush samples from the 69 patients. In 2 (2.9%) patients, NTM was detected only in postbrushing samples; in 1 (1.4%) patient, NTM was detected only in a brush sample. As compared with bronchial washing only, additional bronchial brushing increased the NTM culture-positive rate by 4.3% (3/69). Bronchial brushing caused bleeding, requiring hemostasis in 5 (7.2%) patients. CONCLUSION: Additional bronchial brushing increased the NTM culture-positive rate by only 4.3% (3/69), as compared with bronchial washing alone. Thus, the usefulness of brushing appears to be limited.


Asunto(s)
Bronquiectasia , Infecciones por Mycobacterium no Tuberculosas , Broncoscopía , Humanos , Pulmón , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Complejo Mycobacterium avium , Micobacterias no Tuberculosas
10.
Am J Respir Crit Care Med ; 201(9): 1110-1119, 2020 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-31917621

RESUMEN

Rationale: Acute exacerbation during the course of idiopathic pulmonary fibrosis causes a poor prognosis. Coagulation abnormalities and endothelial damage are involved in its pathogenesis. Thrombomodulin alfa, a recombinant human soluble thrombomodulin, has anticoagulant and antiinflammatory effects. Several clinical studies have shown that thrombomodulin alfa may improve survival of acute exacerbation.Objectives: To determine the efficacy and safety of thrombomodulin alfa compared with placebo in acute exacerbation of idiopathic pulmonary fibrosis.Methods: This randomized, double-blind placebo-controlled phase 3 study conducted at 27 sites in Japan involved patients with an acute exacerbation of idiopathic pulmonary fibrosis. Subjects were randomized 1:1 to receive placebo or thrombomodulin alfa (380 U/kg/d for 14 d by intravenous drip infusion). All subjects were treated with high-dose corticosteroid therapy. The primary endpoint was the survival proportion on Day 90.Measurements and Main Results: Of the 82 randomized subjects, 77 completed the study and were included in the full analysis set (thrombomodulin alfa, n = 40; placebo, n = 37). The survival proportions on Day 90 were 72.5% (29 of 40) in the thrombomodulin alfa group and 89.2% (33 of 37) in the placebo group, a difference of -16.7 percentage points (95% confidence interval, -33.8 to 0.4%; P = 0.0863). In the safety population (n = 80), bleeding adverse events occurred in the thrombomodulin alfa group (10 of 42; 23.8%) and the placebo group (4 of 38; 10.5%).Conclusions: Thrombomodulin alfa did not improve the 90-day survival proportion. The present results suggest that the use of thrombomodulin alfa for the treatment of acute exacerbation of idiopathic pulmonary fibrosis not be recommended.Clinical trial registered with www.clinicaltrials.gov (NCT02739165).


Asunto(s)
Anticoagulantes/uso terapéutico , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Proteínas Recombinantes/uso terapéutico , Trombomodulina/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Femenino , Humanos , Fibrosis Pulmonar Idiopática/epidemiología , Infusiones Intravenosas , Japón/epidemiología , Masculino , Persona de Mediana Edad , Efecto Placebo , Brote de los Síntomas
11.
BMC Pulm Med ; 21(1): 174, 2021 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-34020622

RESUMEN

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an important risk factor for postoperative complications and mortality. To determine the effects of perioperative combination therapy, using a long-acting muscarinic antagonist (LAMA) and a long-acting ß2 agonist (LABA), on preoperative lung function, postoperative morbidity and mortality, and long-term outcome in COPD patients. METHODS: Between January 2005 and October 2019, 130 consecutive patients with newly diagnosed COPD underwent surgery for lung cancer. We conducted a retrospective review of their medical record to evaluate that LAMA/LABA might be an optimal regimen for patients with COPD undergoing surgery for lung cancer. All patients were received perioperative rehabilitation and divided into 3 groups according to the type of perioperative inhaled therapy and management: LAMA/LABA (n = 64), LAMA (n = 23) and rehabilitation only (no bronchodilator) (n = 43). We conducted a retrospective review of their medical records. RESULTS: Patients who received preoperative LAMA/LABA therapy showed significant improvement in lung function before surgery (p < 0.001 for both forced expiratory volume in 1 s (FEV1) and percentage of predicted forced expiratory volume in 1 s (FEV1%pred). Compared with patients who received preoperative LAMA therapy, patients with LAMA/LABA therapy had significantly improved lung function (ΔFEV1, LAMA/LABA 223.1 mL vs. LAMA 130.0 mL, ΔFEV1%pred, LAMA/LABA 10.8% vs. LAMA 6.8%; both p < 0.05). Postoperative complications were lower frequent in the LAMA/LABA group than in the LAMA group (p = 0.007). In patients with moderate to severe air flow limitation (n = 61), those who received LAMA/LABA therapy had significantly longer overall survival and disease-free survival compared with the LAMA (p = 0.049, p = 0.026) and rehabilitation-only groups (p = 0.001, p < 0.001). Perioperative LAMA/LABA therapy was also associated with lower recurrence rates (vs. LAMA p = 0.006, vs. rehabilitation-only p = 0.008). CONCLUSIONS: We believe this treatment combination is optimal for patients with lung cancer and COPD.


Asunto(s)
Adenocarcinoma/complicaciones , Agonistas de Receptores Adrenérgicos beta 2/uso terapéutico , Neoplasias Pulmonares/complicaciones , Antagonistas Muscarínicos/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Adenocarcinoma/cirugía , Administración por Inhalación , Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Anciano , Anciano de 80 o más Años , Manejo de la Enfermedad , Quimioterapia Combinada , Femenino , Volumen Espiratorio Forzado , Humanos , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Antagonistas Muscarínicos/administración & dosificación , Neumonectomía , Pronóstico , Modelos de Riesgos Proporcionales , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Estudios Retrospectivos
12.
AJR Am J Roentgenol ; 213(1): 104-114, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30973774

RESUMEN

OBJECTIVE. The lung is one of the organs possibly involved in microscopic polyangiitis (MPA), and myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA) is commonly found in patients with MPA. The aim of this study was to assess pulmonary lesions in Japanese patients with MPA. SUBJECTS AND METHODS. This prospective study was based on 144 patients with MPA who were enrolled in the Remission Induction Therapy in Japanese Patients With ANCA-Associated Vasculitis and Rapidly Progressive Glomerulonephritis Study and who underwent chest high-resolution CT (HRCT) imaging at the time of diagnosis during 2011-2014. We reviewed the electronic case report forms of patients with MPA who did and did not have interstitial pneumonia (IP), and the clinical features and laboratory findings of these groups were compared. RESULTS. Abnormal HRCT findings were noted in 134 of the 144 patients (93%). Chest HRCT findings included ground-glass opacity (n = 72; 50%), reticulation (n = 69; 48%), traction bronchiectasis (n = 57; 42%), honeycombing (n = 44; 31%), and emphysema (n = 32; 22%). IP was diagnosed radiologically in 74 patients (51%), 38% of whom had the usual IP (UIP) pattern. Ground-glass opacity, reticulation, traction bronchiectasis, honeycombing, and interlobular septal thickening were frequent in patients with IP (p < 0.05). Patients with MPA with the UIP or possible UIP pattern also had minor findings, such as bronchial wall thickening, consolidation, increased attenuation around honeycombing, and traction bronchiectasis. CONCLUSION. IP (51%) was most commonly observed in Japanese patients with MPA, and 38% of these patients exhibited a UIP pattern. Increased attenuation around honeycombing or traction bronchiectasis was also found.

13.
Respiration ; 97(1): 52-59, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30149393

RESUMEN

BACKGROUND: Recent clinical trials demonstrated the benefits of several guided-bronchoscopy technologies for the diagnosis of peripheral pulmonary lesions (PPLs). However, introduction of these technologies is expensive. Therefore, in clinical practice, these are unavailable in many hospitals. In contrast, virtual bronchoscopy (VB) using the computed tomography (CT) workstation can be made available immediately without additional cost as many hospitals already have the CT scan facility. However, the effectiveness of VB alone remains to be shown. OBJECTIVES: The aim of this study was to investigate the effect of VB using the CT workstation in hospitals performing conventional bronchoscopy. METHODS: Results from consecutive patients who underwent bronchoscopy for small PPLs (major diameter ≤30 mm) were retrospectively reviewed. Sixty-nine patients who underwent bronchoscopy without VB from April 2014 to March 2015 and 56 patients who underwent bronchoscopy with VB from April 2015 to December 2015 were assigned to non-VB and VB groups, respectively. We compared the two groups and analyzed the factors affecting the diagnostic yield. RESULTS: The VB group had a significantly higher diagnostic yield than the non-VB group (57.1 vs. 33.3%; p = 0.008). In the multivariate analysis, VB was identified as a significant factor affecting the diagnostic yield (odds ratio: 3.30, p = 0.011). CONCLUSIONS: In the conventional bronchoscopy settings, VB using the CT workstation is efficient for the diagnosis of PPLs when other guided-bronchoscopy techniques are unavailable.


Asunto(s)
Broncoscopía/estadística & datos numéricos , Imagenología Tridimensional , Neoplasias Pulmonares/diagnóstico , Pulmón/diagnóstico por imagen , Tomografía Computarizada Multidetector/instrumentación , Realidad Virtual , Adulto , Anciano , Anciano de 80 o más Años , Broncoscopía/métodos , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos
14.
J Infect Chemother ; 25(12): 936-942, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31186197

RESUMEN

BACKGROUND: For patients with non-human immunodeficiency virus (HIV) Pneumocystis pneumonia (PCP), data are limited on serial changes in serum biomarkers and the correlations with clinical outcomes. OBJECTIVE: This study evaluated serial change in serum biomarkers and clinical outcomes of non-HIV PCP. METHODS: We retrospectively reviewed data from 63 patients treated for non-HIV PCP at Toho University Omori Medical Center. The patients were classified as survivors and nonsurvivors on the basis of 60-day PCP mortality. The groups were compared for clinical course and levels of serum biomarkers (ß-D glucan, Krebs von den Lungen-6 antigen [KL-6], and surfactant protein-D [SP-D]), which were measured at baseline, and 7 days and 14 days after starting treatment. In addition, serial changes in serum biomarkers were analyzed in survivors and nonsurvivors. RESULTS: There were 14 PCP nonsurvivors and 49 survivors. Biomarker values were not different between groups at baseline. At 7 and 14 days after starting treatment, the proportions of patients with elevated ß-D glucan and KL-6 did not significantly differ between groups; however, the proportion of patients with elevated SP-D was significantly lower among survivors than among nonsurvivors (57.1% vs. 100%, p = 0.009; 30% vs. 100%, p < 0.001; respectively). SP-D on day 14 was significantly lower than that at baseline among survivors (99.6 [61.0-190.3] vs. 156 [100.8-283.5]; p = 0.045) but significantly higher among nonsurvivors (974 [744.5-1565] vs. 317 [211-448]; p = 0.03). CONCLUSION: Serum SP-D value continues to increase after failure of treatment for non-HIV PCP and may thus be associated with outcomes for non-HIV PCP patients.


Asunto(s)
Antibacterianos/uso terapéutico , Huésped Inmunocomprometido , Pneumocystis carinii/aislamiento & purificación , Neumonía por Pneumocystis/terapia , Sobrevivientes/estadística & datos numéricos , Anciano , Biomarcadores/sangre , Terapia Combinada/métodos , Femenino , Glucocorticoides/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Mucina-1/sangre , Mucina-1/inmunología , Terapia por Inhalación de Oxígeno , Neumonía por Pneumocystis/sangre , Neumonía por Pneumocystis/microbiología , Neumonía por Pneumocystis/mortalidad , Proteína D Asociada a Surfactante Pulmonar/sangre , Proteína D Asociada a Surfactante Pulmonar/inmunología , Estudios Retrospectivos , Insuficiencia del Tratamiento , Combinación Trimetoprim y Sulfametoxazol , beta-Glucanos/sangre , beta-Glucanos/inmunología
15.
Medicina (Kaunas) ; 55(5)2019 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-31137593

RESUMEN

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an acute respiratory worsening of unidentifiable cause that sometimes develops during the clinical course of IPF. Although the incidence of AE-IPF is not high, prognosis is poor. The pathogenesis of AE-IPF is not well understood; however, evidence suggests that coagulation abnormalities and inflammation are involved. Thrombomodulin is a transmembranous glycoprotein found on the cell surface of vascular endothelial cells. Thrombomodulin combines with thrombin, regulates coagulation/fibrinolysis balance, and has a pivotal role in suppressing excess inflammation through its inhibition of high-mobility group box 1 protein and the complement system. Thus, thrombomodulin might be effective in the treatment of AE-IPF, and we and other groups found that recombinant human soluble thrombomodulin improved survival in patients with AE-IPF. This review summarizes the existing evidence and considers the therapeutic role of thrombomodulin in AE-IPF.


Asunto(s)
Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Trombomodulina/uso terapéutico , Biomarcadores/análisis , Biomarcadores/sangre , Progresión de la Enfermedad , Proteína HMGB1/análisis , Proteína HMGB1/sangre , Humanos , Fibrosis Pulmonar Idiopática/fisiopatología , Pronóstico , Resultado del Tratamiento
16.
J Infect Chemother ; 24(10): 822-827, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30054229

RESUMEN

BACKGROUND: We occasionally treat patients with clinically suspected pulmonary Mycobacterium avium complex (MAC) infection and negative MAC culture on bronchoscopy. OBJECTIVE: This study aimed to investigate the usefulness of bronchoscopy in patients with suspected MAC lung disease with nodular bronchiectasis on chest computed tomography (CT) and to clarify the clinical characteristics of these patients. METHODS: We reviewed the records of 71 patients with clinically suspected pulmonary MAC infection on chest CT who underwent bronchoscopy. The patients were classified on the basis of MAC culture result, and their clinical characteristics were compared. RESULTS: MAC was detected in 33 of the 71 (46.5%) patients (positive group), and 35 (49.3%) were culture-negative for nontuberculous mycobacteria (NTM) (negative group). NTM other than MAC were detected in 3 of 71 (4.2%) patients. MAC was not detected in 14 of 38 (36.8%) patients positive for GPL core IgA antibody. Patients in the positive group had a higher body mass index (20.1 ± 3.4 vs 18.5 ± 2.9 kg/m2; p = 0.047) and positive rate for GPL core IgA antibody (72.7% vs 40%; p = 0.006) and a lower chronic obstructive pulmonary disease assessment test score (6.6 ± 6.6 vs 11.7 ± 8.5; p = 0.016) and rate of positive culture for Pseudomonas aeruginosa or Haemophilus influenzae (12.1% vs 45.7%; p = 0.003), as compared with the negative group. CONCLUSION: Bronchoscopy is useful for diagnosis of MAC in patients who cannot be diagnosed by sputum examination. In addition, patients with pulmonary MAC disease had less severe subjective symptoms and weight loss than did those with a negative MAC culture on bronchoscopy.


Asunto(s)
Bronquiectasia/diagnóstico , Broncoscopía , Enfermedades Pulmonares/diagnóstico , Complejo Mycobacterium avium/inmunología , Infección por Mycobacterium avium-intracellulare/diagnóstico , Anciano , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Índice de Masa Corporal , Bronquiectasia/sangre , Estudios de Cohortes , Femenino , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Pulmón/patología , Enfermedades Pulmonares/sangre , Masculino , Persona de Mediana Edad , Infección por Mycobacterium avium-intracellulare/sangre , Estudios Retrospectivos
17.
J Clin Microbiol ; 55(6): 1738-1746, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28330887

RESUMEN

We evaluated the usefulness of an Aspergillus galactomannan (GM) test, a ß-d-glucan (ßDG) test, and two different Aspergillus PCR assays of bronchoalveolar lavage fluid (BALF) samples for the diagnosis of chronic pulmonary aspergillosis (CPA). BALF samples from 30 patients with and 120 patients without CPA were collected. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for each test individually and in combination with other tests. The optical density index values, as determined by receiver operating characteristic analysis, for the diagnosis of CPA were 0.5 and 100 for GM and ßDG testing of BALF, respectively. The sensitivity and specificity of the GM test, ßDG test, and PCR assays 1 and 2 were 77.8% and 90.0%, 77.8% and 72.5%, 86.7% and 84.2%, and 66.7% and 94.2%, respectively. A comparison of the PCR assays showed that PCR assay 1 had a better sensitivity, a better negative predictive value, and a better negative likelihood ratio and PCR assay 2 had a better specificity, a better positive predictive value, and a better positive likelihood ratio. The combination of the GM and ßDG tests had the highest diagnostic odds ratio. The combination of the GM and ßDG tests on BALF was more useful than any single test for diagnosing CPA.


Asunto(s)
Aspergillus/aislamiento & purificación , Líquido del Lavado Bronquioalveolar/microbiología , Pruebas Diagnósticas de Rutina/métodos , Inmunoensayo/métodos , Mananos/análisis , Reacción en Cadena de la Polimerasa/métodos , Aspergilosis Pulmonar/diagnóstico , beta-Glucanos/análisis , Anciano , Anciano de 80 o más Años , Aspergillus/química , Aspergillus/genética , Femenino , Galactosa/análogos & derivados , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Proteoglicanos , Sensibilidad y Especificidad
18.
Allergol Int ; 66(3): 411-417, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27712949

RESUMEN

BACKGROUND: Maintaining high treatment adherence levels is critical for effective management of chronic diseases. The Adherence Starts with Knowledge 20 (ASK-20) questionnaire is the only linguistically validated patient-reported treatment adherence tool available in Japan. We conducted additional analyses on ASK-20 data from Japanese adults with asthma. METHODS: This was a prospective, non-interventional, single-visit, multi-centre study in Japanese adults (n = 300) with asthma receiving long-term treatment with inhaled corticosteroids (ICS) or ICS/long-acting beta-agonists. We tested the reliability, validity and the relationship between different adherence conditions and ASK-20 score. At one centre, ICS adherence prescription rate was calculated retrospectively based on 2-year percentage ICS adherence data contained within medical records. RESULTS: The ASK-20 had good internal consistency reliability (Cronbach's alpha = 0.76; n = 290). Discriminant validity was demonstrated with significant correlations between the percentage ICS adherence rates and both the mean ASK-20 total score and mean total barrier count (TBC) (r = -0.51 and -0.58, p < 0.001; n = 111). The ASK-20 total score discriminated between subjects with good and poor adherence measured by patients' reported questionnaire and between those of high and low percentage ICS adherence rates. All other factors that possibly affect adherence were correlated with the mean ASK-20 total score and mean TBC in addition to the number of medicines taken every day. CONCLUSIONS: The Japanese ASK-20 is a reliable tool for assessing possible medication adherence barriers and adherence behaviour in Japanese adults with asthma. Furthermore, our results are comparable with those obtained using the ASK-20 in the United States.


Asunto(s)
Corticoesteroides/administración & dosificación , Antiasmáticos/administración & dosificación , Asma/tratamiento farmacológico , Asma/epidemiología , Administración por Inhalación , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Asma/diagnóstico , Quimioterapia Combinada , Femenino , Encuestas de Atención de la Salud , Humanos , Japón/epidemiología , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Reproducibilidad de los Resultados , Resultado del Tratamiento , Adulto Joven
19.
Respirology ; 20(3): 445-52, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25639750

RESUMEN

BACKGROUND AND OBJECTIVE: Treatment with pirfenidone may slow the decline in vital capacity and increase progression-free survival (PFS) in idiopathic pulmonary fibrosis (IPF). The effects of combination therapy with inhaled N-acetylcysteine (NAC) and pirfenidone are unclear. We assessed the effects of this combination therapy in patients with advanced IPF. METHODS: Patients with a diagnosis of advanced IPF (Japanese Respiratory Society stage III/IV IPF) and a relative decline in forced vital capacity (FVC) of ≥ 10% within the previous 6 (± 2) months were enrolled. Outcomes were evaluated in a 12-month follow-up pulmonary function test. Treatment was considered ineffective if the decline in FVC was ≥ 10% and effective if the decline was <10%. We compared clinical characteristics, effectiveness and PFS between patients receiving inhaled NAC plus pirfenidone (n = 24) and those receiving pirfenidone alone (control; n = 10). RESULTS: Data from 34 IPF patients (age range, 59-82 years) were analysed. At the 12-month follow-up examination, treatment was deemed effective in 8 of 17 (47%) patients receiving NAC plus pirfenidone and in 2 of 10 (20%) receiving pirfenidone alone. The annual rate of change in FVC was -610 mL in the NAC plus pirfenidone group and -1320 mL in the pirfenidone group (P < 0.01). PFS was longer (304 days) in the NAC plus pirfenidone group than in the pirfenidone group (168 days; P = 0.016). CONCLUSIONS: Combination treatment with inhaled NAC and oral pirfenidone reduced the rate of annual FVC decline and improved PFS in patients with advanced IPF.


Asunto(s)
Acetilcisteína/administración & dosificación , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Piridonas/administración & dosificación , Administración por Inhalación , Anciano , Anciano de 80 o más Años , Antiinflamatorios no Esteroideos/administración & dosificación , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Depuradores de Radicales Libres/administración & dosificación , Humanos , Fibrosis Pulmonar Idiopática/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Capacidad Vital/efectos de los fármacos
20.
Respiration ; 89(3): 201-7, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25659984

RESUMEN

BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) can be fatal, and abnormalities in the coagulation system of patients with AE-IPF have been reported. Recombinant human soluble thrombomodulin (rhTM) forms a complex with thrombin to inactivate coagulation. It also inhibits high-mobility group box protein 1 (HMGB-1), which results in the suppression of inflammation. OBJECTIVES: We aimed to evaluate the effectiveness of rhTM for the treatment of AE-IPF. METHODS: We retrospectively reviewed the medical records of 41 patients with AE-IPF who were admitted to our institution during the period 2006-2013. The clinical features and outcomes of 16 patients treated with rhTM (rhTM group) were compared with those of 25 patients treated with conventional therapy (control group). Patients were treated with corticosteroid (CS) pulse therapy for 3 days, followed by maintenance treatment with a tapered dose of CS. Patients in the rhTM group also received rhTM (0.06 mg/kg/day) for 6 days as an initial treatment, in combination with CS. RESULTS: Except for D-dimer level, there were no significant differences in the baseline characteristics of the 2 groups. When compared with the control group, the rhTM group had a significantly higher survival rate at 3 months (40 vs. 69%, p = 0.048). A univariate Cox proportional hazards regression model showed that the predictive factors for survival were lactate dehydrogenase level and rhTM treatment. Regarding adverse events, 1 patient in the rhTM group developed mild bleeding events. CONCLUSION: rhTM as an add-on to conventional treatment may improve survival in patients with AE-IPF.


Asunto(s)
Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Trombomodulina/administración & dosificación , Anciano , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Fibrosis Pulmonar Idiopática/mortalidad , Japón/epidemiología , Masculino , Proteínas Recombinantes/administración & dosificación , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Resultado del Tratamiento
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