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1.
Sci Rep ; 14(1): 4438, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38396118

RESUMO

Multidrug therapy for Mycobacterium avium complex pulmonary disease (MAC-PD) results in negative sputum cultures. However, the prognostic value of this treatment approach remains unclear. This study aimed to clarify whether multidrug therapy reduces the incidence of events related to MAC-PD and improves the mortality rate. Patients who met the diagnostic criteria for MAC-PD at our hospital between 2003 and 2019 were retrospectively evaluated using medical records. Events related to MAC-PD were defined as hospitalisation for haemoptysis or respiratory infection and the development of chronic respiratory failure. There were 90 and 108 patients in the multidrug and observation groups, respectively. The median observation period was 86 months. Intergroup differences in body mass index, proportion of patients with cavities, and erythrocyte sedimentation rate were not significant. However, the observation group was older with a higher mean age (multidrug group: 62 years, observation group: 69 years; P < 0.001) and had a higher proportion of male patients (multidrug group: 13/90 [14.4%], observation group: 35/108 [32.4%]; P < 0.01). Furthermore, intergroup differences in the incidence of events related to MAC-PD (multidrug group: 26.69/1000 person-years, observation group: 25.49/1000 person-years), MAC-PD-associated mortality rate (multidrug group: 12.13/1000 person-years, observation group: 12.74/1000 person-years), and total mortality (multidrug group: 24.26/1000 person-years, observation group: 29.50/1000 person-years) were not significant. Many patients relapse even after multidrug therapy, and our findings suggest that multidrug therapy has no effect in preventing the onset of respiratory events or prolonging life expectancy.


Assuntos
Pneumopatias , Infecção por Mycobacterium avium-intracellulare , Humanos , Masculino , Pessoa de Meia-Idade , Complexo Mycobacterium avium , Infecção por Mycobacterium avium-intracellulare/microbiologia , Estudos Retrospectivos , Quimioterapia Combinada , Hansenostáticos/farmacologia , Pneumopatias/microbiologia , Prognóstico
2.
Intern Med ; 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38171855

RESUMO

High-altitude pulmonary edema (HAPE) is a life-threatening, noncardiogenic pulmonary edema that occurs in unacclimatized individuals rapidly ascending to high altitudes above 2,500 m above sea level. Until the entity of HAPE was first identified in a case report published in Japan in 1966, the symptoms of severe dyspnea or coma occurring in climbers of the Japan Alps were incorrectly attributed to pneumonia or congestive heart failure. The Shinshu University Hospital serves as the central facility for rescuing and treating patients with HAPE in the region. Over the past 50 years, a series of studies have been conducted at Shinshu University to gain a better understanding of the characteristics of HAPE. This review summarizes the major achievements of these studies, including their clinical features, management, and pathogenesis of HAPE, particularly in the Japanese population.

3.
Respir Investig ; 61(6): 687-697, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37708634

RESUMO

BACKGROUND: This study aimed to establish reference equations for single-breath lung carbon monoxide diffusing capacity (DLCO), alveolar volume (VA), and transfer coefficient of the lungs for carbon monoxide (KCO, sometimes written as DLCO/VA) in the Japanese population. A generalised additive model for location size and shape (GAMLSS) was used to build each equation. METHODS: To collect pulmonary function data throughout a broad age range, we prospectively obtained pulmonary function data from healthy volunteers and retrospectively obtained data from patients with normal diffusing capacity aged 16-85 years. RESULTS: In total, 702 tests were conducted. The validation group z-scores, except for DLCO in males, showed substantial discrepancies between the Global Lung Initiative (GLI) baseline prediction equations and the present study's prediction equations, indicating the need for a new reference value prediction approach. The root mean square errors of the DLCO, VA, and KCO reference values obtained from the present study's prediction equations were lower than those derived from the GLI and previous linear regression equations. CONCLUSIONS: Reference values obtained in this study were more appropriate for our sample than those derived from the existing baseline prediction equations. This research's contribution is the development of a more precise prediction equation that can be used to establish a reference value range for pulmonary diffusing capacity. ETHICS AND DISSEMINATION: This research does not include any dissemination plan (publications, data deposition and curation).


Assuntos
Monóxido de Carbono , Capacidade de Difusão Pulmonar , Masculino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , População do Leste Asiático , Estudos Retrospectivos , Pulmão , Valores de Referência
4.
High Alt Med Biol ; 24(3): 186-192, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-30475063

RESUMO

Kinota, Fumiya, Yunden Droma, Nobumitsu Kobayashi, Toshimichi Horiuchi, Yoshiaki Kitaguchi, Masanori Yasuo, Masao Ota, and Masayuki Hanaoka. The contribution of genetic variants of the gene encoding peroxisome proliferator-activated receptor-alpha gene (PPARA) to high-altitude hypoxia adaptation in Sherpa highlanders. High Alt Med Biol. 24:186-192, 2023.-Sherpa highlanders, who play invaluable roles in the exploration of Mount Everest, have exceptional tolerance to hypobaric hypoxia. Sherpa people are well known to possess the traits determined by genetic background for high-altitude adaptation. The metabolic adaptation mechanism is one of the biological ways for Sherpa highlanders in protecting them from hypoxia stress at high altitude. Studies have suggested that the gene encoding PPARA is associated with metabolic adaptation in the Himalayan population of Tibetans. This study attempts to investigate the genetic variants of the PPARA in Sherpa highlanders and the association with high-altitude hypoxia adaptation. Seven single-nucleotide polymorphisms (SNPs; rs135547, rs5769178, rs881740, rs4253712, rs5766741, and rs5767700 in introns and rs1800234 in exon 6) in the PPARA were genotyped in 105 Sherpa highlanders who lived in the Khumbu region (3440 m above sea level) and 111 non-Sherpa lowlanders who resided in Kathmandu (1300 m) in Nepal. By means of analyses of genetic distances, genotype distributions, allele frequencies, linkage disequilibrium, and haplotype constructions of the seven SNPs in the Sherpa highlanders versus the non-Sherpa lowlanders, it was revealed that the frequencies of minor alleles of rs4253712, rs5766741, rs5767700, and rs1800234 SNPs, as well as the frequency of haplotype constructed by the minor alleles of rs5766741-rs5767700-rs1800234, were significantly overrepresented in the Sherpa highlanders in comparison with the non-Sherpa lowlanders. The results strongly suggest that the genetic variants of the PPARA are likely to contribute to the high-altitude adaptation in Sherpa highlanders.


Assuntos
Doença da Altitude , Humanos , Doença da Altitude/genética , Altitude , Receptores Ativados por Proliferador de Peroxissomo , Adaptação Fisiológica/genética , Hipóxia/genética
5.
PeerJ ; 10: e13893, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35996666

RESUMO

Background: Sherpa highlanders demonstrate extraordinary tolerance to hypoxia at high altitudes, which may be achieved by mechanisms promoting microcirculatory blood flow and capillary density at high altitudes for restoring oxygen supply to tissues. Vascular endothelial growth factors (VEGFs) are important signaling proteins involved in vasculogenesis and angiogenesis which are stimulated by hypoxia. We hypothesize that the VEGF-A, the major member of the VEGF family, and the gene encoding VEGF-A (VEGFA) play a part in the adaptation to high-altitude hypoxia in Sherpa highlanders. Methods: Fifty-one Sherpa highlanders in Namche Bazaar village at a high altitude of 3,440 meters (m) above sea level and 76 non-Sherpa lowlanders in Kathmandu city at 1,300 m in Nepal were recruited for the study. Venous blood was sampled to obtain plasma and extract DNA from each subject. The plasma VEGF-A concentrations were measured and five single-nucleotide polymorphisms (SNPs, rs699947, rs833061, rs1570360, rs2010963, and rs3025039) in the VEGFA were genotyped. The VEGF-A levels and allelic frequencies of the SNPs were compared between the two populations. Results: A significant difference in oxygen saturation (SpO2) was observed between the two ethnic groups locating at different elevations (93.7 ± 0.2% in Sherpas at 3,440 m vs. 96.7 ± 0.2% in non-Sherpas at 1,300 m, P < 0.05). The plasma VEGF-A concentration in the Sherpas at high altitude was on the same level as that in the non-Sherpas at low altitude (262.8 ± 17.9 pg/ml vs. 266.8 ± 21.8 pg/ml, P = 0.88). This result suggested that the plasma VEGF-A concentration in Sherpa highlanders was stable despite a high-altitude hypoxic stimulus and that therefore the Sherpas exhibited a phenotype of blunted response to hypoxic stress. Moreover, the allele frequencies of the SNPs rs699947, rs833061, and rs2010963 in the promoter region of the VEGFA were different between the Sherpa highlanders and non-Sherpa lowlanders (corrected P values = 3.30 ×10-5, 4.95 ×10-4, and 1.19 ×10-7, respectively). Conclusions: Sherpa highlanders exhibited a blunted VEGF-A response to hypoxia at high altitudes, which was speculated to be associated with the distinctive genetic variations of the SNPs and haplotype in the promoter region of VEGFA in Sherpa highlanders.


Assuntos
Doença da Altitude , Humanos , Doença da Altitude/genética , Fator A de Crescimento do Endotélio Vascular/genética , Microcirculação/fisiologia , Hipóxia/genética , Regiões Promotoras Genéticas/genética
6.
PLoS One ; 17(7): e0271129, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35862393

RESUMO

OBJECTIVE: To generate appropriate reference values for the single-breath diffusing capacity of the lungs for carbon monoxide (DLCO), alveolar volume (VA), and the transfer coefficient of the lungs for carbon monoxide (KCO, often denoted as DLCO/VA) in the Japanese population. We also intended to assess the applicability of these values for the Japanese population by comparing them to those published by the Global Lung Function Initiative in 2017 (GLI-2017) and previous values. METHODS: In this retrospective study, we measured the spirometric indices, DLCO, VA, and KCO of the Japanese population aged 16-85 years. The lambda, mu, and sigma (LMS) method and the generalized additive models for the location, scale, and shape program in R were used to generate the reference values. RESULTS: We conducted a total of 390 tests. The GLI-2017 z-scores of DLCO were approximately zero, whereas those of KCO and VA were far from zero. In the present study, the mean square errors of the DLCO, VA, and KCO reference values were lower than the reference values derived from GLI-2017 and previous linear regression equations. CONCLUSIONS: Reference values obtained in this study were more appropriate for our sample than those reported in GLI-2017. Differences between the two equations were attributed to underestimating KCO (DLCO / VA) and overestimating VA, respectively, by the GLI-2017 for the Japanese population.


Assuntos
Monóxido de Carbono , Capacidade de Difusão Pulmonar , Monóxido de Carbono/análise , Humanos , Japão , Pulmão , Estudos Retrospectivos
7.
Int J Chron Obstruct Pulmon Dis ; 17: 1443-1452, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35761955

RESUMO

Purpose: The associations between morphological phenotypes of COPD based on the chest computed tomography (CT) findings and clinical characteristics in surgically resected patients with COPD and concomitant lung cancer are unclear. The purpose of this study was to clarify the differences in clinical characteristics and prognosis among morphological phenotypes based on the chest CT findings in these patients. Patients and Methods: We retrospectively reviewed the medical records of 132 patients with COPD and concomitant lung cancer who had undergone pulmonary resection for primary lung cancer. According to the presence of emphysema and bronchial wall thickness on chest CT, patients were classified into three phenotypes: non-emphysema phenotype, emphysema phenotype, or mixed phenotype. Results: The mixed phenotype was associated with poorer performance status, higher score on the modified British Medical Research Council (mMRC) dyspnea scale, higher residual volume in pulmonary function, and higher proportion of squamous cell carcinoma than the other phenotypes. Univariate and multivariate Cox proportional hazards regression analyses showed that the extent of emphysema on chest CT, presented as a low attenuation area (LAA) score, was an independent determinant that predicted prognosis. In the Kaplan-Meier analysis, the Log rank test showed significant differences in survival between the non-emphysema and mixed phenotypes, and between the emphysema and mixed phenotypes. Conclusion: The cross-sectional pre-operative LAA score can predict the prognosis in surgically resected patients with COPD and concomitant lung cancer. The COPD phenotype with both emphysema and bronchial wall thickness on chest CT was associated with poorer performance status, greater extent of dyspnea, greater impairment of pulmonary function, and worse prognosis.


Assuntos
Enfisema , Neoplasias Pulmonares , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Estudos Transversais , Dispneia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Fenótipo , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/cirurgia , Estudos Retrospectivos
8.
Respir Investig ; 60(4): 570-577, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35428607

RESUMO

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare multisystem disease with variable manifestations and differing rates of progression among individuals. Classification of its phenotypes is an issue for consideration. We hypothesized that clinical manifestations associated with LAM cluster together and identifying these associations would be useful for identifying phenotypes. METHODS: Using cross-sectional data from the National Database of Designated Intractable Diseases of Japan, we performed a hierarchical cluster analysis based on disease-associated manifestations. RESULTS: Four clusters were identified from 404 patients (50.4% of 801 LAM patients registered in 2016). Patients in cluster 1 had only dyspnea on exertion, relatively low lung function, the earliest onset age, and the lowest prevalence of tuberous sclerosis complex (TSC). Those in cluster 2 had various manifestations with the highest prevalence of TSC. Patients in cluster 3 had major respiratory symptoms (cough, sputum, or dyspnea on exertion) or fatigue and the lowest lung function. Those in cluster 4 were asymptomatic and had the latest onset age, shortest disease duration, and relatively high prevalence of TSC. Patients in cluster 1 had the highest rate of receiving mechanistic target of rapamycin (mTOR) inhibitor treatment, suggesting that cluster 1 included those with declining lung function for which mTOR inhibitor treatment was required. CONCLUSIONS: Hierarchical cluster analysis based on manifestations data identified four clusters. The characteristics of cluster 1 are noteworthy in relation to the indication for mTOR inhibitor treatment. A cluster analysis of accumulated and longitudinal data that allows valid clustering and outcome comparisons is required in the future.


Assuntos
Linfangioleiomiomatose , Esclerose Tuberosa , Análise por Conglomerados , Estudos Transversais , Dispneia/epidemiologia , Dispneia/etiologia , Humanos , Japão/epidemiologia , Linfangioleiomiomatose/diagnóstico , Linfangioleiomiomatose/epidemiologia , Doenças Raras/complicações , Serina-Treonina Quinases TOR , Esclerose Tuberosa/complicações , Esclerose Tuberosa/diagnóstico , Esclerose Tuberosa/epidemiologia
9.
Intern Med ; 61(17): 2637-2642, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35135925

RESUMO

A 69-year-old man was diagnosed with immunoglobulin (Ig) G4-related disease (IgG4-RD) at 62 years old. At that time, he had high serum IgG4 levels and bilateral submandibular gland swelling on CT; thus, a gland biopsy was performed. Because a reticular shadow was found on chest CT, a lung surgical biopsy was also performed. The specimens revealed usual interstitial pneumonia (UIP) pattern interstitial pneumonia with some IgG4-positive cells. The patient was subsequently followed up without treatment. His forced vital capacity and radiological findings progressively deteriorated, consistent with UIP pattern interstitial lung disease but different from a lung lesion of IgG4-RD.


Assuntos
Doenças Autoimunes , Fibrose Pulmonar Idiopática , Doença Relacionada a Imunoglobulina G4 , Doenças Pulmonares Intersticiais , Sialadenite , Idoso , Doenças Autoimunes/patologia , Doença Crônica , Humanos , Imunoglobulina G , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Sialadenite/complicações , Sialadenite/diagnóstico
10.
PLoS One ; 17(2): e0262795, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35113907

RESUMO

Idiopathic pulmonary fibrosis (IPF), a fibrosing interstitial lung disease, predominantly affects the elderly and is associated with a high mortality risk. Nintedanib, a tyrosine kinase inhibitor, significantly reduces IPF progression. However, data on the tolerability and efficacy of nintedanib in the elderly with IPF are limited. Therefore, this study aimed to examine the tolerability and efficacy of nintedanib in the elderly with IPF in a real-world setting. Medical records of 19 elderly IPF patients (≥ 75 years) and 46 non-elderly IPF patients (< 75 years) newly administered nintedanib were retrospectively analyzed. We compared the forced vital capacity (FVC) level, incidence and severity of adverse events, and continuation rates of nintedanib between the two groups. FVC and percent predicted diffusing capacity of the lung for carbon monoxide (DLco) were lower in the elderly IPF group at baseline. Although the elderly IPF patients had a significantly higher incidence of adverse events, such as diarrhea, nausea, and elevation of hepatic enzymes, the rate of discontinuation of nintedanib owing to adverse events was not different between the groups. The continuation rates of nintedanib treatment at 6 months and 1 year in the elderly IPF group were equivalent. Furthermore, there was a similar trend in the reduction of the annual FVC decline after nintedanib initiation between the groups. Our study demonstrated that nintedanib was tolerable in both the IPF patient groups in a real-world setting. Proper management of adverse events in the elderly with IPF would lead to a better clinical outcome.


Assuntos
Indóis
11.
Thorac Cancer ; 12(21): 2857-2864, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34599854

RESUMO

BACKGROUND: The quantity of skeletal muscles has recently been reported to have prognostic value in patients with non-small-cell lung cancer (NSCLC) treated with second-line immunotherapy. However, the prognostic role of skeletal muscle assessment in NSCLC patients undergoing first-line immuno-oncology (IO) combinatorial treatment (IO-chemotherapy) has not been elucidated. METHODS: We retrospectively reviewed 36 patients with NSCLC undergoing first-line IO-chemotherapy between April 2018 and June 2021 in our hospital. The cross-sectional area of the erector spinae muscle (ESMCSA ) was evaluated by manual tracing on computed tomography scans at the level of the 12th thoracic vertebra before initiating IO-chemotherapy. To minimize deviation due to physique, the ESMCSA was adjusted by body surface area (BSA) (ESMCSA to BSA ratio: ESMCSA /BSA). A survival time analysis was performed using the Kaplan-Meier method and log-rank test. A multivariate analysis with Cox proportional hazards model was conducted to investigate the prognostic value of the ESMCSA /BSA and inflammatory and nutritional indices. RESULTS: The median progression-free survival (PFS) and overall survival (OS) were 6.5 and 16.6 months, respectively. Intergroup comparison by the log-rank test revealed that there was no significant difference in the median PFS, but the median OS was significantly long in the high ESMCSA /BSA (>19 cm2/ m2 ) (high ESMCSA /BSA group, p = 0.0373). The multivariate analysis showed that ESMCSA /BSA was an independent prognostic factor for OS (hazard ratio 0.79, p = 0.044). CONCLUSIONS: The results of this study indicate that the pretreatment ESMCSA /BSA may be a potential prognostic factor in NSCLC patients receiving first-line IO-chemotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Tratamento Farmacológico/métodos , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Músculos Paraespinais/diagnóstico por imagem , Músculos Paraespinais/fisiopatologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Terapia Combinada , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos
12.
J Infect Chemother ; 27(12): 1706-1712, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34412984

RESUMO

INTRODUCTION: Risk factors for seriously ill coronavirus disease 19 (COVID-19) patients have been reported in several studies. However, to date, few studies have reported simple risk assessment tools for distinguishing patients becoming severely ill after initial diagnosis. Hence, this study aimed to develop a simple clinical risk nomogram predicting oxygenation risk in patients with COVID-19 at the first triage. METHODS: This retrospective study involved a chart review of the medical records of 84 patients diagnosed with COVID-19 between February 2020 and March 2021 at ten medical facilities. The patients were divided into requiring no oxygen therapy (non-severe group) and requiring oxygen therapy (severe group). Patient characteristics were compared between the two groups. We utilized univariate logistic regression analysis to confirm determinants of high risks of requiring oxygen therapy in patients with moderate COVID-19. RESULTS: Thirty-five patients ware in severe group and forty-nine patients were in non-severe group. In comparison with patients in the non-severe group, patients in the severe group were significantly older with higher body mass index (BMI), and had a history of hypertension and diabetes. Serum blood urea nitrogen (BUN), lactic acid dehydrogenase (LDH), and C-reactive protein (CRP) levels were significantly higher in the severe group. Multivariate analysis showed that older age, higher BMI, and higher BUN levels were significantly associated with oxygen requirements. CONCLUSIONS: This study demonstrated that age, BMI, and BUN were independent risk factors in the moderate-to-severe COVID-19 group. Elderly patients with higher BMI and BUN require close monitoring and early treatment initiation.


Assuntos
COVID-19 , Idoso , Nitrogênio da Ureia Sanguínea , Índice de Massa Corporal , Humanos , Oxigênio , Prognóstico , Estudos Retrospectivos , SARS-CoV-2
13.
J Comput Assist Tomogr ; 45(4): 649-658, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34176875

RESUMO

OBJECTIVE: Several software-based quantitative computed tomography (CT) analysis methods have been developed for assessing emphysema and interstitial lung disease. Although the texture classification method appeared to be more successful than the other methods, the software programs are not commercially available, to our knowledge. Therefore, this study aimed to investigate the usefulness of a commercially available software program for quantitative CT analyses. METHODS: This prospective cohort study included 80 patients with chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF). RESULTS: The percentage of low attenuation volume and high attenuation volume had high sensitivity and high specificity for detecting emphysema and pulmonary fibrosis, respectively. The percentage of diseased lung volume (DLV%) was significantly correlated with the lung diffusion capacity for carbon monoxide in all patients with COPD and IPF patients. CONCLUSIONS: The quantitative CT analysis may improve the precision of the assessment of DLV%, which itself could be a useful tool in predicting lung diffusion capacity in patients with the clinical diagnosis of COPD or IPF.


Assuntos
Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/patologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/patologia , Tomografia Computadorizada por Raios X/métodos , Idoso , Estudos de Coortes , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Medidas de Volume Pulmonar , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
14.
Respir Res ; 22(1): 150, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33992109

RESUMO

BACKGROUND: IL-33, which is known to induce type 2 immune responses via group 2 innate lymphoid cells, has been reported to contribute to neutrophilic airway inflammation in chronic obstructive pulmonary disease. However, its role in the pathogenesis of emphysema remains unclear. METHODS: We determined the role of interleukin (IL)-33 in the development of emphysema using porcine pancreas elastase (PPE) and cigarette smoke extract (CSE) in mice. First, IL-33-/- mice and wild-type (WT) mice were given PPE intratracheally. The numbers of inflammatory cells, and the levels of cytokines and chemokines in the bronchoalveolar lavage (BAL) fluid and lung homogenates, were analyzed; quantitative morphometry of lung sections was also performed. Second, mice received CSE by intratracheal instillation. Quantitative morphometry of lung sections was then performed again. RESULTS: Intratracheal instillation of PPE induced emphysematous changes and increased IL-33 levels in the lungs. Compared to WT mice, IL-33-/- mice showed significantly greater PPE-induced emphysematous changes. No differences were observed between IL-33-/- and WT mice in the numbers of macrophages or neutrophils in BAL fluid. The levels of hepatocyte growth factor were lower in the BAL fluid of PPE-treated IL-33-/- mice than WT mice. IL-33-/- mice also showed significantly greater emphysematous changes in the lungs, compared to WT mice, following intratracheal instillation of CSE. CONCLUSION: These observations suggest that loss of IL-33 promotes the development of emphysema and may be potentially harmful to patients with COPD.


Assuntos
Interleucina-33/deficiência , Pulmão/metabolismo , Elastase Pancreática , Pneumonia/metabolismo , Enfisema Pulmonar/metabolismo , Fumaça , Produtos do Tabaco , Animais , Líquido da Lavagem Broncoalveolar/química , Modelos Animais de Doenças , Feminino , Fator de Crescimento de Hepatócito/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Interleucina-33/genética , Pulmão/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pneumonia/etiologia , Pneumonia/genética , Pneumonia/patologia , Enfisema Pulmonar/etiologia , Enfisema Pulmonar/genética , Enfisema Pulmonar/patologia
16.
Sci Rep ; 10(1): 12811, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32732977

RESUMO

The dominant pathogenesis underlying the combined pulmonary fibrosis and emphysema (CPFE) remains unresolved. The receptor for advanced glycation end-products (RAGE) is highly expressed in lung tissues and interacts with distinct multiple ligands, implicating it in certain lung diseases. To elucidate the pathogenesis of CPFE, we genotyped three single nucleotide polymorphisms (SNPs: rs2070600, rs1800625, and rs2853807) of the gene encoding RAGE (AGER) in 111 CPFE patients and 337 chronic obstructive pulmonary disease (COPD) patients of Japanese by using StepOne Real-Time PCR System for SNP genotyping assay. Serum levels of soluble RAGE (sRAGE) were measured by ELISA. We found that the allele frequency of rs2070600 was significantly different between the two groups [corrected P (Pc) = 0.015]. In addition, the minor allele was associated with CPFE patients relative to COPD patients in a dominant effect model (Odds Ratio = 1.93; Pc = 0.018). Moreover, the serum sRAGE level was significantly lower in the CPFE group than the COPD group (P = 0.014). The rs2070600 minor allele was significantly associated with reduced sRAGE level in CPFE patients and independently affected sRAGE level reduction in this group (P = 0.020). We concluded that the AGER rs2070600 minor allele (Gly82Ser mutation) is associated with the pathogenesis of pulmonary fibrosis in CPFE in Japanese patients.


Assuntos
Enfisema/genética , Mutação , Doença Pulmonar Obstrutiva Crônica/genética , Enfisema Pulmonar/genética , Fibrose Pulmonar/genética , Receptor para Produtos Finais de Glicação Avançada/genética , Idoso , Alelos , Povo Asiático , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptor para Produtos Finais de Glicação Avançada/metabolismo
17.
Int J Chron Obstruct Pulmon Dis ; 15: 1425-1434, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606651

RESUMO

Background: Obstructive ventilatory disturbances occur in both chronic obstructive pulmonary disease (COPD), a typical disease representative of peripheral airway obstruction, and central airway obstruction (CAO). Pulmonary function tests (PFTs), which depend on patient effort, are traditionally used to evaluate lung function. The forced oscillation technique (FOT) is an effort-independent method for examining lung function during tidal breathing. The FOT is used universally to assess respiratory function in patients with COPD. Several studies have measured FOT to assess ventilatory disturbances in CAO. The results showed that FOT measurements in patients with CAO were similar to those reported in patients with COPD. However, no studies have compared FOT measurements directly between CAO and COPD. The aim of this study was to identify differences in ventilatory disturbances between peripheral and central airway obstructions in COPD and CAO, before patients received pharmacological therapy or bronchoscopic interventions, respectively. Patients and Methods: We retrospectively included 16 patients with CAO (10 cases of tracheal obstruction and 6 cases of bronchial obstruction) and 75 treatment-naïve patients with COPD (60 cases in Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage II and 15 cases in GOLD stage III) that were admitted from December 2013 to May 2017. Prior to treatment, patients were examined with the FOT and PFTs. Results: All parameters measured with the FOT in the inspiratory phase were significantly worse in patients with CAO than in patients with COPD. The PFTs showed that the CAO group had a significantly lower peak expiratory flow rate. In the airway wall thickening phenotype of COPD, a difference between the inspiratory and expiratory phases of the resonance frequency (ΔFres) was the best indicator for distinguishing between peripheral and central airway obstructions. Conclusion: This study compared differences between CAO and COPD (mainly GOLD stage II). We found that the FOT measurement, ΔFres, was the optimal indicator of the difference between the airway wall thickening COPD phenotype and CAO. Thus, the difference might be due to mechanical changes that occur in COPD with airway wall thickening.


Assuntos
Obstrução das Vias Respiratórias , Doença Pulmonar Obstrutiva Crônica , Obstrução das Vias Respiratórias/diagnóstico , Obstrução das Vias Respiratórias/etiologia , Resistência das Vias Respiratórias , Volume Expiratório Forçado , Humanos , Oscilometria , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Testes de Função Respiratória , Estudos Retrospectivos
18.
Respir Med Case Rep ; 30: 101113, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32523870

RESUMO

A public health emergency of current international concern is the outbreak of a severe respiratory illness, that is, coronavirus disease (COVID-19). The disease initially started in Wuhan, China, and it rapidly spread to most regions of the world. Herein, we report a case of critical COVID-19 pneumonia treated with extracorporeal membrane oxygenation from symptom onset day 19 (SOD#19) to SOD#30. We describe the patient's clinical course, from mild symptoms at the time of illness onset to symptoms of severe pneumonia as the illness progressed. We provide important information regarding our clinical experience for further understanding of management discrepancies, as treatment with extracorporeal membrane oxygenation or pharmacotherapy (e.g., antivirals, immunomodulators, and glucocorticoids) is often dependent on the severity of symptoms.

19.
BMC Pulm Med ; 20(1): 144, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32434532

RESUMO

BACKGROUND: Previous analyses of combined pulmonary fibrosis and emphysema (CPFE) cohorts have provided conflicting data on the survival of patients with CPFE. Therefore, the aim of this study was to investigate the clinical prognosis of acute exacerbations (AE) of CPFE. METHODS: We retrospectively reviewed the medical records of patients who had been treated at the Shinshu University Hospital (Matsumoto, Japan) between 2003 and 2017. We identified 21 patients with AE of CPFE and 41 patients with AE of idiopathic pulmonary fibrosis (IPF) and estimated their prognoses using the Kaplan-Meier method. RESULTS: Treatment content and respiratory management were not significantly different between the two groups before and after exacerbation. At the time of AE, the median serum Krebs von den Lungen-6 level was significantly lower in the CPFE group (Krebs von den Lungen-6: 966 U/µL; white blood cell count: 8810 /µL) than that in the IPF group (Krebs von den Lungen-6: 2130 U/µL, p < 0.001; white blood cells: 10809/µL, p = 0.0096). The baseline Gender-Age-Physiology scores were not significantly different between the two groups (CPFE, 4.5 points; IPF, 4.7 points; p = 0.58). Kaplan-Meier curves revealed that the survival time after AE for patients with CPFE was longer than that for patients with IPF (p < 0.001, log-rank test). CONCLUSIONS: Survival prognoses after AE were significantly better for patients with CPFE than that for those with IPF. Our findings may improve the medical treatment and respiratory management of patients with AE-CPFE.


Assuntos
Fibrose Pulmonar Idiopática/epidemiologia , Enfisema Pulmonar/epidemiologia , Idoso , Progressão da Doença , Feminino , Humanos , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Japão , Masculino , Prognóstico , Enfisema Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Tomografia Computadorizada por Raios X
20.
Respiration ; 99(1): 9-18, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31554007

RESUMO

BACKGROUND: The interstitial lung disease-gender-age-physiology (ILD-GAP) index and staging system have been reported as a clinical prognostic factor for ILD, including all ILD subtypes. OBJECTIVES: The purpose of this study was to clarify the association of various prognostic indices, including the ILD-GAP index, with the prognosis, the incidence of acute exacerbations of ILD (ILD-AE), and the use of long-term oxygen therapy (LTOT) after surgery in surgically resected patients with ILD and concomitant lung cancer, to provide additional information when considering whether it is safe to perform surgery. METHODS: The medical records of patients with ILD and concomitant lung cancer who had undergone surgery at Shinshu University Hospital between August 2001 and September 2016 were retrospectively analyzed. RESULTS: There were significant differences in survival between the ILD-GAP index: 0-1 and ≥4 groups (p = 0.0001) and between the ILD-GAP index: 2-3 and ≥4 groups (p = 0.0236). A higher ILD-GAP index was independently associated with the risk of death (hazard ratio [HR] 1.32030; p = 0.0059). A higher body mass index (BMI) and a higher serum C-reactive protein (CRP) level were independently associated with the incidence of ILD-AE (HR 1.28336; p = 0.0206 and HR 26.3943; p = 0.0165, respectively). A higher severity of ILD on chest high-resolution computed tomography (HRCT) was independently associated with the use of LTOT (HR 2.78670; p = 0.0313). CONCLUSIONS: The ILD-GAP index can predict the prognosis in surgically resected patients with ILD and concomitant lung cancer. The BMI and serum CRP levels were independent determinants that predicted the incidence of ILD-AE. The severity of ILD on chest HRCT was an independent determinant that predicted the use of LTOT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Fibrose Pulmonar Idiopática/fisiopatologia , Doenças Pulmonares Intersticiais/fisiopatologia , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Fatores Etários , Idoso , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/patologia , Tomada de Decisão Clínica , Progressão da Doença , Feminino , Volume Expiratório Forçado , Humanos , Fibrose Pulmonar Idiopática/complicações , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/terapia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/patologia , Masculino , Mortalidade , Oxigenoterapia/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Modelos de Riscos Proporcionais , Capacidade de Difusão Pulmonar/fisiologia , Insuficiência Respiratória/epidemiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Sexuais , Capacidade Vital/fisiologia
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