RESUMEN
BACKGROUND: Evaluation of the antigen responsible for fibrotic hypersensitivity pneumonitis (HP) is challenging. Serum immunoglobulin (Ig) G testing against HP-associated antigens is performed. Although single-serum IgG testing has been investigated, multiple-serum IgG testing has not yet been studied. METHODS: This study included patients who underwent histopathological examination and positive inhalation challenge test as well as those with moderate or high HP guideline confidence level. Serum IgG testing against pigeon serum was conducted twice using two methods: enzyme linked-immunosorbent assay (ELISA) and ImmunoCAP. The association between changes in serum IgG antibody titers and changes in forced vital capacity (FVC) and other parameters was investigated. RESULTS: In this study, 28 patients (mean age, 64.5 years; mean FVC, 85.3%) with fibrotic avian HP were selected, of whom 20 and 8 underwent surgical lung biopsy and transbronchial lung cryobiopsy, respectively. Of the 28 patients, 19 had been keeping birds for more than 6 months. A correlation was observed between the annual changes in serum IgG antibody titers by ELISA and changes in relative FVC (r = - 0.6221, p < 0.001). Furthermore, there was a correlation between the annual changes in serum IgG antibody titers by ImmunoCAP and changes in relative FVC (r = - 0.4302, p = 0.022). Multiple regression analysis revealed that the change in serum IgG antibody titers by both ELISA and ImmunoCAP also influenced the relative FVC change (p = 0.012 and p = 0.015, respectively). Moreover, 13 patients were given additional treatments between the first and second blood test; however, the additional treatment group was not significantly different in relative FVC change compared to the group with no additional treatment (p = 0.982). CONCLUSIONS: In patients with fibrotic avian HP, the annual changes in serum IgG testing were correlated with FVC changes, highlighting the importance of serum IgG testing over time.
Asunto(s)
Pulmón de Criadores de Aves , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulina G , Humanos , Persona de Mediana Edad , Masculino , Femenino , Inmunoglobulina G/sangre , Anciano , Pulmón de Criadores de Aves/inmunología , Pulmón de Criadores de Aves/diagnóstico , Pulmón de Criadores de Aves/sangre , Animales , Capacidad Vital , Columbidae , Pulmón/patología , Pulmón/fisiopatología , Estudios Longitudinales , Alveolitis Alérgica Extrínseca/sangre , Alveolitis Alérgica Extrínseca/inmunología , Alveolitis Alérgica Extrínseca/diagnóstico , Alveolitis Alérgica Extrínseca/patologíaRESUMEN
Acute exacerbations due to COVID-19 vaccination in patients with interstitial lung disease (ILD) have been reported, but their incidence is unknown. We investigated the incidence of exacerbations of ILD and respiratory symptoms due to the mRNA COVID-19 vaccines. A questionnaire survey was conducted on adverse reactions to the mRNA COVID-19 vaccination in 545 patients with ILD attending our hospital and retrospectively examined whether the eligible patients actually developed acute exacerbations of ILD induced by the vaccine. Of the 545 patients, 17 (3.1%) patients were aware of the exacerbation of respiratory symptoms, and four (0.7%) patients developed an acute ILD exacerbation after vaccination. Of the four patients who experienced exacerbations, two had collagen vascular disease-associated ILD, one had nonspecific interstitial pneumonia, another had unclassifiable idiopathic pneumonia, and none had idiopathic pulmonary fibrosis. Four patients were treated using steroid pulse therapy with a steroid taper, and two of the four also received intravenous cyclophosphamide pulse therapy. Tacrolimus was started in one patient with myositis-associated interstitial lung disease. Eventually, all patients exhibited improvement with immunosuppressive treatment and were discharged. COVID-19 vaccination for patients with ILD should be noted for developing acute exacerbations of ILD with low incidence, although manageable with early diagnosis and treatment.
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Vacunas contra la COVID-19 , COVID-19 , Enfermedades Pulmonares Intersticiales , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Progresión de la Enfermedad , Incidencia , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/epidemiología , Enfermedades Pulmonares Intersticiales/etiología , Estudios Retrospectivos , ARN Mensajero , Vacunación/efectos adversosRESUMEN
The mutation status of tumor tissue DNA (n = 389) of resected stage II-III non-squamous non-small-cell lung cancer (Ns-NSCLC) was analyzed using targeted deep sequencing as an exploratory biomarker study (JIPANG-TR) for the JIPANG study, a randomized phase III study of pemetrexed/cisplatin (Pem/Cis) vs vinorelbine/cisplatin (Vnr/Cis). The TP53 mutation, common EGFR mutations (exon 19 deletion and L858R), and KRAS mutations were frequently detected. The frequency of the EGFR mutation was significant among female patients. Patients with an EGFR mutation-positive status had a significantly shorter recurrence-free survival (RFS) time (24 mo vs not reached) (HR, 1.64; 95% CI, 1.22-2.21; P = .0011 for EGFR mutation status). Multivariable analysis identified both the pathological stage and EGFR mutation status as independent prognostic factors for RFS (HR, 1.78; 95% CI, 1.30-2.44; P = .0003 for disease stage; and HR, 1.57; 95% CI, 1.15-2.16; P = .0050 for EGFR mutation status). This study demonstrated that the EGFR mutation has either a poor prognostic or predictive impact on a poor response to postoperative chemotherapy with platinum doublet chemotherapy for stage II-III Ns-NSCLC patients. This result supports a role for mandatory molecular diagnosis of early-stage Ns-NSCLC for precision oncology and signifies the importance of adjuvant for the 3rd generation tyrosine kinase inhibitor rather than platinum-based chemotherapy. This study is registered with the UMIN Clinical Trial Registry (UMIN 000012237).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Mutación , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Quimioterapia Adyuvante , Cisplatino/uso terapéutico , Receptores ErbB/genética , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Masculino , Pemetrexed/uso terapéutico , Medicina de Precisión , Pronóstico , Análisis de Secuencia de ADN , Análisis de Supervivencia , Resultado del Tratamiento , Vinorelbina/uso terapéuticoRESUMEN
This prespecified subanalysis of the global, randomized controlled phase III KEYNOTE-024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non-small-cell lung cancer without EGFR/ALK alterations and a programmed death-ligand 1 (PD-L1) tumor proportion score of 50% or greater evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum-based chemotherapy (four to six cycles). The primary end-point was progression-free survival; secondary end-points included overall survival and safety. Of 305 patients randomized in KEYNOTE-024 overall, 40 patients were enrolled in Japan (all received treatment: pembrolizumab, n = 21; chemotherapy, n = 19). The hazard ratio (HR) for progression-free survival by independent central review (data cut-off date, 10 July 2017) was 0.25 (95% confidence interval [CI], 0.10-0.64; one-sided, nominal P = .001). The HR for overall survival (data cut-off date, 15 February 2019) was 0.39 (95% CI, 0.17-0.91; one-sided, nominal P = .012). Treatment-related adverse events occurred in 21/21 (100%) pembrolizumab-treated and 18/19 (95%) chemotherapy-treated patients; eight patients (38%) and nine patients (47%), respectively, had grade 3-5 events. Immune-mediated adverse events and infusion reactions occurred in 11 patients (52%) and four patients (21%), respectively; four patients (19%) and one patient (5%), respectively, had grade 3-5 events. Consistent with results from KEYNOTE-024 overall, first-line pembrolizumab improved progression-free survival and overall survival vs chemotherapy with manageable safety among Japanese patients with metastatic non-small-cell lung cancer without EGFR/ALK alterations and a PD-L1 tumor proportion score of 50% or greater. The trial is registered with ClinicalTrials.gov: NCT02142738.
Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos Inmunológicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Carboplatino/uso terapéutico , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Quimioterapia , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pemetrexed/administración & dosificación , Pemetrexed/uso terapéutico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
The JIPANG study is a randomized phase III study of pemetrexed/cisplatin (Pem/Cis) versus vinorelbine/cisplatin (Vnr/Cis) for completely resected stage II-IIIA non-squamous non-small cell lung cancer (Ns-NSCLC). This study did not meet the primary endpoint (recurrence-free survival, RFS) but Pem/Cis had a similar efficacy to Vnr/Cis with a better tolerability. Tumor mutation burden (TMB) is thought to have a predictive value of immune checkpoint inhibitors. However, the relevance of TMB to cytotoxic chemotherapy remains unknown. This exploratory study investigates the relationship between tumor mutation profiles and clinical outcome of Pem/Cis. Formalin-fixed, paraffin-embedded tumor tissues (n = 389) were obtained from the patients. Mutation status of tissue DNA was analyzed by targeted deep sequencing. Epidermal growth factor receptor (EGFR) mutations were detected frequently in Ns-NSCLC (139/374). Patients without any EGFR mutations experienced longer RFS in the Pem/Cis arm versus Vnr/Cis arms. Pem/Cis in patients with high TMB (≥12-16 mut/Mb) tended to have improved survival. In patients with wild-type EGFR, TMB ≥ 12 mut/Mb was significantly associated with improved RFS with Pem/Cis versus Vnr/Cis (not reached vs 52.5 months; hazard ratio (HR) 0.477). It could be proposed that TMB was predictive of RFS benefit with Pem/Cis versus Vnr/Cis in Ns-NSCLC. Further investigation is required to determine whether TMB combined with EGFR mutation status could be used as a predictive biomarker.
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Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Cisplatino/administración & dosificación , Neoplasias Pulmonares/genética , Pemetrexed/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Análisis Mutacional de ADN , Receptores ErbB/genética , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Mutación , Resultado del TratamientoRESUMEN
BACKGROUND: A subset analysis of the CA031 trial showed significant improvement in the overall response rate after administration of carboplatin plus weekly albumin-bound paclitaxel compared to carboplatin plus paclitaxel for squamous cell carcinoma of the lung (SQ). We conducted this phase II study to compare carboplatin plus weekly albumin-bound paclitaxel (CnP) to cisplatin plus gemcitabine (CG), a standard regimen for SQ. METHODS: Chemotherapy-naïve patients with SQ were randomly assigned to receive cisplatin (80 mg/m2) on day 1 plus gemcitabine (1000 mg/m2) on days 1 and 8 every 3 weeks or carboplatin (area under the curve: 6 mg/mL/min) on day 1 plus nab-paclitaxel (75 mg/m2) on days 1, 8, and 15 every 3 weeks. The primary endpoint was overall response rate. The secondary endpoints were progression-free survival, overall survival, disease control rate, and toxicity. RESULTS: Between June 2013 and October 2018, 71 patients were enrolled and assigned to either the CG arm (n = 35) or the CnP arm (n = 36) of the study. The overall response rate was 43% [95% confidence interval (CI) 27.3-58.5] in the CG arm and 47% (95% CI 31.7-62.7) in the CnP arm. Although drug combination efficacies did not differ, there were differences in toxicity: hematologic toxicities (leukopenia, neutropenia, and thrombocytopenia) were found mostly in the CG arm, whereas anemia and sensory neuropathy were more common in the CnP arm. CONCLUSIONS: CnP had similar response as CG despite being a carboplatin-based regimen and toxicities differed between arms. Regarding ORR, CnP was comparable to CG for SQ.
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Carcinoma de Células Escamosas , Neoplasias Pulmonares , Albúminas , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/efectos adversos , Carcinoma de Células Escamosas/tratamiento farmacológico , Cisplatino/efectos adversos , Desoxicitidina/análogos & derivados , Humanos , Japón , Neoplasias Pulmonares/tratamiento farmacológico , Paclitaxel/efectos adversos , Resultado del Tratamiento , GemcitabinaRESUMEN
This prespecified subanalysis of the global, randomized controlled phase III KEYNOTE-024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non-small-cell lung cancer without EGFR/ALK alterations and a programmed death ligand 1 (PD-L1) tumor proportion score of 50% or higher evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum-based chemotherapy (four to six cycles). The primary end-point was progression-free survival; secondary end-points included overall survival and safety. Of 305 patients randomized in KEYNOTE-024 overall, 40 patients were enrolled in Japan (all received treatment: pembrolizumab, n = 21; chemotherapy, n = 19). Median progression-free survival was 41.4 (95% confidence interval [CI], 4.2-42.5) months with pembrolizumab and 4.1 (95% CI, 2.8-8.3) months with chemotherapy (hazard ratio [HR], 0.27 [95% CI, 0.11-0.65]; one-sided, nominal P = .001). Median overall survival was not reached (NR) (95% CI, 22.9-NR) and 21.5 (95% CI, 5.2-35.0) months, respectively (HR, 0.39 [95% CI, 0.17-0.91]; one-sided, nominal P = .012). Treatment-related adverse events occurred in 21/21 (100%) pembrolizumab-treated and 18/19 (95%) chemotherapy-treated patients; eight patients (38%) and nine patients (47%), respectively, had grade 3-5 events. Immune-mediated adverse events and infusion reactions occurred in 11 pembrolizumab-treated patients (52%) and four chemotherapy-treated patients (21%), respectively; four patients (19%) and one patient (5%), respectively, had grade 3-5 events. Consistent with results from KEYNOTE-024 overall, first-line pembrolizumab improved progression-free survival and overall survival vs chemotherapy with manageable safety among Japanese patients with metastatic non-small-cell lung cancer without EGFR/ALK alterations and a PD-L1 tumor proportion score of 50% or higher. The trial is registered with Clinicaltrials.gov: NCT02142738.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Quinasa de Linfoma Anaplásico/genética , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Cisplatino/administración & dosificación , Intervalos de Confianza , Estudios Cruzados , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Esquema de Medicación , Femenino , Genes erbB-1 , Humanos , Japón , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Pemetrexed/administración & dosificación , Receptor de Muerte Celular Programada 1 , Supervivencia sin Progresión , Resultado del Tratamiento , GemcitabinaRESUMEN
INTRODUCTION: Bronchial thermoplasty (BT) improves asthma-related quality of life and decreases the number of asthma exacerbations. However, the effectiveness of BT in the treatment of severe asthma with smoking history is unclear because previous studies have excluded patients with smoking history of more than 10 pack-years. OBJECTIVE: The aim of the study was to clarify the effectiveness and safety of BT for severe asthma with smoking history. METHODS: We retrospectively reviewed patients who received BT and compared its effectiveness and safety with and without smoking history. RESULTS: Seven patients were assigned to the smoking group and 9 to the nonsmoking group. Before BT, despite Global Initiative for Asthma step 4 or 5 treatment including oral corticosteroids (OCS) or monoclonal antibody drugs, most patients in both groups had asthma-related symptoms every day (85.7 vs. 77.8%; p = 0.475) and frequent asthma exacerbations. After BT, in the smoking group, 3 patients could discontinue or reduce OCS and all 3 patients treated with monoclonal antibody drugs could discontinue them. In the smoking group, 6 patients (85.7%) experienced a reduction in the rate of symptoms, of which 3 patients (42.9%) had a disappearance of symptoms, similar to the nonsmoking group. BT was effective in 5 patients (83.3%) in the smoking group and 6 patients (75.0%) in the nonsmoking group. There were no severe complications. CONCLUSIONS: BT was found to be effective and safe for treatment of severe asthma with smoking history. Our results suggest that BT may be a therapeutic option for asthma-chronic obstructive pulmonary disease overlap.
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Asma/etiología , Asma/terapia , Termoplastia Bronquial/métodos , Fumar/efectos adversos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by deteriorated exocrine gland function with associated lymphocytic infiltration. However, there are few pathological studies on bronchial glands in SS. In this study, we aimed to clarify pathological features of bronchial glands in SS. METHODS: We retrospectively evaluated infiltration of lymphocytes in the bronchial glands incidentally collected by transbronchial lung cryobiopsy (TBLC), which were performed for the diagnosis of diffuse lung diseases. The degrees of lymphocyte infiltration in the bronchial glands were classified into four grades (grade 0-3). We compared the degrees of infiltration of SS with those of other diffuse lung diseases. RESULTS: TBLC for diagnosis of diffuse lung diseases were performed on 432 cases during the study period. The samples of 50 cases included bronchial glands. Of those, 20 cases were excluded due to insufficient size or influence of therapy. The remaining 30 cases included 17 of idiopathic interstitial pneumonias, 5 of chronic hypersensitivity pneumonia, 6 of connective tissue disease (SS; n = 4, systemic sclerosis; n = 1, dermatomyositis; n = 1) and 2 of other diseases. In SS, infiltration of lymphocytes was observed in all cases; grade 1 in one, grade 2 in one, and grade 3 in two cases. In contrast, 11 of 26 in other diseases showed no lymphocytes infiltration, with the remaining 15 of grade 1 infiltration. Grade 2 or more infiltration were found only in SS but not in other diseases. CONCLUSION: Our results suggested that high-grade lymphocytic infiltration of bronchial glands is a distinct characteristics in SS.
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Biopsia/instrumentación , Criocirugía , Glándulas Exocrinas/patología , Linfocitos/patología , Síndrome de Sjögren/patología , Adulto , Anciano , Anciano de 80 o más Años , Biopsia/métodos , Bronquios/patología , Broncoscopía/métodos , Diagnóstico Diferencial , Femenino , Humanos , Pulmón/patología , Enfermedades Pulmonares/diagnóstico , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Pyrazinamide (PZA) -including regimen had not been fully recommended for late elderly patients with tuberculosis (TB) by Japanese Society for Tuberculosis until 2018. Studies on the safety of adding PZA to other first-line TB drugs for late elderly patients are limited. In this prospective randomized open-label study, we aimed to assess the safety of regimen including PZA for patients aged 80 or older. Patients in their eighties with smear-positive pulmonary TB without any liver diseases were randomly assigned to HRE (isoniazid, rifampicin, ethambutol) group or HREZ (HRE and PZA) group. The primary endpoint was discontinuation or interruption rate of treatment due to liver injury. Other endpoint included overall rate of liver injury, time to culture conversion, and overall mortality. Eighty-nine patients were assigned to either HRE group (n = 45) or HREZ group (n = 44). Clinical background was not different in two groups including age, smear grade, body weight, serum albumin, and activity degree. Discontinuation of treatment due to liver injury occurred in 15.6% of HRE group and 9.1% of HREZ group, which showed no statistical difference. Incidence of liver injury was also comparable between two groups. Overall mortality was statistically higher in HREZ group (3 in HRE vs. 10 in HREZ), although all deaths seemed to be irrelevant to PZA use. Time to culture conversion was significantly shorter in HREZ group (43.6 days vs. 30.2 days). In conclusion, regimen including PZA seems to be safe for late elderly patients with pulmonary TB.
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Antituberculosos/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Mycobacterium tuberculosis/aislamiento & purificación , Pirazinamida/efectos adversos , Tuberculosis Pulmonar/tratamiento farmacológico , Factores de Edad , Anciano de 80 o más Años , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Etambutol/efectos adversos , Femenino , Humanos , Incidencia , Isoniazida/efectos adversos , Masculino , Estudios Prospectivos , Rifampin/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/mortalidadRESUMEN
BACKGROUND: Current clinical practice guidelines for idiopathic pulmonary fibrosis (IPF) conditionally recommend use of pirfenidone and nintedanib. However, an optimal treatment sequence has not been established, and the data of treatment sequence from pirfenidone to nintedanib are limited. This study aimed to evaluate safety, tolerability and efficacy of nintedanib switched from pirfenidone in patients with IPF. METHODS: Thirty consecutive IPF cases, which discontinued pirfenidone because of a decline in forced vital capacity (FVC) or intolerable adverse event (AE), and newly started nintedanib (150 mg twice daily) from September 2015 to August 2017 (switch-group) were retrospectively reviewed. Subsequently, we compared the characteristics, treatment status, and AEs between the switch-group and other 64 IPF patients newly started nintedanib during the same period without any prior anti-fibrotic treatment (pirfenidone-naïve group). RESULTS: In the switch group, median age, body weight, body mass index (BMI), and %FVC were 72 years old, 54.9 kg, 21.0 kg/m2, and 52.9%, respectively. Most common AE of nintedanib was aspartate aminotransferase/alanine aminotransferase elevation (71.9%), followed by anorexia (46.7%) and diarrhea (46.7%); whereas, anorexia (63.3%) and ≥ 5% weight loss from baseline (56.7%) were common during pirfenidone administration. Sixteen patients (53.3%) discontinued nintedanib within 6 months (early termination). Multivariate logistic regression analysis revealed a significant association between low BMI and early nintedanib termination in the switch-group (p = 0.0239). Nintedanib suppressed FVC decline as compared with that during administration period of pirfenidone in 70% of the patients who could undergo lung function before and after switching to nintedanib. The incidence of early termination of nintedanib was higher in the switch-group than in the pirfenidone-naïve group, whereas body-weight, BMI, absolute FVC values, and %FVC were significantly lower in the switch-group (just before nintedanib initiation) than in the pirfenidone-naïve group. Nintedanib-induced anorexia was more frequent and severer in the switch-group than in the pirfenidone-naïve group, but no significant differences were observed in terms of other AEs. CONCLUSIONS: A high incidence of early termination of nintedanib was noted when patients were switched from pirfenidone. Anorexia and weight loss during prior pirfenidone administration may increase the rate of the early termination of subsequent nintedanib treatment.
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Anorexia/inducido químicamente , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Indoles/administración & dosificación , Piridonas/efectos adversos , Anciano , Femenino , Humanos , Fibrosis Pulmonar Idiopática/fisiopatología , Indoles/efectos adversos , Japón , Modelos Logísticos , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Resultado del Tratamiento , Capacidad Vital/efectos de los fármacos , Pérdida de Peso/efectos de los fármacosRESUMEN
BACKGROUND: Preclinical studies have demonstrated that docetaxel and bevacizumab may act synergistically by decreasing endothelial cell proliferation and preventing circulating endothelial progenitor mobilization. The objective of this study was to assess the efficacy and safety of a combination therapy of bevacizumab, cisplatin, and docetaxel in chemotherapy-naive Japanese patients with advanced non-squamous non-small-cell lung cancer (NSCLC). METHODS: Eligible patients were chemotherapy-naive and had advanced/recurrent non-squamous NSCLC. The patients received 4 cycles of docetaxel (60 mg/m2), cisplatin (80 mg/m2), and bevacizumab (15 mg/kg) once every 3 weeks, followed by bevacizumab as maintenance therapy, every 3 weeks until disease progression or attainment of unacceptable toxicity level. The primary endpoint was objective response rate (ORR). The numbers of circulating endothelial cells (CEC) were also estimated on days 1 and 8 of the first cycle for the exploratory analysis of efficacy prediction. RESULTS: A total of 47 patients were enrolled from October 2010 to April 2012. Bevacizumab as maintenance therapy was administered to 41 patients (87.2%), and the median number of total treatment cycles was 9 (range: 1-36). ORR, median progression-free survival (PFS), and median overall survival of the patients were 74.5%, 9.0 months, and 27.5 months, respectively. The most common grade 3/4 adverse event was neutropenia (95.7%), followed by leukopenia (59.6%) and hypertension (46.8%). PFS was longer in patients with ≥10 count increase in CECs than that in patients with < 10 count increase in CECs (respective median PFS of 11.0 months versus 6.90 months) although the difference was not statistically significant (p = 0.074). CONCLUSIONS: A combination therapy of bevacizumab, cisplatin, and docetaxel, followed by bevacizumab as maintenance was highly effective in patients with non-squamous NSCLC despite the high incidence of grade 3/4 neutropenia. The increase in CEC count between days 1 and 8 may predict the efficacy of our bevacizumab-contained treatment regimen. TRIAL REGISTRATION: UMIN Clinical Trial Registry; UMIN000004368 . Registered date; October 11, 2010 (Retrospectively registered).
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Células Endoteliales/patología , Neoplasias Pulmonares/tratamiento farmacológico , Células Neoplásicas Circulantes/patología , Adenocarcinoma/sangre , Adenocarcinoma/patología , Adulto , Anciano , Bevacizumab/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/patología , Cisplatino/administración & dosificación , Docetaxel , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Taxoides/administración & dosificaciónRESUMEN
BACKGROUND AND OBJECTIVE: Non-specific interstitial pneumonia (NSIP) has heterogeneous characteristics in terms of background, disease behaviour and prognosis. This study of fibrotic NSIP (f-NSIP) aimed to elucidate prognosis and disease behaviour from the viewpoint of clinical background and determine whether long-term change of pulmonary function could provide useful prognostic information. METHODS: We analysed the medical records of 157 consecutive patients diagnosed with f-NSIP by surgical lung biopsy. Disease behaviour was categorized into two groups depending on long-term change of pulmonary function: progressive type (relative ≥5%/year decline in the slope of forced vital capacity and/or relative ≥7.5%/year decline in the slope of %diffusing capacity of lung carbon monoxide) or stable type. Predictors of disease behaviour and prognosis were determined using logistic and Cox regression models. RESULTS: Our f-NSIP cohort included interstitial pneumonia with autoimmune features (IPAF) (36.9%), idiopathic (non-IPAF) (22.3%) and connective tissue disease-associated interstitial lung disease (40.8%). Multivariate analysis showed that idiopathic (non-IPAF) f-NSIP and progressive type disease were negative prognostic factors of mortality. Poor treatment response at 1 year was an independent predictor of progressive type disease, but was not related to survival. In terms of disease behaviour based on pulmonary function change, some patients with IPAF f-NSIP showed a progressive course. CONCLUSION: Although an IPAF diagnosis was useful for identifying good prognosis in idiopathic f-NSIP, some idiopathic f-NSIP patients with or without IPAF showed progressive disease despite therapy. The definition of progressive type disease may be useful in clinical decision-making when determining therapy for f-NSIP.
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Biopsia/métodos , Enfermedades Pulmonares Intersticiales , Fibrosis Pulmonar , Anciano , Autoinmunidad , Estudios de Cohortes , Enfermedades del Tejido Conjuntivo/diagnóstico , Enfermedades del Tejido Conjuntivo/patología , Femenino , Humanos , Pulmón/patología , Pulmón/fisiopatología , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/patología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Fibrosis Pulmonar/diagnóstico , Fibrosis Pulmonar/patología , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: Little has been reported on long-term pulmonary function trends among patients with interstitial lung disease associated with anti-aminoacyl-tRNA synthetase antibodies (ARS-ILD). OBJECTIVES: To clarify the factors predictive of progression in ARS-ILD based on patients' initial clinical and radiological features. METHODS: The clinical courses of 88 patients with > 1 year of follow-up data on pulmonary function tests (PFTs) were retrospectively analyzed. Disease behavior was categorized into three groups: (1) improved or (2) worsened (defined as increases or decreases, respectively, of > 10% in forced vital capacity and > 15% in %diffusing capacity of lung carbon monoxide) or (3) stable based on PFT changes compared between 1-year results as the initial data and results at 3 years to assess the long-term course. RESULTS: In the initial course of 75 patients with ARS-ILD who received anti-inflammatory therapy within 6 months after diagnosis, 48 patients (64.0%) improved and 6 patients (8.0%) worsened. The radiological patterns in the patients with ARS-ILD included nonspecific interstitial pneumonia (NSIP) in 46.7% and NSIP with organizing pneumonia overlap in 52.0% of the cases. One-third of the initially improved patients who worsened over the long-term course were assigned to the unstable group. By multivariate logistic analysis, middle lobe traction bronchiectasis was a significant predictive factor for the patients in the unstable group. CONCLUSIONS: Most patients with ARS-ILD receiving anti-inflammatory therapy had improved or remained stable in the first year. However, over the long-term course, some patients worsened despite their initial improvement. Even though the extent of the disease is limited, middle lobe traction bronchiectasis in ARS-ILD may be a useful predictor of poor long-term disease behavior.
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Aminoacil-ARNt Sintetasas/inmunología , Enfermedades Pulmonares Intersticiales/fisiopatología , Pulmón/fisiopatología , Anciano , Antiinflamatorios/uso terapéutico , Progresión de la Enfermedad , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/inmunología , Masculino , Persona de Mediana Edad , Radiografía Torácica , Pruebas de Función Respiratoria , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Pulmonary emphysema combined with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) occurs more often in smokers but also in never-smokers. This study aimed to describe a new finding characterized by peculiar emphysematous change with SSc-associated ILD (SSc-ILD). METHODS: We conducted a retrospective review of 21 consecutive patients with SSc-ILD diagnosed by surgical lung biopsy and focused on the radio-pathological correlation of the emphysematous change. RESULTS: Pathological pulmonary emphysema (p-PE) with SSc-ILD was the predominant complication in 16 patients (76.2%) with/without a smoking history, of whom 62.5% were never-smokers. A low attenuation area (LAA) within interstitial abnormality on high-resolution computed tomography (HRCT) was present in 31.3%. Diffusing capacity of the lung for carbon monoxide (DLCO) was lower, disease extent on HRCT higher, and intimal/medial thickening in muscular pulmonary arteries more common in the patients with p-PE with SSc-ILD. However, forced vital capacity (FVC) was well preserved regardless of whether p-PE was observed. Most SSc-ILD patients had pulmonary microvasculature changes in arterioles (90.5%), venules (85.7%), and interlobular veins (81.0%). CONCLUSIONS: Pulmonary emphysematous changes (LAA within interstitial abnormalities on HRCT and destruction of fibrously thickened alveolar walls) are specific and novel radio-pathological features of SSc-ILD. Peripheral vasculopathy may help to destroy the fibrously thickened alveolar walls, resulting in emphysematous change in SSc-ILD.
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Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Pulmón/irrigación sanguínea , Microvasos/patología , Arteria Pulmonar/patología , Enfisema Pulmonar/diagnóstico por imagen , Esclerodermia Sistémica/complicaciones , Anciano , Monóxido de Carbono , Femenino , Volumen Espiratorio Forzado , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Pulmón/fisiopatología , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/patología , Enfermedades Pulmonares Intersticiales/fisiopatología , Masculino , Persona de Mediana Edad , Capacidad de Difusión Pulmonar , Enfisema Pulmonar/etiología , Enfisema Pulmonar/patología , Enfisema Pulmonar/fisiopatología , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Túnica Íntima/patología , Enfermedades Vasculares/patología , Capacidad VitalRESUMEN
AIMS: There have been few reports on immunoglobulin-G4 (IgG4)-related interstitial pneumonia (IP), and its clinical features remain unclear. The objective of this study was to assess whether IP with marked IgG4-positive plasma cell infiltration without extrathoracic lesions of IgG4-related disease (RD) should be diagnosed as a subtype of IgG4-RD or a separate entity. METHODS AND RESULTS: All consecutive patients with surgical lung biopsy-proven idiopathic IP with an IgG4/IgG-positive cell ratio of >40% and >50 IgG4+ plasma cells in a high-power field without extrathoracic lesions of IgG4-RD were reviewed retrospectively. Five patients were enrolled into this study. All patients were male with a history of smoking. Four patients met the comprehensive diagnostic criteria for IgG4-RD. The remaining patient lacked data related to the serum IgG4 level. Histologically, a non-specific IP pattern was observed in all patients. The key morphological features of IgG4-RD, such as storiform fibrosis and obliterative phlebitis with lymphoplasmacytic infiltration in a loose background texture, were absent in every patient. In contrast, venule obstruction by densely packed lymphoplasmacytic infiltration was observed in two patients. Marked scarring and remodelling of the lung were also noted, which is not seen typically in IgG4-RD. A favourable response to corticosteroid monotherapy was observed in all patients; however, two patients developed lung cancer during the course of observation. CONCLUSIONS: IP with marked IgG4-positive plasma cell infiltration without extrathoracic lesions of IgG4-RD had different pathological features from those of IgG4-RD, and it is appropriate to regard this as a separate entity.
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Inmunoglobulina G , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/patología , Células Plasmáticas/patología , Anciano , Enfermedades Autoinmunes , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
AIMS: To investigate the pathological features of idiopathic interstitial pneumonia (IIP)-associated pulmonary adenocarcinoma. METHODS AND RESULTS: Surgically resected adenocarcinomas associated with IIP (the IIP group) and adenocarcinomas without IIP (the non-IIP group) were subjected to analysis. Adenocarcinomas in the IIP group were subdivided into two groups: one group included tumours connected to bronchiolar metaplasia in honeycomb lesions (the H-IIP group), and the other included tumours unrelated to honeycomb lesions (the NH-IIP group). Histomorphological appearance and immunohistochemical expression were compared among the H-IIP group, the NH-IIP group, and the non-IIP group. Most of the tumour cells in the H-IIP group had a tall, columnar shape that showed similar features to proximal bronchial epithelium, whereas tumour cells in the NH-IIP group and the non-IIP group had a club-like shape that showed similar features to respiratory bronchiolar/alveolar epithelium. Adenocarcinomas in the H-IIP group tended to be negative for thyroid transcription factor-1 (TTF-1) and positive for hepatocyte nuclear factor-4α (HNF-4α). The frequency of EGFR mutations was significantly lower in adenocarcinomas in the H-IIP group, although the frequencies of KRAS and ALK mutations did not differ among the three groups. CONCLUSIONS: Idiopathic interstitial pneumonia-associated pulmonary adenocarcinomas, especially those arising from honeycomb lesions, have distinct pathological features.
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Adenocarcinoma/patología , Neumonías Intersticiales Idiopáticas/complicaciones , Neoplasias Pulmonares/patología , Adenocarcinoma/complicaciones , Anciano , Anciano de 80 o más Años , Análisis Mutacional de ADN , Supervivencia sin Enfermedad , Receptores ErbB/genética , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Neoplasias Pulmonares/complicaciones , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Proteínas Proto-Oncogénicas p21(ras)/genéticaRESUMEN
BACKGROUND: There have been few data on the chemotherapy in elderly advanced non-small cell lung cancer (NSCLC) patients with poor performance status (PS), and usefulness of chemotherapy for such patients remains unclear. The objective of this study was to identify factors that predicted the survival benefit of chemotherapy. METHODS: All consecutive elderly patients (≥75 years) with advanced NSCLC, Eastern Cooperative Oncology Group PS ≥2, EGFR mutation wild type/unknown, and newly diagnosed from January 2009 to December 2012 at a tertiary hospital were retrospectively reviewed. RESULTS: We enrolled 59 patients, and 31 patients received at least one chemotherapy regimen (chemotherapy group). However, 28 patients received best supportive care (BSC) alone (BSC group). The proportion of PS 2 and serum albumin levels was significantly higher in the chemotherapy group than in the BSC group. In the chemotherapy group, log-rank testing did not show statistically significant differences in overall survival (OS) between the single-agent therapy group and carboplatin-based doublet therapy group; however, the OS of patients receiving chemotherapy for only 1 cycle (early termination) was significantly shorter than patients receiving chemotherapy for ≥2 cycles. Hypoalbuminemia was not only a risk factor for the early termination of chemotherapy but also an independent prognostic factor in the chemotherapy group. A receiver operating characteristic curve analysis showed that the best cut-off value was 3.40 g/dL. In patients with serum albumin levels ≥3.40 g/dL, OS was significantly better in the chemotherapy group than in the BSC group (p = 0.0156), however, patients with serum albumin levels <3.40 g/dL exhibited poor prognosis regardless of the presence or absence of chemotherapy. CONCLUSION: In the elderly NSCLC patients with poor PS, serum albumin levels may help identify certain patient populations more likely to receive a survival benefit of systemic chemotherapy.
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Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Albúmina Sérica/metabolismo , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Cisplatino/uso terapéutico , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Curva ROC , Estudios Retrospectivos , Análisis de Supervivencia , Centros de Atención Terciaria , Resultado del TratamientoRESUMEN
We herein analyzed the relationships among the immunohistochemical expression of alpha-enolase (ENO1) and clinicopathological factors in order to define the significance of ENO1 in lung adenocarcinomas (ADCs). ENO1 expression was detected in most of the ADCs examined (95.8%), but not in bronchial and alveolar epithelia. ENO1 expression was typically observed in the cytoplasm among most ADCs (95.8%), but was also detected in the nucleus (56.3%). The levels were significantly higher in terminal respiratory unit (TRU) cytological subtype ADCs. Neither cytoplasmic nor nuclear expression was associated with any other clinicopathological factors including post-operative survival and growth activity. These results suggest that ENO1 is a crucial factor promoting neoplastic transformation exclusively in TRU subtype ADCs. We also investigated the potential utility of the immunohistochemical expression of ENO1 to differentiate TRU-type ADC cells from the reactive hyperplasia of pneumocytes and bronchiolar epithelial cells because difficulties are associated with discriminating these lesions in small biopsy specimens. The sensitivity and specificity of ENO1 (cytoplasmic/nuclear) were 87.5%/37.5% and 88.9%/100%, respectively, which are superior to those of p53 (18.8% and 100%). ENO1 has potential as a biomarker to assist in the histopathological detection of TRU subtype ADC cells.