RESUMEN
BACKGROUND: Interstitial lung abnormalities (ILAs) are subtle or mild parenchymal abnormalities observed in more than 5% of the lungs on computed tomography (CT) scans in patients in whom interstitial lung disease was not previously clinically suspected and is considered. ILA is considered to be partly undeveloped stages of idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF). This study aims to clarify the frequency of subsequent IPF or PPF diagnosis, the natural course from the preclinical status of the diseases, and the course after commencing treatment. METHODS: This is an ongoing, prospective, multicentre observational cohort study of patients with ILA referred from general health screening facilities with more than 70,000 annual attendances. Up to 500 participants will be enrolled annually over 3 years, with 5-year assessments every six months. Treatment intervention including anti-fibrotic agents will be introduced in disease progression cases. The primary outcome is the frequency of subsequent IPF or PPF diagnoses. Additionally, secondary and further endpoints are associated with the efficacy of early therapeutic interventions in cases involving disease progression, including quantitative assessment by artificial intelligence. DISCUSSION: This is the first prospective, multicentre, observational study to clarify (i) the aetiological data of patients with ILA from the largest general health check-up population, (ii) the natural course of IPF or PPF from the asymptomatic stage, and (iii) the effects and outcomes of early therapeutic intervention including anti-fibrotic agents for progressive cases of ILA. The results of this study could significantly impact the clinical practice and treatment strategy for progressive fibrosing interstitial lung diseases. TRIAL REGISTRATION NUMBER: UMIN000045149.
Asunto(s)
Fibrosis Pulmonar Idiopática , Enfermedades Pulmonares Intersticiales , Humanos , Japón , Antifibróticos , Inteligencia Artificial , Pueblos del Este de Asia , Estudios Prospectivos , Pulmón/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/epidemiología , Fibrosis Pulmonar Idiopática/diagnóstico por imagen , Fibrosis Pulmonar Idiopática/complicaciones , Estudios de Cohortes , Progresión de la EnfermedadRESUMEN
BACKGROUND: There is no existing reliable and practical method for predicting the prognosis of acute respiratory distress syndrome (ARDS). OBJECTIVE: We aimed to clarify the association between the ROX index, which is calculated as the ratio of peripheral oxygen saturation divided by the fraction of inspired oxygen to the respiratory rate, and the prognosis of patients with ARDS under ventilator support. METHODS: In this single-center retrospective cohort study from prospectively collected database, eligible patients were categorized into three groups based on ROX tertiles. The primary outcome was the 28-day survival, and the secondary outcome was 28-day liberation from ventilator support. We performed multivariable analysis using the Cox proportional hazards model. RESULTS: Among 93 eligible patients, 24 (26%) patients died. The patients were divided into three groups according to the ROX index (< 7.4, 7.4-11, ≥ 11), with 13, 7, and 4 patients dying in the groups, respectively. A higher ROX index was associated with lower mortality; adjusted hazard ratios [95% CIs] for increasing tertiles of ROX index: 1[reference], 0.54[0.21-1.41], 0.23[0.074-0.72] (P = 0.011 for trend) and a higher rate of successful 28-day liberation from ventilator support; adjusted hazard ratios [95% CIs] for increasing tertiles of ROX index: 1[reference], 1.41[0.68-2.94], 2.80[1.42-5.52] (P = 0.001 for trend). CONCLUSIONS: The ROX index at 24 h after initiating ventilator support is a predictor of outcomes in patients with ARDS and might inform initiation of more advanced treatments.
Asunto(s)
Síndrome de Dificultad Respiratoria , Frecuencia Respiratoria , Humanos , Pronóstico , Estudios Retrospectivos , Síndrome de Dificultad Respiratoria/diagnóstico , Síndrome de Dificultad Respiratoria/terapia , CogniciónRESUMEN
There have been no report of objective clinical characteristics or prognostic factors that predict fatal outcome of acute respiratory distress syndrome (ARDS) since the Berlin definition was published. The aim of this study is to identify clinically available predictors that distinguish between two phenotypes of fatal ARDS due to pneumonia. In total, 104 cases of Japanese patients with pneumonia-induced ARDS were extracted from our prospectively collected database. Fatal cases were divided into early (< 7 days after diagnosis) and late (≥ 7 days) death groups, and clinical variables and prognostic factors were statistically evaluated. Of the 50 patients who died within 180 days, 18 (36%) and 32 (64%) were in the early (median 2 days, IQR [1, 5]) and late (median 16 days, IQR [13, 29]) death groups, respectively. According to multivariate regression analyses, the APACHE II score (HR 1.25, 95%CI 1.12-1.39, p < 0.001) and the disseminated intravascular coagulation score (HR 1.54, 95%CI 1.15-2.04, p = 0.003) were independent prognostic factors for early death. In contrast, late death was associated with high-resolution computed tomography (HRCT) score indicating early fibroproliferation (HR 1.28, 95%CI 1.13-1.42, p < 0.001) as well as the disseminated intravascular coagulation score (HR 1.24, 95%CI 1.01-1.52, p = 0.039). The extent of fibroproliferation on HRCT, and the APACHE II scores along with coagulation abnormalities, should be considered for use in predictive enrichment and personalized medicine for patients with ARDS due to pneumonia.
Asunto(s)
APACHE , Infecciones/fisiopatología , Fenotipo , Neumonía/complicaciones , Síndrome de Dificultad Respiratoria/mortalidad , Síndrome de Dificultad Respiratoria/patología , Tomografía Computarizada por Rayos X/métodos , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Unidades de Cuidados Intensivos , Masculino , Pronóstico , Estudios Prospectivos , Curva ROC , Síndrome de Dificultad Respiratoria/diagnóstico por imagen , Síndrome de Dificultad Respiratoria/etiología , Estudios Retrospectivos , Tasa de SupervivenciaAsunto(s)
Antibacterianos/uso terapéutico , Antifibróticos/uso terapéutico , Antitusígenos/uso terapéutico , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Polifarmacia , Piridonas/uso terapéutico , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease course. The recent advancement of antifibrotic therapy has increased the need for reliable and specific biomarkers. This study aimed to assess alveolar epithelial biomarkers as predictors for the efficacy of the antifibrotic drug pirfenidone. METHODS: We conducted a post-hoc analysis of the prospective, multicenter, randomized, placebo-controlled, phase 3 trial of pirfenidone in Japan (total, n = 267; pirfenidone, n = 163; placebo, n = 104). Logistic regression analysis was performed to extract parameters that predicted disease progression, defined by a ≥ 10% relative decline in vital capacity (VC) from baseline and/or death, at week 52. For assessment of serum surfactant protein (SP)-D, SP-A and Krebs von den Lungen (KL)-6, all patients were dichotomized by the median concentration of each biomarker at baseline to the high and low biomarker subgroups. Associations of these concentrations were examined with changes in VC at each time point from baseline up to week 52, along with progression-free survival (PFS). Additionally, the effect of pirfenidone treatment on serial longitudinal concentrations of these biomarkers were evaluated. RESULTS: In the multivariate logistic regression analysis, body mass index (BMI), %VC and SP-D in the pirfenidone group, and BMI and %VC in the placebo group were indicated as predictors of disease progression. Pirfenidone treatment reduced the decline in VC with statistical significance in the low SP-D and low SP-A subgroups over most of the treatment period, and also prolonged PFS in the low SP-D and low KL-6 subgroups. Furthermore, SP-D levels over time course were reduced in the pirfenidone group from as early as week 8 until the 52-week treatment period compared with the placebo group. CONCLUSIONS: Serum SP-D was the most consistent biomarker for the efficacy of pirfenidone in the cohort trial of IPF. Serial measurements of SP-D might have a potential for application as a pharmacodynamic biomarker. Trial registration The clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC) on September 13, 2005 (registration No. JapicCTI-050121; http://Clinicaltrials.jp ).
Asunto(s)
Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Pulmón/efectos de los fármacos , Proteína D Asociada a Surfactante Pulmonar/sangre , Piridonas/uso terapéutico , Anciano , Biomarcadores/sangre , Índice de Masa Corporal , Método Doble Ciego , Femenino , Humanos , Fibrosis Pulmonar Idiopática/sangre , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/fisiopatología , Pulmón/metabolismo , Pulmón/patología , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Piridonas/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Capacidad VitalRESUMEN
Recent studies have suggested that an increased peripheral monocyte count predicts a poor outcome in fibrosing interstitial lung disease (ILD). However, the association between an increased monocyte count and acute exacerbations (AEs) of fibrosing ILD remains to be elucidated. Our retrospective cohort study aimed to assess the impact of peripheral monocyte count on AEs of fibrosing ILD. We analyzed the electronic medical records of 122 consecutive patients with fibrosing ILD and no prior history of an AE, who were treated with anti-fibrotic agents from August 2015 to December 2018. We determined their peripheral monocyte counts at anti-fibrotic agent initiation and performed univariate and multivariate Cox regression analyses of time-to-first AE after anti-fibrotic agent initiation to assess the impact of monocyte count on AEs of fibrosing ILD. Twenty-six patients developed an AE during the follow-up period, and there was an increased monocyte count at anti-fibrotic agent initiation in these patients compared to those who did not develop an AE. There was also a significantly shorter time-to-first AE of fibrosing ILD in patients with a higher absolute monocyte count. Subgroup analyses indicated similar results regardless of the idiopathic pulmonary fibrosis diagnoses. This association was independently significant after adjusting for the severity of the fibrosing ILD. Using our results, we developed a simple scoring system consisting of two factors-monocyte count (<>380 µL-1) and ILD-gender, age, physiology score (<>4 points). Our findings suggest that the absolute monocyte count is an independent significant risk factor for AE in patients with fibrosing ILD. Our simple scoring system may be a predictor for AEs of fibrosing ILD, although further studies are needed to verify our findings.
Asunto(s)
Fibrosis Pulmonar Idiopática , Recuento de Leucocitos , Monocitos , Brote de los Síntomas , Progresión de la Enfermedad , Registros Electrónicos de Salud/estadística & datos numéricos , Femenino , Humanos , Fibrosis Pulmonar Idiopática/sangre , Fibrosis Pulmonar Idiopática/epidemiología , Fibrosis Pulmonar Idiopática/fisiopatología , Fibrosis Pulmonar Idiopática/terapia , Japón/epidemiología , Recuento de Leucocitos/métodos , Recuento de Leucocitos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Pruebas de Función Respiratoria , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
Drugs can cause acute respiratory distress syndrome (ARDS). However, there is no established clinical prediction rule for drug-associated ARDS (DARDS). We aimed to develop and validate a scoring system for DARDS prediction. We analysed data collected from a prospective, single-centre, cohort study that included ARDS patients. The ARDS diagnosis was based on the American-European Consensus Conference or Berlin definition. Drug-associated acute lung injury (DALI) was defined as previous exposure to drugs which cause ALI and presence of traditional risk factors for ALI. High-resolution computed tomography (HRCT; indicating extent of lung damage with fibroproliferation), Acute Physiology and Chronic Health Evaluation (APACHE) II, and disseminated intravascular coagulation (DIC; indicating multiorgan failure) scores and PaO2/FiO2 were evaluated for their ability to predict DARDS. Twenty-nine of 229 patients had DARDS. The HRCT, APACHE II, and DIC scores and PaO2/FiO2 were assessed. The model-based predicted probability of DARDS fitted well with the observed data, and discrimination ability, assessed through bootstrap with an area under the receiver-operating curve, improved from 0.816 to 0.875 by adding the HRCT score. A simple clinical scoring system consisting of the APACHE II score, PaO2/FiO2, and DIC and HRCT scores can predict DARDS. This model may facilitate more appropriate clinical decision-making.
Asunto(s)
Síndrome de Dificultad Respiratoria/inducido químicamente , Síndrome de Dificultad Respiratoria/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Anciano , Área Bajo la Curva , Femenino , Humanos , Modelos Logísticos , Masculino , Análisis Multivariante , Curva ROC , Síndrome de Dificultad Respiratoria/diagnósticoRESUMEN
BACKGROUND AND OBJECTIVE: Here, we present real-world data on the incidence and risk factors of acute exacerbation (AE) in patients with chronic fibrotic interstitial pneumonia (CFIP) treated with antifibrotic agents, which has been previously poorly documented. METHODS: We retrospectively examined clinical characteristics, incidence and risk factors of AE in a cohort of 100 patients with CFIP (n = 75, idiopathic pulmonary fibrosis [IPF]; n = 25, other conditions), all of whom received antifibrotic agents in a real-world setting. RESULTS: The median follow-up was 17.4 months (interquartile range [IQR], 6.6 to 26.7 months). During the follow-up periods, 21 patients experienced AE after starting antifibrotic agents. The estimated 1-, 2-, and 3-year AE incidence rates were 11.4% (95% confidence interval [95%CI], 6.2-20.3%), 32% (95%CI, 20.7-47.4%), and 36.3% (95%CI 23.5-53.1%), respectively. Decreased baseline lung function (forced vital capacity and carbon monoxide diffusing capacity of the lung), existence of pulmonary hypertension estimated from an echocardiogram, higher Interstitial Lung Disease-Gender, Age, and Physiology (ILD-GAP) score, supplementary oxygen, and concomitant corticosteroid and proton-pump inhibitor (PPI) use upon starting the antifibrotic agent were risk factors of AE. Concomitant corticosteroid and PPI use and corticosteroid dose were risk factor of AE in a multivariate Cox regression hazard model adjusting for ILD-GAP score. CONCLUSION: AE of CFIP is more common in patients with physiologically and functionally advanced disease under antifibrotic agents. Prudent use of corticosteroids and PPIs when initiating antifibrotic agents may be recommended. Further studies are warranted.
Asunto(s)
Progresión de la Enfermedad , Fibrosis Pulmonar Idiopática/diagnóstico , Pulmón/fisiopatología , Capacidad Vital , Enfermedad Aguda , Corticoesteroides/uso terapéutico , Anciano , Femenino , Humanos , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/fisiopatología , Incidencia , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Inhibidores de la Bomba de Protones/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Although acute respiratory distress syndrome (ARDS) reportedly shows various clinical phenotypes with different risk and prognostic factors, few studies have assessed the clinical features and prognosis of pulmonary and extrapulmonary ARDS. The aim of the present study was to investigate clinical differences between pulmonary and extrapulmonary ARDS. METHODS: In total, 200 patients who met the Berlin criteria and were diagnosed with ARDS between October 2004 and September 2017 were included. We classified the patients into pulmonary and extrapulmonary ARDS groups. Both groups were assessed for 60-day mortality, duration of ventilation, and other clinical features. RESULTS: There were 150 and 50 patients in the pulmonary and extrapulmonary ARDS groups, respectively. The two groups showed no significant differences in any assessment parameters except the serum lactate dehydrogenase (LDH) level, which was higher in the extrapulmonary ARDS group (P=0.01). After adjustment for potentially confounding covariates, there were no significant differences in 60-day mortality (P=0.99) and the duration of ventilation (P=0.45) between the two groups. Mortality was significantly associated with the disseminated intravascular coagulation (DIC) score, high-resolution computed tomography (HRCT) score, and serum LDH level in the pulmonary ARDS group and the DIC score and HRCT score in the extrapulmonary ARDS group. CONCLUSIONS: Pulmonary and extrapulmonary ARDS may be comparable in terms of the prognosis and duration of ventilation. DIC and HRCT scores may be common clinical predictors of mortality with ARDS.
RESUMEN
Effective pharmacological therapy has not been established for patients with acute respiratory distress syndrome (ARDS). Macrolides are antibiotics with potent immunomodulatory and anti-inflammatory effects that may be beneficial in ARDS treatment. The objective of this study was to determine the adjunctive effect of azithromycin on survival for patients with ARDS. This single-center, retrospective cohort evaluation of hospitalized patients with moderate or severe ARDS was conducted to assess the impact of intravenous azithromycin on clinical outcomes using a propensity score analysis. All data were collected prospectively as part of ongoing research on the utility of high-resolution computed tomography in ARDS. The primary outcome was 90-day mortality, and the secondary analysis assessed the effect of azithromycin on time to successful discontinuation of mechanical ventilation and 28-day mortality. Of 191 eligible patients with severe or moderate ARDS, 62 were treated with azithromycin. The 62 patients treated with azithromycin and 62 not treated with azithromycin were matched and analysed. Azithromycin use was associated with a statistically significant improvement in 90-day survival rate (Hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.27-0.87; P = 0.015) and a shorter time to successful discontinuation of mechanical ventilation (HR, 1.74; 95% CI, 1.07-2.81; P = 0.026). The 28-day mortality rate tended to be higher in the azithromycin cohort than in the non-azithromycin cohort, but this was not statistically significant. Adjunctive intravenous azithromycin therapy was effective in patients with moderate or severe ARDS. Further prospective randomized controlled trials are needed to confirm this result.
Asunto(s)
Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Síndrome Respiratorio Agudo Grave/tratamiento farmacológico , Síndrome Respiratorio Agudo Grave/mortalidad , Anciano , Anciano de 80 o más Años , Femenino , Mortalidad Hospitalaria , Humanos , Pulmón/patología , Masculino , Neumonía/tratamiento farmacológico , Neumonía/microbiología , Puntaje de Propensión , Estudios Prospectivos , Respiración Artificial/estadística & datos numéricos , Estudios RetrospectivosRESUMEN
OBJECTIVES: To report the clinical features and prognosis of drug-associatedacute respiratory distress syndrome (ARDS). DESIGN: A retrospective analysis of data collected during a prospective cohort study. SETTING: Intensive care unit in a teaching hospital. PARTICIPANTS: A total of 197 Japanese patients with ARDS diagnosed by the Berlin definition who were admitted to the Division of Respiratory Medicine from October 2004 to December 2015 were enrolled in the study and were classified as two groups according to their causes: a drug-associated ARDS group (n=27) and a non-drug-associated ARDS group (n=170). Primary outcome measure is 28-day mortality, and the secondaryoutcome measure is ventilator-free days. RESULTS: The Acute Physiology and Chronic Health Evaluation II scores were significantly lower in the drug-associated ARDS group than in the non-drug-associated ARDS group (median (IQR): 18.0 (16.5-21.0) vs 23.0 (18.0-26.0), p<0.001), and the arterial oxygen tension/fractional inspired oxygen ratio was higher (148.0 (114.1-177.5) vs 101.0 (71.5-134.0), p=0.003). In the drug-associated ARDS group, although high-resolution CT scores indicative of the extent of fibroproliferation (301.6 (244.1-339.8) vs 208.3 (183.4-271.6), p<0.001), serum lactate dehydrogenase levels (477 (365-585) vs 322 (246-434), p=0.003) and the McCabe scores (score 1/2/3, n (%): 20 (74)/4 (15)/3 (11)vs154 (91)/7 (4)/9 (5), p=0.04) were significantly higher, ventilator weaning was earlier (p<0.001) and 28-day mortality was better (p=0.043). After adjusting for potentially confounding covariates, drug-associated ARDS group was associated with lower 28-day mortality (adjusted HR (HR) 0.275; 95% CI 0.106 to 0.711; p=0.008). CONCLUSIONS: Although more severe lung damage with fibroproliferation was observed in patients with drug-associated ARDS, ventilator weaning was earlier, and their prognosis was better than the others. Further well-designed prospective studies are needed.
Asunto(s)
Síndrome de Dificultad Respiratoria/inducido químicamente , Síndrome de Dificultad Respiratoria/mortalidad , Desconexión del Ventilador , Anciano , Anciano de 80 o más Años , Análisis de los Gases de la Sangre , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Japón , L-Lactato Deshidrogenasa/sangre , Pulmón/fisiopatología , Masculino , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is a fatal condition without an established pharmaceutical treatment. Most patients are treated with high-dose corticosteroids and broad-spectrum antibiotics. Azithromycin is a macrolide with immunomodulatory activity and may be beneficial for treatment of acute lung injury. The objective of this study was to determine the effect of azithromycin on survival of patients with idiopathic AE of IPF. METHODS: We evaluated 85 consecutive patients hospitalized in our department for idiopathic AE of IPF from April 2005 to August 2016. The initial 47 patients were treated with a fluoroquinolone-based regimen (control group), and the following 38 consecutive patients were treated with azithromycin (500 mg/day) for 5 days. Idiopathic AE of IPF was defined using the criteria established by the 2016 International Working Group. RESULTS: Mortality in patients treated with azithromycin was significantly lower than in those treated with fluoroquinolones (azithromycin, 26% vs. control, 70%; p < 0.001). Multivariate analysis revealed that the two variables were independently correlated with 60-day mortality as determined by the Acute Physiology and Chronic Health Evaluation II score (p = 0.002) and azithromycin use (p < 0.001). CONCLUSION: Azithromycin may improve survival in patients with idiopathic AE of IPF.
Asunto(s)
Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , APACHE , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Fluoroquinolonas/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Brote de los SíntomasRESUMEN
BACKGROUND: The efficacy of corticosteroid use in acute respiratory distress syndrome (ARDS) remains controversial. Generally, short-term high-dose corticosteroid therapy is considered to be ineffective in ARDS. On the other hand, low-dose, long-term use of corticosteroids has been reported to be effective since they provide continued inhibition of the systemic inflammatory response syndrome (SIRS) that accompanies ARDS. Thus far, no reports have been published on the efficacy of initiating treatment with a high-dose corticosteroid regimen with tapering. METHODS: We conducted a retrospective observational study involving 186 patients treated at a teaching hospital (68% had sepsis, pneumonia, or aspiration pneumonia). ARDS was diagnosed according to the Berlin definition. Patients were divided into a high-dose (n = 21) or low-dose corticosteroid group (n = 165) to compare the effectiveness of a down-titration regimen. The primary medical team chose which treatment a patient would receive. We were careful to conduct a differential diagnosis of interstitial pneumonia (e.g., acute eosinophilic pneumonia) since corticosteroid treatment has been proven effective in that patient population. The primary outcome was the 60-day mortality rate. The secondary outcome was the number of ventilator-free days (VFD). RESULTS: Those started on a high-dose regimen had a significantly higher 60-day mortality rate (P = 0.031) with significantly fewer VFD (P = 0.021). Propensity scores were used to adjust patient backgrounds in a variable analysis that also showed the high-dose regimen was a factor in decreasing VFD (OR, 95.63; 95% CI, 1.74-5271.07; P = 0.026) and worsening the 60-day mortality rate (OR, 2.54; 95% CI, 0.92-7.02; P = 0.072). CONCLUSIONS: A tapering regimen after high-dose corticosteroids is likely to increase ventilator dependency and might aggravate the prognosis of patients with ARDS diagnosed according to the Berlin definition.
Asunto(s)
Metilprednisolona/administración & dosificación , Metilprednisolona/farmacología , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , APACHE , Corticoesteroides/administración & dosificación , Corticoesteroides/farmacología , Corticoesteroides/uso terapéutico , Anciano , Berlin , Femenino , Humanos , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Puntuaciones en la Disfunción de Órganos , Pronóstico , Puntaje de Propensión , Síndrome de Dificultad Respiratoria/mortalidad , Estudios RetrospectivosRESUMEN
PURPOSE: Acute respiratory distress syndrome is a life-threatening form of respiratory failure without an established pharmacological treatment. Recently, macrolides have been found to be beneficial in cases of acute lung injury, but evidence is limited. MATERIALS AND METHODS: This single-centre retrospective cohort evaluation of hospitalized patients with sepsis-associated acute respiratory distress syndrome aimed to assess the impact of azithromycin on clinical outcomes by using a propensity score analysis. All data were collected prospectively as part of ongoing research on high-resolution computed tomography of acute respiratory distress syndrome. The primary outcome was 60-day mortality; the secondary outcome was the number of ventilator-free days. RESULTS: Twenty-nine of 125 patients with sepsis-associated acute respiratory distress syndrome (23.2 %) received azithromycin within 24 h after acute respiratory distress syndrome diagnosis. After adjusting for potentially confounding covariates, azithromycin use was associated with lower 60-day mortality (hazard ratio, 0.31; 95 % confidence interval, 0.11-082; P = 0.02) and a shorter time to successful discontinuation of mechanical ventilation. CONCLUSIONS: Azithromycin use was associated with decreased mortality and ventilator dependency in patients with sepsis-associated acute respiratory distress syndrome. Further well-designed prospective studies are needed.
RESUMEN
BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a lifethreatening event and one of the important endpoints in clinical trials involving IPF. Despite this, there has been little evaluation of the potential risk factors for AE-IPF in clinical trials. We evaluated the risk factors for AE-IPF in a phase III clinical trial of pirfenidone in Japanese IPF patients. METHODS: The study population comprised 267 patients. The effects of various baseline characteristics as possible risk factors for AE-IPF during the study, as well as those of a ≥10% decline in percent vital capacity (%VC) within 6 months, were evaluated using Cox׳s proportional hazard model. The ≥10% decline in %VC was calculated in two ways: (1) an absolute decline (e.g. from 60% predicted to 50%); and (2) a relative decline (e.g. from 60% predicted to 54%). RESULTS: Over 52 weeks, 14 patients experienced AE-IPF. Univariate analysis using Cox׳s proportional hazards model showed that both relative and absolute ≥10% decline in %VC within 6 months were significant risk factors for AE-IPF. Stepwise multivariate analysis demonstrated that absolute or relative decline in both %VC and alveolar to arterial oxygen pressure difference (AaDO2) were significant risk factors for AE. The model using absolute decline [Hazard Ration (HR)=7.405, p=0.0007] and baseline AaDO2 (HR=1.063, p=0.0266) had a better fit than the model using relative decline and baseline AaDO2. CONCLUSIONS: Rapid %VC decline (≥10% within 6 months), and high baseline AaDO2, may be risk factors for AE-IPF.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Piridonas/uso terapéutico , Enfermedad Aguda , Adulto , Anciano , Ensayos Clínicos Fase III como Asunto , Progresión de la Enfermedad , Femenino , Humanos , Fibrosis Pulmonar Idiopática/fisiopatología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Consumo de Oxígeno , Modelos de Riesgos Proporcionales , Alveolos Pulmonares/metabolismo , Factores de Riesgo , Capacidad VitalRESUMEN
BACKGROUND: A phase III clinical trial of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) in Japan has revealed that pirfenidone attenuated the decline in vital capacity (VC) and improved progression-free survival (PFS). We conducted an extended analysis of the pirfenidone trial to investigate its efficacy with respect to IPF severity in the trial population. METHODS: Patients in the phase III trial were stratified by baseline pulmonary functions including %VC predicted, %diffusion capacity for carbon monoxide predicted, and oxygen saturation by pulse oximetry on exertion and were categorized into mild, moderate, and severe groups of functional impairment. The efficacy of pirfenidone for VC and PFS over 52 weeks was compared among the three sub-populations. RESULTS: Of 264 patients, 102 (39%), 90 (34%), and 72 patients (27%) were classified as having mild, moderate, and severe grades of functional impairment, respectively. This classification was associated with arterial oxygen partial pressure at rest and degree of dyspnea at baseline. While pirfenidone attenuated VC decline at all grades of severity, covariance analysis revealed pirfenidone to have better efficacy in the sub-population with mild-grade IPF. Mixed model repeated measures analysis confirmed that pirfenidone markedly attenuated VC decline in patients with mild-grade IPF compared to its effects in patients with moderate or severe IPF. Pirfenidone also improved PFS markedly in patients with mild-grade IPF. CONCLUSION: This extended analysis suggested that pirfenidone exerted better therapeutic effects in patients with milder IPF. Further analysis with a larger population is needed to confirm these results.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Ensayos Clínicos Fase III como Asunto , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Piridonas/uso terapéutico , Adulto , Anciano , Femenino , Humanos , Fibrosis Pulmonar Idiopática/mortalidad , Fibrosis Pulmonar Idiopática/fisiopatología , Masculino , Persona de Mediana Edad , Consumo de Oxígeno , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Resultado del Tratamiento , Capacidad Vital , Adulto JovenRESUMEN
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease with a median survival of 2-5 years and limited treatment options. In 2008, pirfenidone became the first drug to be approved for IPF treatment in Japan. The aim of this study was to assess the safety of pirfenidone for IPF treatment in a clinical setting. METHODS: We conducted a safety-oriented post-marketing surveillance of all patients with IPF who were administered pirfenidone in the first year after its launch in Japan. This was a prospective, non-interventional, observational study. Case report forms were used to collect survey data, comprising adverse events, acute exacerbations, patient demographics, concomitant drug use, and concurrent treatment data. RESULTS: Of the 1371 patients available for safety evaluation, two-thirds had stage III-IV disease. The incidence of total adverse drug reactions (ADRs) was 64.6%. ADRs with an incidence of ≥3% were decreased appetite, photosensitivity reaction, nausea, abdominal discomfort, malaise, somnolence, and hepatic function abnormal. This safety profile was consistent with the findings in phase II and III trials in Japan. The discontinuation rates due to adverse events at 12 months for each disease stage were similar; however, discontinuation caused by disease progression increased with disease severity. Treatment with pirfenidone stabilized both vital capacity and subjective symptoms in most patients (70-80%) treated for at least 6 months. CONCLUSIONS: This post-marketing surveillance in Japan showed that pirfenidone was generally well tolerated in patients with IPF, including those with severe lung function impairment.
Asunto(s)
Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Vigilancia de Productos Comercializados , Piridonas/uso terapéutico , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Fibrosis Pulmonar Idiopática/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Piridonas/efectos adversos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Capacidad VitalRESUMEN
BACKGROUND: Acute exacerbation of chronic fibrosing interstitial pneumonia (AE-CFIP) is an often fatal condition with no established treatment. Recently, macrolides were found to be beneficial in cases of acute lung injury. OBJECTIVES: To examine the clinical effectiveness and safety of intravenous azithromycin in patients hospitalized for AE-CFIP. METHODS: A prospective, open-label study with historical controls was conducted. Twenty consecutive patients with AE-CFIP received azithromycin. They were compared with a historical cohort treated with fluoroquinolone (n = 56). All patients received high-dose steroid pulse therapy. The primary end point was mortality at 60 days. The secondary end point was safety of intravenous azithromycin in patients with AE-CFIP. Inverse probability of treatment weighting (IPTW) using the propensity score was performed to investigate the relationship between azithromycin use and survival time. RESULTS: Mortality was significantly lower in the patients treated with azithromycin than in those treated with fluoroquinolone (mortality rate at 60 days: 20 vs. 69.6%, p < 0.001; median survival time: not reached vs. 29.5 days, p < 0.001). The IPTW adjusted hazard of mortality at 60 days in patients receiving azithromycin was 0.17 (95% CI 0.05-0.61). No serious adverse events were observed. CONCLUSIONS: Azithromycin was associated with improved outcomes in patients with AE-CFIP. Further studies are needed to verify this finding (Clinical trial JMA-IIA00095).
Asunto(s)
Azitromicina , Fluoroquinolonas , Enfermedades Pulmonares Intersticiales , Esteroides , Administración Intravenosa , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Azitromicina/administración & dosificación , Azitromicina/efectos adversos , Enfermedad Crónica , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Monitoreo de Drogas , Quimioterapia Combinada/métodos , Femenino , Fluoroquinolonas/administración & dosificación , Fluoroquinolonas/efectos adversos , Humanos , Japón/epidemiología , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/mortalidad , Enfermedades Pulmonares Intersticiales/fisiopatología , Masculino , Estudios Prospectivos , Esteroides/administración & dosificación , Esteroides/efectos adversos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Human T-cell leukemia virus type 1 (HTLV-1) carriers are rarely subject to inflammatory disorders in multiple organs, other than the well-known complication, adult T-cell leukemia/lymphoma (ATLL). HTLV-1 associated bronchiolo-alveolar disorder (HABA) has been proposed as an immune mediated pulmonary reaction seen rarely in HTLV-1 carriers. The reported clinico-pathological patterns of HABA are diffuse panbronchiolitis (DPB) and lymphoid interstitial pneumonia (LIP). We here report three cases of HTLV-1 carriers showing miliary micro-nodules throughout both lungs. Microscopic examination in the video assisted thoracic surgery biopsies demonstrated that all cases had multiple discrete micro-nodules which consisted of marked lymphoid infiltration, granulomas, eosinophils and a few foci of necrosis inside the granuloma. No findings indicating ATLL, other neoplastic conditions, infection or interstitial pneumonia, including DPB and LIP, were present following panels of special staining and immunohistochemical examinations. Two patients improved without treatment within one month, with no evidence of recurrence after 7 years. One patient showed slow deterioration of lung reticular shadows in spite of a low dose corticosteroid therapy (prednisolone 10 mg/day). We believe these cases may be a newly recognized variant of HABA.
Asunto(s)
Infecciones por Deltaretrovirus/complicaciones , Infecciones por Deltaretrovirus/patología , Enfermedades Pulmonares/patología , Enfermedades Pulmonares/virología , Anciano , Virus Linfotrópico T Tipo 1 Humano , Humanos , MasculinoRESUMEN
Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, bleeding tendency, and lysosomal accumulation of ceroid-like material, with occasional development of interstitial pneumonia (IP). Nine genetically distinct subtypes of HPS are known in humans; IP develops primarily in types 1 and 4. Most reported cases of HPS with IP are type 1, and there are no published reports of type 4 in Japanese individuals. A 58-year-old man with congenital oculocutaneous albinism and progressive dyspnea for 1 month was admitted to our hospital. We administered high-dose corticosteroids on the basis of a diagnosis of acute exacerbation of interstitial pneumonia. Respiratory symptoms and the findings of high-resolution computed tomography (CT) showed improvement. He was diagnosed with HPS type 4 with interstitial pneumonia on the basis of gene analysis. He has been receiving pirfenidone for 1 year and his condition is stable. This is the first report on the use of pirfenidone for HPS with IP caused by a novel mutation in the HPS4 gene. We conclude that HPS should be suspected in patients with albinism and interstitial pneumonia. High-dose corticosteroid treatment may be useful in cases of acute exacerbation of interstitial pneumonia due to HPS-4, and pirfenidone may be useful and well tolerated in patients with HPS-4.