RESUMEN
BACKGROUND: Acute exacerbation of fibrosing interstitial lung diseases (AE-ILD) is a serious life-threatening event per year. Methylprednisolone and/or immunosuppressive agents (ISA) are a mainstay in any regimen, under the premise that pulmonary infection has been promptly identified and controlled. We investigated the value of bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) on the treatment adjustment of AE-ILD. METHODS: We conducted a cross-sectional observational study. All data were collected prospectively and retrospectively analyzed. We included fifty-six patients with AE-ILD and nineteen stable ILD who underwent BALF mNGS at the beginning of admission. RESULTS: Patients with a variety of ILD classification were included. Connective-tissue disease related ILD (CTD-ILD) occupy the most common underlying non-idiopathic pulmonary fibrosis (non-IPF). The infection-triggered AE accounted for 39.29%, with the majority of cases being mixed infections. The microorganisms load in the AE-ILD group was significantly higher. After adjusted by mNGS, the therapy coverage number of pathogens was significantly higher compared to the initial treatment (p < 0.001). After treatment, the GGO score and the consolidation score were significantly lower during follow up in survivors (1.57 ± 0.53 vs. 2.38 ± 0.83 with p < 0.001, 1.11 ± 0.24 vs. 1.49 ± 0.47 with p < 0.001, respectively). Some detected microorganisms, such as Tropheryma whipplei, Mycobacterium, Aspergillus, and mixed infections were difficult to be fully covered by empirical medication. BALF mNGS was also very helpful for excluding infections and early administration of methylprednisolone and/or ISA. CONCLUSIONS: mNGS has been shown to be a useful tool to determine pathogens in patients with AE-ILD, the results should be fully analyzed. The comprehensive treatment protocol based on mNGS has been shown crucial in AE-ILD patients.
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Líquido del Lavado Bronquioalveolar , Secuenciación de Nucleótidos de Alto Rendimiento , Enfermedades Pulmonares Intersticiales , Humanos , Femenino , Líquido del Lavado Bronquioalveolar/microbiología , Masculino , Persona de Mediana Edad , Anciano , Enfermedades Pulmonares Intersticiales/microbiología , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Estudios Transversales , Estudios Retrospectivos , Inmunosupresores/administración & dosificación , Metagenómica/métodos , Metilprednisolona/administración & dosificación , Progresión de la EnfermedadRESUMEN
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a serious and common extra-articular disease manifestation. Patients with RA-ILD experience reduced bacterial diversity and gut bacteriome alterations. However, the gut mycobiome and virome in these patients have been largely neglected. In this study, we performed whole-metagenome shotgun sequencing on fecal samples from 30 patients with RA-ILD, and 30 with RA-non-ILD, and 40 matched healthy controls. The gut bacteriome and mycobiome were explored using a reference-based approach, while the gut virome was profiled based on a nonredundant viral operational taxonomic unit (vOTU) catalog. The results revealed significant alterations in the gut microbiomes of both RA-ILD and RA-non-ILD groups compared with healthy controls. These alterations encompassed changes in the relative abundances of 351 bacterial species, 65 fungal species, and 4,367 vOTUs. Bacteria such as Bifidobacterium longum, Dorea formicigenerans, and Collinsella aerofaciens were enriched in both patient groups. Ruminococcus gnavus (RA-ILD), Gemmiger formicilis, and Ruminococcus bromii (RA-non-ILD) were uniquely enriched. Conversely, Faecalibacterium prausnitzii, Bacteroides spp., and Roseburia inulinivorans showed depletion in both patient groups. Mycobiome analysis revealed depletion of certain fungi, including Saccharomyces cerevisiae and Candida albicans, in patients with RA compared with healthy subjects. Notably, gut virome alterations were characterized by an increase in Siphoviridae and a decrease in Myoviridae, Microviridae, and Autographiviridae in both patient groups. Hence, multikingdom gut microbial signatures showed promise as diagnostic indicators for both RA-ILD and RA-non-ILD. Overall, this study provides comprehensive insights into the fecal virome, bacteriome, and mycobiome landscapes of RA-ILD and RA-non-ILD gut microbiota, thereby offering potential biomarkers for further mechanistic and clinical research.
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Artritis Reumatoide , Bacterias , Heces , Microbioma Gastrointestinal , Enfermedades Pulmonares Intersticiales , Humanos , Enfermedades Pulmonares Intersticiales/microbiología , Enfermedades Pulmonares Intersticiales/virología , Artritis Reumatoide/complicaciones , Artritis Reumatoide/microbiología , Heces/microbiología , Heces/virología , Femenino , Masculino , Persona de Mediana Edad , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Anciano , Viroma , Micobioma , Adulto , Virus/clasificación , Virus/aislamiento & purificación , Virus/genética , Hongos/aislamiento & purificación , Hongos/clasificaciónRESUMEN
Connective tissue disease-related interstitial lung disease (CTD-ILD) is a frequent and serious complication of CTD, leading to high morbidity and mortality. Unfortunately, its pathogenesis remains poorly understood; however, one intriguing contributing factor may be the microbiome of the mouth and lungs. The oral microbiome, which is a major source of the lung microbiome through recurrent microaspiration, is altered in ILD patients. Moreover, in recent years, several lines of evidence suggest that changes in the oral and lung microbiota modulate the pulmonary immune response and thus may play a role in the pathogenesis of ILDs, including CTD-ILD. Here, we review the existing data demonstrating oral and lung microbiota dysbiosis and possible contributions to the development of CTD-ILD in rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis, and systemic lupus erythematosus. We identify several areas of opportunity for future investigations into the role of the oral and lung microbiota in CTD-ILD.
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Enfermedades del Tejido Conjuntivo , Enfermedades Pulmonares Intersticiales , Pulmón , Microbiota , Boca , Humanos , Enfermedades Pulmonares Intersticiales/microbiología , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades del Tejido Conjuntivo/microbiología , Enfermedades del Tejido Conjuntivo/complicaciones , Boca/microbiología , Pulmón/microbiología , Disbiosis/microbiología , Esclerodermia Sistémica/microbiología , Esclerodermia Sistémica/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/microbiología , Lupus Eritematoso Sistémico/fisiopatologíaRESUMEN
Interstitial Lung Disease (ILD) involves lung disorders marked by chronic inflammation and fibrosis. ILDs include pathologies like idiopathic pulmonary fibrosis (IPF), connective tissue disease-associated ILD (CTD-ILD), hypersensitivity pneumonitis (HP) or sarcoidosis. Existing data covers pathogenesis, diagnosis (especially using high-resolution computed tomography), and treatments like antifibrotic agents. Despite progress, ILD diagnosis and management remains challenging with significant morbidity and mortality. Recent focus is on Progressive Fibrosing ILD (PF-ILD), characterized by worsening symptoms and fibrosis on HRCT. Prevalence is around 30%, excluding IPF, with a poor prognosis. Early diagnosis is crucial for optimizing outcomes in PF-ILD individuals. The lung microbiome comprises all the microorganisms that are in the respiratory tract. Relatively recent research try to evaluate its role in respiratory disease. Healthy lungs have a diverse microbial community. An imbalance in bacterial composition, changes in bacterial metabolic activities, or changes in bacterial distribution within the lung termed dysbiosis is linked to conditions like COPD, asthma and ILDs. We conducted a systematic review of three important scientific data base using a focused search strategy to see how the lung microbiome is involved in the progression of ILDs. Results showed that some differences in the composition and quality of the lung microbiome exist in ILDs that show progressive fibrosing phenotype. The results seem to suggest that the lung microbiota could be involved in ILD progression, but more studies showing its exact pathophysiological mechanisms are needed.
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Enfermedades Pulmonares Intersticiales , Pulmón , Microbiota , Humanos , Enfermedades Pulmonares Intersticiales/microbiología , Pulmón/microbiología , Pulmón/patología , Fibrosis Pulmonar Idiopática/microbiología , Fibrosis Pulmonar Idiopática/patologíaRESUMEN
OBJECTIVES: Non-tuberculous mycobacterial (NTM) lung disease (NTM-LD) prevalence is increasing worldwide. In this study, we aimed to evaluate the clinical significance of NTM pulmonary isolates (NTM-PI) and NTM-LD in patients with systemic autoimmune disease (SAD) who had a concurrent interstitial lung disease (ILD) diagnosis. METHODS: We retrospectively identified patients with SAD who had a concurrent ILD diagnosis (SAD-ILD) and from whom clinically indicated sputum specimens were collected for NTM culture between 2003 and 2018 at a tertiary referral hospital. We analysed the prevalence and risk factors of NTM pulmonary isolates (NTM-PI; ≥1 positive culture) and NTM-LD (≥2 positive cultures). RESULTS: This study included 258 patients. Rheumatoid arthritis and Sjögren's syndrome were the most common SADs (32.2% and 26.7%, respectively). The NTM-negative subgroup had 204 patients (79.1%) and the NTM-PI subgroup had 54 patients (20.9%). In the NTM-PI subgroup, 33 patients had one NTM positive set of specimens (NTM 1+, 12.8% of the entire sample) and 21 had NTM-LD (8.1% of the entire sample). In a multivariable analysis, chronic kidney disease (CKD; adjusted odds ratio [aOR]: 3.10 [1.53, 6.29]) and chronic obstructive pulmonary disease (COPD; aOR: 2.59 [1.16, 5.78]) were significantly associated with NTM-PI. For NTM-LD, CKD (aOR: 2.79 [1.00, 7.76]) and COPD (aOR: 3.70 [1.23, 10.72]) remained significant risk factors. CONCLUSIONS: In patients with SAD-ILD, the NTM-PI and NTM-LD prevalence rates were 20.9% and 8.1%, respectively. COPD and CKD were independent risk factors of both NTM-PI and NTM-LD. Previous use of biological agents was associated with NTM-PI.
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Enfermedades Autoinmunes , Enfermedades Pulmonares Intersticiales , Infecciones por Mycobacterium no Tuberculosas , Humanos , Enfermedades Pulmonares Intersticiales/epidemiología , Enfermedades Pulmonares Intersticiales/microbiología , Enfermedades Pulmonares Intersticiales/diagnóstico , Femenino , Masculino , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Factores de Riesgo , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Anciano , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/microbiología , Enfermedades Autoinmunes/diagnóstico , Micobacterias no Tuberculosas/aislamiento & purificación , Adulto , Esputo/microbiología , Artritis Reumatoide/epidemiología , Artritis Reumatoide/complicacionesRESUMEN
Interstitial lung diseases represent a heterogeneous and wide group of diseases in which factors leading to disease initiation and progression are not fully understood. Recent evidence suggests that the lung microbiome might influence the pathogenesis and progression of interstitial lung diseases. In recent years, the utilization of culture-independent methodologies has allowed the identification of complex and dynamic communities of microbes, in patients with interstitial lung diseases. However, the potential mechanisms by which these changes may drive disease pathogenesis and progression are largely unknown. The aim of this review is to discuss the role of the altered lung microbiome in several interstitial lung diseases. Untangling the host-microbiome interaction in the lung and airway of interstitial lung disease patients is a research priority. Thus, lung dysbiosis is a potentially treatable trait across several interstitial lung diseases, and its proper characterization and treatment might be crucial to change the natural history of these diseases and improve outcomes.
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Bacterias/clasificación , Fibrosis Pulmonar Idiopática/microbiología , Enfermedades Pulmonares Intersticiales/microbiología , Bacterias/aislamiento & purificación , Progresión de la Enfermedad , Humanos , Pulmón/microbiología , MicrobiotaRESUMEN
OBJECTIVE: To investigate the role of bronchoalveolar lavage (BAL) in DM-associated interstitial lung disease (ILD). METHODS: We retrospectively reviewed the medical records of patients with DM-ILD who underwent bronchoscopy between October 2015 and September 2019. We then collated clinical features, laboratory data and bronchoscopy findings. The follow-up study was terminated on the 1 May 2020. RESULTS: A total of 113 DM-ILD patients were included in this study, including 27 patients with acute/subacute interstitial pneumonia (A/SIP) and 86 patients with chronic interstitial pneumonia (CIP). The A/SIP group had significantly lower proportions of lymphocytes and eosinophils in the bronchoalveolar lavage fluid (BALF) than the CIP group, but had a significantly higher proportion of neutrophils. Pathogens were discovered in BALF from 28 (24.8%) patients. Twenty-five (22.1%) patients commenced or changed antibiotic therapy on the basis of their bronchoscopy results. Lymphopenia and intensive care unit care were significantly associated with pathogen-positive BALF findings. Complications of bronchoscopy occurred in nine (8.0%) patients; fever (5.3%) was the most common complication. Twenty-five deaths (25/106, 23.6%) were observed during a mean follow-up of 22 months. Age, A/SIP and anti-MDA5 antibody were identified as independent predictors of a poor outcome, while mechanic's hands was an independent protective factor. However, cellular and pathogen findings in BALF had no significant influence on 30-day or overall mortality. CONCLUSION: Bronchoscopy is a relatively useful instrument to evaluate ILD in patients with DM, and BAL can improve the diagnosis of infection. However, cellular and pathogen findings from BALF had no significant influence on prognosis.
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Lavado Broncoalveolar/estadística & datos numéricos , Broncoscopía/estadística & datos numéricos , Enfermedades Pulmonares Intersticiales/diagnóstico , Adulto , Anciano , Lavado Broncoalveolar/efectos adversos , Broncoscopía/efectos adversos , China/epidemiología , Dermatomiositis/complicaciones , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/microbiología , Enfermedades Pulmonares Intersticiales/mortalidad , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Pulmonary involvement is common in children with scrub typhus. Our paper outlines the clinical characteristics of pulmonary involvement and analyses the predictors of its severity. All scrub typhus serology-positive (optical density >0.5) children with pulmonary symptoms were included. Of 506 serology-positive scrub typhus cases, 256 (50.5%) had pulmonary symptoms, of whom 50 (9.8%) were severe. These severe cases were compared with non-severe cases. Interstitial pneumonitis was the commonest chest radiographic finding. Logistic regression analysis identified 'fever clearance time' >48 h, facial puffiness, maculopapular rash and anaemia to be significantly associated with severe pulmonary involvement.
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Exantema , Fiebre/etiología , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Tifus por Ácaros/diagnóstico , Niño , Preescolar , Femenino , Humanos , Lactante , Pulmón/microbiología , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/microbiología , Masculino , Orientia tsutsugamushi/aislamiento & purificación , Valor Predictivo de las Pruebas , Radiografía , Tifus por Ácaros/complicaciones , Tifus por Ácaros/diagnóstico por imagenRESUMEN
Interstitial lung disease (ILD), particularly idiopathic pulmonary fibrosis (IPF), has a poor prognosis. Corticosteroids are widely used in the treatment of acute exacerbation of ILD (AE-ILD). This study aimed to clarify the causes of AE-ILD, determine the efficacy of corticosteroids for treating AE-ILD, and detect differences in the mortality rate among subgroups of ILD. This was an observational retrospective single-center study. Patients with ILD who presented to the emergency department with acute respiratory symptoms from January 1, 2016, to December 31, 2018, were included. Patients with AE-ILD were classified into two groups depending on the prednisolone dose: low dose (0 to 1.0 mg/kg) or high dose (> 1.0 mg/kg). Mortality rates between patients with and without IPF were compared. This study included 182 patients with AE-ILD, including IPF (n = 117) and non-IPF (n = 65). Multivariate Cox regression analysis showed that corticosteroid dose (HR: 0.221, CI: 0.102-0.408, P < 0.001), initial P/F ratio (HR:0.995, CI:0.992-0.999, P = 0.006), and mechanical ventilation within 3 days of hospitalization (HR:4.205, CI:2.059-8.589, P < 0.001) were independent risk factors for mortality in patients with AE-ILD. This study showed that outcomes improve with higher doses of corticosteroids (> 1 mg/kg prednisolone) in patients with AE-non-IPF-ILD. However, this was not the case in patients with AE-IPF.
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Corticoesteroides/uso terapéutico , Progresión de la Enfermedad , Servicio de Urgencia en Hospital , Hospitalización , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedad Aguda , Anciano , Femenino , Humanos , Estimación de Kaplan-Meier , Enfermedades Pulmonares Intersticiales/microbiología , Enfermedades Pulmonares Intersticiales/mortalidad , Masculino , Modelos de Riesgos Proporcionales , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
Studying respiratory illness-specific microbial signatures and their interaction with other micro-residents could provide a better understanding of lung microbial ecology. Each respiratory illness has a specific disease etiology, however, so far no study has revealed disease-specific microbial markers. The present study was designed to determine disease-specific microbial features and their interactions with other residents in chronic obstructive pulmonary diseases (stable and exacerbated), sarcoidosis, and interstitial lung diseases. Broncho-alveolar lavage samples (n = 43) were analyzed by SSU rRNA gene sequencing to study the alveolar microbiome in these diseases. A predominance of Proteobacteria followed by Firmicutes, Bacteroidetes, Actinobacteria, and Fusobacteria was observed in all the disease subsets. Shannon diversity was significantly higher in stable COPD when compared to exacerbated chronic obstructive pulmonary disease (ECOPD) (p = 0.0061), and ILD patient samples (p = 0.037). The lung microbiome of the patients with stable COPD was more diverse in comparison to ECOPD and ILD patients (p < 0.001). Lefse analysis identified 40 disease-differentiating microbial features (LDA score (log10) > 4). Species network analysis indicated a significant correlation (p < 0.05) of diseases specific microbial signature with other lung microbiome members. The current study strengthens the proposed hypothesis that each respiratory illness has unique microbial signatures. These microbial signatures could be used as diagnostic markers to differentiate among various respiratory illnesses.
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Enfermedades Pulmonares Intersticiales/microbiología , Enfermedad Pulmonar Obstructiva Crónica/microbiología , Sarcoidosis/microbiología , Anciano , Bacterias/genética , Lavado Broncoalveolar , Diagnóstico Diferencial , Femenino , Humanos , Pulmón/microbiología , Masculino , Microbiota/genética , Persona de Mediana Edad , ARN Ribosómico 16S/genéticaRESUMEN
BACKGROUND: Intravesical administration of Bacillus Calmette-Guérin (BCG) has proven useful for treatment and prevention of recurrence of superficial bladder cancer and in situ carcinoma. However, fatal side effects such as disseminated infections may occur. Early diagnosis and accurate therapy for interstitial pneumonitis (IP) are important because exacerbation of IP triggered by infections is the major cause of death. Although some fatality reports have suggested newly appeared IP after intravesical BCG treatment, to our knowledge, there are no reports which have demonstrated acute exacerbation of existing IP. Moreover, autopsy is lacking in previous reports. We report the case of a patient with fatal IP exacerbation after BCG instillation and the pathological findings of the autopsy. CASE PRESENTATION: A 77-year-old man with a medical history of IP was referred to our hospital because of fever and malaise. He had received an intravesical injection of BCG 1 day before the admission. His fever reduced after the use of antituberculosis drugs, so he was discharged home. He was referred to our hospital again because of a high fever 7 days after discharge. On hospitalisation, he showed high fever and systemic exanthema. Hepatosplenomegaly and myelosuppression were also observed. Biopsies revealed multiple epithelioid cell granulomas with Langhans giant cells of the liver and bone marrow. Biopsy DNA analyses of Mycobacterium bovis in the bone marrow, sputum, and blood were negative. His oxygen demand worsened drastically, and the ground-glass shadow expanded on the computed tomography scan. He was diagnosed with acute exacerbation of existing IP. We recommenced the antituberculosis drugs with steroid pulse therapy, but he died on day 35 because of respiratory failure. The autopsy revealed a diffuse appearance of multiple epithelioid cell granulomas with Langhans giant cells in multiple organs, although BCG was not evident. CONCLUSIONS: We report the first case of acute exacerbation of chronic IP by BCG infection. This is also the first case of autopsy of a patient with acute exacerbation of existing IP induced by intravesical BCG treatment. Whether the trigger of acute IP exacerbation is infection or hypersensitivity to BCG is still controversial, because pathological evidence confirming BCG infection is lacking. Physicians who administer BCG against bladder cancer should be vigilant for acute exacerbation of IP.
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Antituberculosos/uso terapéutico , Vacuna BCG/efectos adversos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/etiología , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/etiología , Esteroides/uso terapéutico , Brote de los Síntomas , Administración Intravesical , Anciano , Autopsia , Vacuna BCG/administración & dosificación , Vacuna BCG/uso terapéutico , Carcinoma in Situ/tratamiento farmacológico , Carcinoma in Situ/prevención & control , Resultado Fatal , Humanos , Enfermedades Pulmonares Intersticiales/microbiología , Masculino , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Mycobacterium bovis/genética , Resultados Negativos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/prevención & control , Quimioterapia por Pulso , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/prevención & controlAsunto(s)
Lavado Broncoalveolar/métodos , COVID-19/diagnóstico , Enfermedades Pulmonares Intersticiales/diagnóstico , SARS-CoV-2/aislamiento & purificación , Anciano , Anciano de 80 o más Años , COVID-19/epidemiología , COVID-19/virología , Prueba de COVID-19 , Coinfección/diagnóstico , Coinfección/microbiología , Coinfección/virología , Errores Diagnósticos , Femenino , Humanos , Inmunoglobulina G/análisis , Inmunoglobulina M , Italia/epidemiología , Enfermedades Pulmonares Intersticiales/microbiología , Enfermedades Pulmonares Intersticiales/virología , Masculino , Persona de Mediana Edad , Pandemias , Sensibilidad y Especificidad , Manejo de EspecímenesAsunto(s)
Hidroxicloroquina/uso terapéutico , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Anciano , Coxiella burnetii/patogenicidad , Coxiella burnetii/fisiología , Doxiciclina/administración & dosificación , Endocarditis Bacteriana/complicaciones , Endocarditis Bacteriana/diagnóstico , Endocarditis Bacteriana/tratamiento farmacológico , Femenino , Humanos , Hidroxicloroquina/administración & dosificación , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/microbiología , Cumplimiento de la Medicación , Paniculitis/tratamiento farmacológico , Paniculitis/etiología , Paniculitis/microbiología , Fiebre Q/complicaciones , Fiebre Q/diagnóstico , Fiebre Q/tratamiento farmacológico , Radiografía Torácica , Inducción de Remisión , Choque Séptico/complicaciones , Choque Séptico/diagnóstico , Choque Séptico/tratamiento farmacológicoRESUMEN
BACKGROUND: The presence of the human lung microbiota has been demonstrated in patients with different lung diseases, mainly in sputum samples. However, for study of the alveolar microbiota, a bronchoalveolar lavage (BAL) sample represents the lower respiratory tract (LRT) environment. It is currently unknown whether there is a specific alveolar microbiota profile in human lung diseases, such as pulmonary tuberculosis (TB) and interstitial pneumonia (IP). METHODS: BAL samples from six active TB patients, six IP patients and ten healthy volunteers were used for DNA extraction followed by amplification of the complete bacterial 16S ribosomal RNA gene (16S rDNA). The 16S rDNA was sequenced with a MiSeq Desktop Sequencer, and the data were analysed by QIIME software for taxonomic assignment. RESULTS: The alveolar microbiota in TB and IP patients and healthy volunteers was characterized by six dominant phyla, Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, Fusobacteria and Cyanobacteria. A significant reduction in the abundance of Firmicutes was observed in IP patients. In TB and IP patients, the diversity of the alveolar microbiota was diminished, characterized by a significant reduction in the abundance of the Streptococcus genus and associated with increased Mycobacterium abundance in TB patients and diminished Acinetobacter abundance in IP patients with respect to their abundances in healthy volunteers. However, an important difference was observed between TB and IP patients: the Fusobacterium abundance was significantly reduced in TB patients. Exclusive genera that were less abundant in patients than in healthy volunteers were characterized for each study group. CONCLUSIONS: This study shows that the alveolar microbiota profile in BAL samples from TB and IP patients, representing infectious and non-infectious lung diseases, respectively, is characterized by decreased diversity.
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Enfermedades Pulmonares Intersticiales/microbiología , Microbiota , Tuberculosis Pulmonar/microbiología , Actinobacteria/aislamiento & purificación , Actinobacteria/metabolismo , Adulto , Anciano , Bacteroidetes/aislamiento & purificación , Bacteroidetes/metabolismo , Lavado Broncoalveolar , Cianobacterias/aislamiento & purificación , Cianobacterias/metabolismo , Femenino , Firmicutes/aislamiento & purificación , Firmicutes/metabolismo , Fusobacterias/aislamiento & purificación , Fusobacterias/metabolismo , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Proteobacteria/aislamiento & purificación , Proteobacteria/metabolismo , ARN Bacteriano/genética , ARN Bacteriano/aislamiento & purificación , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/aislamiento & purificación , Sistema Respiratorio/microbiología , Esputo/microbiología , Adulto JovenRESUMEN
No disponible
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Humanos , Masculino , Femenino , Adulto , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/microbiología , Broncoscopía , Ceftriaxona/administración & dosificación , Micosis/sangre , Radiografía Torácica , Levofloxacino , Tomografía Computarizada por Rayos X , Itraconazol/uso terapéuticoRESUMEN
We report a case of primary pulmonary cryptococcosis in a 59-year-old female patient with a history of systemic lupus erythematosus, interstitial lung disease and glaucoma. She presented with a cough, severe fatigue, unintentional weight loss, shortness of breath (increase in home oxygen use from baseline) and pleuritic chest pain of 2 months duration. During these 2 months, her symptoms had worsened despite multiple hospital visits, empirical antibiotics and empirical increase of her steroid dosage. Cytopathology of the bronchoalveolar lavage fluid showed yeast cells with narrow-based budding and grew Cryptococcus neoformans on fungal culture. She was treated with oral fluconazole 400 mg/day for 6 months with an improvement in cough, decrease in shortness of breath (return to baseline oxygen use) and resolution of pleuritic chest pain.
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Líquido del Lavado Bronquioalveolar/microbiología , Criptococosis , Cryptococcus neoformans/aislamiento & purificación , Fluconazol/administración & dosificación , Enfermedades Pulmonares Intersticiales , Pulmón , Lupus Eritematoso Sistémico , Antifúngicos/administración & dosificación , Criptococosis/diagnóstico , Criptococosis/tratamiento farmacológico , Criptococosis/fisiopatología , Femenino , Glucocorticoides/uso terapéutico , Humanos , Huésped Inmunocomprometido , Pulmón/diagnóstico por imagen , Pulmón/microbiología , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/microbiología , Enfermedades Pulmonares Intersticiales/fisiopatología , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/terapia , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Treatment of chronic lung infection becomes a great challenge due to the drug resistant bacteria. In this scenario, evolving a new drug based on lipid metal conjugation loaded with potential antibiotic provides better drug delivery. In this study, ciprofloxacin loaded selenium-lipid nanoparticle (CxLSENPs) is produced in a novel route and its antimicrobial properties were tested against clinically important Gram-negative P. aeruginosa. The synthesized CxLSENPs was characterized by biophysical techniques (UV, Fluorescence spectroscopy, Raman spectroscopy, FTIR, FESEM, HRTEM and Zeta potential). Raman spectra coupled with FTIR spectra confirmed the possible interaction of lipid components in the NPs. HRTEM analysis confirmed the spherical shape of NPs. CxLSENPs recorded greater antibacterial effects on P. aeruginosa. A drastic reduction in the count of P. aeruginosa was observed after treatment with CxLSENPs. In order to further confirm the antibacterial efficiency, the live/dead cell assay was carried out. Live/dead analysis helps us to investigate the viability of bacterial cells. The number of dead bacterial cells was significantly higher in CxLSENPs treated groups when compare to the control. Furthermore, CxLSENPs increased the antioxidant enzyme activities (SOD, GPx, CAT and LPO) in mouse and protected the liver damage from bacterial infection. This study concludes that the developed CxLSENPs might be employed as strong antimicrobial and antioxidant agents for treating lung infection or interstitial lung diseases.
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Antibacterianos/química , Ciprofloxacina/química , Portadores de Fármacos/síntesis química , Lípidos/química , Nanopartículas/química , Selenio/química , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antioxidantes/metabolismo , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/prevención & control , Catalasa/metabolismo , Ciprofloxacina/farmacología , Ciprofloxacina/uso terapéutico , Portadores de Fármacos/química , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/microbiología , Enfermedades Pulmonares Intersticiales/patología , Masculino , Ratones , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/aislamiento & purificación , Superóxido Dismutasa/metabolismoRESUMEN
BACKGROUND: Sarcoidosis is a systemic disease of unknown etiology. The disease mechanisms are largely speculative and may include the role microbial patterns that initiate and drive an underlying immune process. The aim of this study was to characterize the microbiota of the lung of patients with sarcoidosis and compare its composition and diversity with the results from patients with other interstitial lung disease (ILD) and historic healthy controls. METHODS: Patients (sarcoidosis, n = 31; interstitial lung disease, n = 19) were recruited within the PULMOHOM study, a prospective cohort study to characterize inflammatory processes in pulmonary diseases. Bronchoscopy of the middle lobe or the lingula was performed and the recovered fluid was immediately sent for analysis of the pulmonary microbiota by 16sRNA gene sequencing. Subsequent bioinformatic analysis was performed to compare the groups. RESULTS: There were no significant differences between patients with sarcoidosis or other ILDs with regard to microbiome composition and diversity. In addition, the abundance of the genera Atopobium, Fusobacterium, Mycobacterium or Propionibacterium were not different between the two groups. There were no gross differences to historical healthy controls. CONCLUSION: The analysis of the pulmonary microbiota based on 16sRNA gene sequencing did not show a significant dysbiosis in patients with sarcoidosis as compared to other ILD patients. These data do not exclude a microbiological component in the pathogenesis of sarcoidosis.
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Líquido del Lavado Bronquioalveolar/microbiología , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/microbiología , Microbiota/fisiología , Sarcoidosis Pulmonar/diagnóstico , Sarcoidosis Pulmonar/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: RGM medium is an agar-based, selective culture medium designed for the isolation of nontuberculous mycobacteria (NTM) from the sputum of patients with cystic fibrosis (CF). We evaluated RGM medium for the detection of NTM in patients with CF (405 samples), bronchiectasis (323 samples) and other lung diseases necessitating lung transplantation (274 samples). METHODS: In total, 1002 respiratory samples from 676 patients were included in the study. Direct culture on RGM medium, with incubation at two temperatures (30 °C and 37 °C), was compared with conventional culture of decontaminated samples for acid-fast bacilli (AFB) using both a solid medium (Löwenstein-Jensen medium) and a liquid medium (the Mycobacterial Growth Indicator Tube; MGIT). RESULTS: For all three patient groups, significantly more isolates of NTM were recovered using RGM medium incubated at 30 °C than by any other method (sensitivity: 94.6% vs. 22.4% for conventional AFB culture; P < 0.0001). Significantly more isolates of Mycobacterium abscessus complex were isolated on RGM at 30 °C than by AFB culture (sensitivity: 96.1% vs. 58.8%; P < 0.0001). The recovery of Mycobacterium avium complex was also greater using RGM medium at 30 °C compared to AFB culture (sensitivity: 83% vs. 70.2%), although this difference was not statistically significant and a combination of methods was necessary for optimal recovery (P = 0.21). CONCLUSIONS: In the largest study of RGM medium to date, we reaffirm its utility for isolation of NTM from patients with CF. Furthermore; we show that it also provides an effective tool for culture of respiratory samples from patients with bronchiectasis and other lung diseases.
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Bronquiectasia/microbiología , Fibrosis Quística/microbiología , Enfermedades Pulmonares Intersticiales/microbiología , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Micobacterias no Tuberculosas/aislamiento & purificación , Enfermedad Pulmonar Obstructiva Crónica/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Medios de Cultivo , Técnicas de Cultivo , Femenino , Humanos , Enfermedades Pulmonares/microbiología , Trasplante de Pulmón , Masculino , Persona de Mediana Edad , Mycobacterium abscessus/aislamiento & purificación , Complejo Mycobacterium avium/aislamiento & purificación , Infección por Mycobacterium avium-intracellulare/diagnóstico , Sensibilidad y Especificidad , Esputo , Adulto JovenRESUMEN
Three Florida pumas ( Puma concolor coryi) that had spent time in captivity prior to being released in the wild were found exhibiting respiratory signs and reluctance to move. All 3 pumas died shortly after immobilization, despite supportive veterinary care. Significant autopsy findings included necrotizing interstitial pneumonia, with pulmonary edema and hyaline membranes, and suppurative myocarditis. Organisms morphologically consistent with Bartonella henselae were identified in intravascular histiocytes in the lung of one of the pumas on histopathology and confirmed via transmission electron microscopy. B. henselae was detected in fresh lung tissue and confirmed by PCR and sequence analysis (16S-23S spacer region, pap31, and rpoB genes) from one of the affected pumas. In all affected pumas, B. henselae was detected by PCR in formalin-fixed, paraffin-embedded lung tissue, and positively staining organisms were identified in sections of lung by immunohistochemistry for B. henselae. In situ hybridization detected B. henselae DNA in lung tissue from 2 of 3 affected pumas. Our case series suggests that B. henselae can be associated with a fatal disease syndrome in Florida pumas. The cause of susceptibility to fatal disease associated with B. henselae infection in these pumas remains unknown.