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1.
Lancet Respir Med ; 9(8): 885-896, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33961805

RESUMO

BACKGROUND: Infection is a key component of bronchiectasis pathophysiology. Characterisation of the microbiome offers a higher degree of sensitivity and resolution than does traditional culture methods. We aimed to evaluate the role of the microbiome in determining the risk of exacerbation and long-term outcomes, including all-cause mortality, in bronchiectasis. METHODS: We did a prospective observational cohort study of patients with bronchiectasis from eastern Scotland. Patients were enrolled from Sept 11, 2012, to Dec 21, 2015, and followed until Jan 8, 2019, for long-term outcomes. Patients were included if they were aged 18 years or older, and had a high-resolution CT-confirmed diagnosis of bronchiectasis and clinical symptoms consistent with the disease. Sputum samples were obtained when patients were clinically stable. Repeat sputum samples were taken at stable and exacerbation visits during follow-up. The V3-V4 region of the bacterial 16S rRNA gene was sequenced using the Illumina MiSeq platform. The dominant bacterial genus in each sample was assigned on the basis of a previously published method. Microbiome characteristics were analysed for their association with measures of clinical disease severity and long-term outcomes using PERMANOVA, random forest, and survival analyses. FINDINGS: Sequencing data were obtained from the sputum samples of 281 patients with bronchiectasis who were included in the stable baseline cohort. 49 (17%) of 281 patients provided more than one sample when clinically stable and were included in the longitudinal analysis. 64 (23%) patients provided both stable and exacerbation samples. In both stable bronchiectasis and during exacerbations, a sputum microbiome dominated by Proteobacteria and Firmicutes was observed. Individual patients' microbiome profiles were relatively stable over time, during exacerbations and at disease stability. Lower microbiome diversity, measured using the Shannon-Wiener diversity index, was associated with more severe bronchiectasis defined by the bronchiectasis severity index, lower FEV1, and more severe symptoms. Random forest analysis of baseline samples identified Pseudomonas, Enterobacteriaceae, and Stenotrophomonas as being associated with severe bronchiectasis (bronchiectasis severity index ≥9) and greater lung inflammation and Pseudomonas and Enterobacteriaceae with more frequent exacerbations. Patients in whom Pseudomonas was dominant (n=35) were at increased risk of all-cause mortality (hazard ratio 3·12, 95% CI 1·33-7·36; p=0·0091) and had more frequent exacerbations (incident rate ratio 1·69, 95% CI 1·07-2·67; p=0·024) during follow-up compared with patients with other dominant genera (n=246). INTERPRETATION: A reduction in microbiome diversity, particularly one associated with dominance of Pseudomonas, is associated with greater disease severity, higher frequency and severity of exacerbations, and higher risk of mortality. The microbiome might therefore identify subgroups of patients at increased risk of poor outcomes who could benefit from precision treatment strategies. Further research is required to identify the mechanisms of reduced microbiome diversity and to establish whether the microbiome can be therapeutically targeted. FUNDING: British Lung Foundation and European Respiratory Society EMBARC2 consortium.


Assuntos
Bronquiectasia/microbiologia , Microbiota , Escarro/microbiologia , Idoso , Bronquiectasia/mortalidade , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Testes de Função Respiratória , Índice de Gravidade de Doença
2.
Respir Res ; 22(1): 132, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910573

RESUMO

BACKGROUND: Pseudomonas aeruginosa is one of the commonest bacteria colonizing the airway in patients with non-cystic fibrosis bronchiectasis. Pseudomonas aeruginosa colonization is associated with poor outcomes in patients with bronchiectasis, including rapid decline in lung function, exacerbation frequency and hospitalization. METHODS: A cross-sectional study in Queen Mary Hospital, Hong Kong that included 350 Chinese patients with non-cystic fibrosis bronchiectasis to investigate the risk factors for Pseudomonas aeruginosa colonization and clinical implications on disease outcomes. DISCUSSIONS: Pseudomonas aeruginosa colonization was more commonly found in patients with longer duration of bronchiectasis and those on proton pump inhibitors (PPIs) with adjusted ORs of 1.066 (95% CI = 1.036-1.096, p < 0.001) and 2.815 (95% CI = 1.307-6.064, p = 0.008) respectively. Patients with Pseudomonas aeruginosa colonization have more extensive lung involvement and higher risks of exacerbation requiring hospitalization with adjusted ORs of 2.445 (95% CI = 1.283-4.657, p = 0.007) and 2.745 (95% CI = 1.012-7.449, p = 0.047) respectively. Pseudomonas aeruginosa colonization is more common among patients with longer duration of bronchiectasis and those on PPI. Pseudomonas aeruginosa colonization is associated with more extensive lung involvement and higher risks of exacerbation requiring hospitalization.


Assuntos
Bronquiectasia/microbiologia , Pulmão/microbiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/crescimento & desenvolvimento , Idoso , Idoso de 80 Anos ou mais , Bronquiectasia/diagnóstico , Bronquiectasia/terapia , Estudos Transversais , Progressão da Doença , Feminino , Hong Kong , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/uso terapêutico , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/terapia , Medição de Risco , Fatores de Risco , Fatores de Tempo
3.
Nat Med ; 27(4): 688-699, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33820995

RESUMO

Bronchiectasis, a progressive chronic airway disease, is characterized by microbial colonization and infection. We present an approach to the multi-biome that integrates bacterial, viral and fungal communities in bronchiectasis through weighted similarity network fusion ( https://integrative-microbiomics.ntu.edu.sg ). Patients at greatest risk of exacerbation have less complex microbial co-occurrence networks, reduced diversity and a higher degree of antagonistic interactions in their airway microbiome. Furthermore, longitudinal interactome dynamics reveals microbial antagonism during exacerbation, which resolves following treatment in an otherwise stable multi-biome. Assessment of the Pseudomonas interactome shows that interaction networks, rather than abundance alone, are associated with exacerbation risk, and that incorporation of microbial interaction data improves clinical prediction models. Shotgun metagenomic sequencing of an independent cohort validated the multi-biome interactions detected in targeted analysis and confirmed the association with exacerbation. Integrative microbiomics captures microbial interactions to determine exacerbation risk, which cannot be appreciated by the study of a single microbial group. Antibiotic strategies probably target the interaction networks rather than individual microbes, providing a fresh approach to the understanding of respiratory infection.


Assuntos
Bronquiectasia/microbiologia , Microbiota , Bronquiectasia/virologia , Progressão da Doença , Humanos , Metagenômica , Interações Microbianas/genética , Microbiota/genética , Filogenia
4.
Lancet Respir Med ; 9(8): 873-884, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33609487

RESUMO

BACKGROUND: Bronchiectasis is predominantly a neutrophilic inflammatory disease. There are no established therapies that directly target neutrophilic inflammation because little is understood of the underlying mechanisms leading to severe disease. Neutrophil extracellular trap (NET) formation is a method of host defence that has been implicated in multiple inflammatory diseases. We aimed to investigate the role of NETs in disease severity and treatment response in bronchiectasis. METHODS: In this observational study, we did a series of UK and international studies to investigate the role of NETs in disease severity and treatment response in bronchiectasis. First, we used liquid chromatography-tandem mass spectrometry to identify proteomic biomarkers associated with disease severity, defined using the bronchiectasis severity index, in patients with bronchiectasis (n=40) in Dundee, UK. Second, we validated these biomarkers in two cohorts of patients with bronchiectasis, the first comprising 175 patients from the TAYBRIDGE study in the UK and the second comprising 275 patients from the BRIDGE cohort study from centres in Italy, Spain, and UK, using an immunoassay to measure NETs. Third, we investigated whether pathogenic bacteria had a role in NET concentrations in patients with severe bronchiectasis. In a separate study, we enrolled patients with acute exacerbations of bronchiectasis (n=20) in Dundee, treated with intravenous antibiotics for 14 days and proteomics were used to identify proteins associated with treatment response. Findings from this cohort were validated in an independent cohort of patients who were admitted to the same hospital (n=20). Fourth, to assess the potential use of macrolides to reduce NETs in patients with bronchiectasis, we examined two studies of long-term macrolide treatment, one in patients with bronchiectasis (n=52 from the UK) in which patients were given 250 mg of azithromycin three times a week for a year, and a post-hoc analysis of the Australian AMAZES trial in patients with asthma (n=47) who were given 500 mg of azithromycin 3 times per week for a year. FINDINGS: Sputum proteomics identified that NET-associated proteins were the most abundant and were the proteins most strongly associated with disease severity. This finding was validated in two observational cohorts, in which sputum NETs were associated with bronchiectasis severity index, quality of life, future risk of hospital admission, and mortality. In a subgroup of 20 patients with acute exacerbations, clinical response to intravenous antibiotic treatment was associated with successfully reducing NETs in sputum. Patients with Pseudomonas aeruginosa infection had a lessened proteomic and clinical response to intravenous antibiotic treatment compared with those without Pseudomonas infections, but responded to macrolide therapy. Treatment with low dose azithromycin was associated with a significant reduction in NETs in sputum over 12 months in both bronchiectasis and asthma. INTERPRETATION: We identified NETs as a key marker of disease severity and treatment response in bronchiectasis. These data support the concept of targeting neutrophilic inflammation with existing and novel therapies. FUNDING: Scottish Government, British Lung Foundation, and European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC).


Assuntos
Antibacterianos/administração & dosagem , Azitromicina/administração & dosagem , Bronquiectasia/tratamento farmacológico , Armadilhas Extracelulares/metabolismo , Macrolídeos/administração & dosagem , Infecções por Pseudomonas/tratamento farmacológico , Biomarcadores/análise , Bronquiectasia/microbiologia , Estudos de Coortes , Humanos , Proteômica , Pseudomonas aeruginosa/efeitos dos fármacos , Testes de Função Respiratória , Índice de Gravidade de Doença , Escarro/microbiologia
5.
Chest ; 159(4): 1372-1381, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33080299

RESUMO

Management of Mycobacterium avium complex (MAC) lung disease is complicated, frequently unsuccessful, and frustrating to patients and clinicians. The initial treatment effort may not be directed solely at MAC infection, rather it is often initiating airway clearance measures for bronchiectasis. The next important steps are deciding who to treat and when to initiate therapy. Definitive or unambiguous guidance for these decisions is often elusive. The evidence supporting the current macrolide-based regimen for treating MAC lung disease is compelling. This regimen has been recommended in consensus nontuberculous mycobacterial treatment guidelines from 1997, 2007, and 2020, although clinician compliance with these recommendations is inconsistent. Understanding the idiosyncrasies of MAC antibiotic resistance is crucial for optimal antibiotic management. As a corollary, the importance of avoiding development of macrolide resistance due to inadequate therapy cannot be overstated. An inhaled liposome amikacin preparation is now approved for treating refractory MAC lung disease and holds promise for an even broader role in MAC therapy. Surgery is also an important therapeutic adjunct for selected patients. Microbiologic recurrences due either to new infection or treatment relapse/failure are common and require the same level of rigorous assessment and clinical judgment for determining their significance as initial MAC isolates. In summary, treatment of patients with MAC lung disease is rarely straight forward and requires familiarity with multiple factors directly and indirectly related to MAC lung disease. The many nuances of MAC lung disease therapy defy simple treatment algorithms; however, with patience, attention to detail, and perseverance, the outcome for most patients is favorable.


Assuntos
Antibacterianos/uso terapêutico , Pneumopatias/tratamento farmacológico , Complexo Mycobacterium avium/efeitos dos fármacos , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Bronquiectasia/tratamento farmacológico , Bronquiectasia/microbiologia , Farmacorresistência Bacteriana , Humanos , Testes de Sensibilidade Microbiana
6.
Clin Microbiol Infect ; 27(3): 428-434, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32311472

RESUMO

OBJECTIVES: The objective of this study was to analyse lung function decline over time in bronchiectasis, along with the factors associated with it. METHODS: Spirometry was measured every year in this observational, prospective study in 849 patients from the Spanish Bronchiectasis Registry (RIBRON). The main outcome was the decline in the rate of forced expiratory volume during the first second (FEV1). To be included in this study, patients needed a baseline assessment and at least one subsequent assessment. FEV1 decline was analysed using a mixed-effects linear regression model adjusted for clinically significant variables. RESULTS: We recruited 849 bronchiectasis patients with at least two annual lung function measurements (follow-up range 1-4 years). A total of 2262 lung function tests were performed (mean 2.66 per patient, range 2-5). Mean baseline FEV1 was 1.78 L (standard deviation (SD) 0.76; 71.3% predicted). Mean age was 69.1 (SD 15.4) years; 543 (64% women. The adjusted rates of FEV1 decline were -0.98% predicted/year (95% confidence interval (CI) -2.41 to -0.69) and -31.6 (95% CI -44.4 to -18.8) mL. The annual FEV1 decline was faster in those patients with chronic bronchial infection by Pseudomonas aeruginosa (-1.37% (52.1 mL) vs -0.37% (-24.6 mL); p < 0.001), greater age, increased number of severe exacerbations in the previous year and higher baseline FEV1 value. DISCUSSION: In patients with bronchiectasis, the annual rate of FEV1 decline was -31.6 mL/year and it was faster in older patients and those with chronic bronchial infection by P. aeruginosa, increased number of previous severe exacerbations and higher baseline FEV1 value.


Assuntos
Bronquiectasia/complicações , Bronquiectasia/microbiologia , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória
7.
Respirology ; 26(1): 112-119, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32602203

RESUMO

BACKGROUND AND OBJECTIVE: The lack of useful biomarkers reflecting the disease state limits the management of Mycobacterium avium complex lung disease (MAC-LD). We clarified the associations between serum KL-6 level, disease progression and treatment response. METHODS: Resected lung tissues from MAC-LD patients were immunostained for KL-6. We compared serum KL-6 levels between MAC-LD and healthy control or bronchiectasis patients without nontuberculous mycobacterial lung disease (NTM-LD). Serum KL-6 level was assessed in a prospective observational study at Keio University Hospital between May 2012 and May 2016. We investigated associations between serum KL-6 level and disease progression and treatment response in patients untreated for MAC-LD on registration (n = 187). RESULTS: The KL-6+ alveolar type 2 cell population in the lung and serum KL-6 level were significantly higher in MAC-LD patients than in controls. Serum KL-6 level in bronchiectasis patients without NTM-LD showed no significant increase. Of the 187 patients who did not receive treatment on registration, 53 experienced disease progression requiring treatment. Multivariable Cox analysis revealed that the serum KL-6 level (aHR: 1.18, P = 0.005), positive acid-fast bacilli smear (aHR: 2.64, P = 0.001) and cavitary lesions (aHR: 3.01, P < 0.001) were significantly associated with disease progression. The change in serum KL-6 (ΔKL-6) was significantly higher in the disease progression group; it decreased post-treatment, reflecting the negative sputum culture conversion. CONCLUSION: Serum KL-6 level is associated with disease progression and treatment response. Longitudinal assessment combined with AFB smear status and presence of cavitary lesions may aid MAC-LD management.


Assuntos
Progressão da Doença , Mucina-1/sangue , Complexo Mycobacterium avium/fisiologia , Infecção por Mycobacterium avium-intracellulare/sangue , Infecção por Mycobacterium avium-intracellulare/microbiologia , Idoso , Biomarcadores , Bronquiectasia/sangue , Bronquiectasia/complicações , Bronquiectasia/microbiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Pulmão/metabolismo , Pulmão/microbiologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infecção por Mycobacterium avium-intracellulare/mortalidade , Infecção por Mycobacterium avium-intracellulare/patologia , Modelos de Riscos Proporcionais , Estudos Prospectivos
9.
Respiration ; 99(11): 961-969, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33264771

RESUMO

BACKGROUND: There is no study on the predictive factors of recurrent haemoptysis after bronchial artery embolization (BAE) with the long-term outcomes in patients with bronchiectasis (BE). OBJECTIVES: To evaluate the long-term outcomes of BAE in BE patients without accompanying refractory active infection of mycobacteriosis and aspergillosis with analysis for the predictive factors of recurrent haemoptysis. METHODS: Data of 106 patients with BE who underwent BAE using coils between January 2011 and December 2018 were retrospectively reviewed. The cumulative haemoptysis control rate was estimated using Kaplan-Meier methods with log-rank tests to analyze differences in recurrence-free rate between groups based on technical success and failure, bacterial colonization status, number of BE lesions, and vessels embolized to bronchial arteries (BAs) or BAs + non-bronchial systemic arteries (NBSAs). RESULTS: Bacterial colonization was detected in approximately 60% of patients. Computed tomography showed bronchiectatic lesions with 2.9 ± 1.4 lobes. In the first series of BAE, embolization was performed in the BAs alone and BAs + NBSAs in 65.1 and 34.9% of patients, respectively, with 2.4 ± 1.4 embolized vessels in total. The median follow-up period was 1,000 (7-2,790) days. The cumulative haemoptysis control rates were 91.3, 84.2, 81.5, and 78.9% at 1, 2, 3, and 5 years, respectively. The haemoptysis control rates were higher in the technical success group than in the technical failure group (p = 0.029). CONCLUSIONS: High haemoptysis control rates for long-term periods were obtained by embolization for all visualized abnormal arteries, regardless of the colonization status, number of bronchiectatic lobes, and target vessels, irrespective of NBSAs.


Assuntos
Bronquiectasia/terapia , Embolização Terapêutica , Hemoptise/terapia , Brônquios/diagnóstico por imagem , Artérias Brônquicas/diagnóstico por imagem , Artérias Brônquicas/microbiologia , Bronquiectasia/complicações , Bronquiectasia/microbiologia , Angiografia por Tomografia Computadorizada , Hemoptise/etiologia , Humanos , Estimativa de Kaplan-Meier , Recidiva , Estudos Retrospectivos , Prevenção Secundária , Resultado do Tratamento
10.
Medicine (Baltimore) ; 99(39): e22475, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991486

RESUMO

RATIONALE: Although bronchiectasis is conventionally considered a chronic pulmonary disease of adulthood, knowledge of pediatric bronchiectasis not related to cystic fibrosis started to emerge. Limited information in this field is available and the management is based on expert opinion. PATIENT CONCERNS: An 8-year-old girl admitted for 7 days history of wet cough, purulent fetid sputum, shortness of breath and low-grade fever. The wet cough has presented for the past 4 years, during which she had frequent hospitalization for recurrent lower respiratory tract infections. DIAGNOSIS: Chest high-resolution computerized tomography revealed diffuse bronchial dilations accompanied by inflammation in the bilateral lung fields. Microbiologic investigation for bronchoalveolar lavage fluid was positive for Pseudomonas aeruginosa. INTERVENTIONS: With a working diagnosis of bronchiectasis with secondary pulmonary infection, sensitive cefoperazone-sulbactam was administrated for 14 days with gradual improvement of clinical symptoms. Bronchoscopy washing substantially soothed the symptoms, reducing the cough and sputum volumes. OUTCOMES: The child was discharged after 14 days, and treated on long-term prophylactic antibiotic use (amoxicillin-clavulanic acid, 20 mg/kg/d, ≥ 4 weeks). LESSONS: Although bronchiectasisis are condition in childhood, the diagnosis is suspected in children with persistent wet or productive cough, and should be confirmed by a chest high-resolution computerized tomography scan. Antibiotics and airway clearance techniques represent the milestones of bronchiectasis management although there are only a few guidelines in children.


Assuntos
Bronquiectasia/complicações , Infecções por Pseudomonas/complicações , Pseudomonas aeruginosa/isolamento & purificação , Antibacterianos/administração & dosagem , Bronquiectasia/microbiologia , Criança , Feminino , Humanos , Infecções por Pseudomonas/tratamento farmacológico
11.
Rev. patol. respir ; 23(3): 108-110, jul.-sept. 2020. ilus
Artigo em Espanhol | IBECS | ID: ibc-198473

RESUMO

Mycobacterium lentiflavum infrecuentemente provoca patogenicidad en el ser humano, aunque se ha descrito como causante de linfadenitis cervical y afectación pulmonar. Generalmente presenta un curso clínico poco agresivo y se asocia un patrón radiológico nódulo-bronquiectásico. En nuestro caso relatamos un paciente con clínica respiratoria inespecífica y presencia de bronquiectasias y lesiones de morfología pseudonodular en la tomografía computarizada (TC) torácica. En la TC torácica de control y tomografía por emisión de positrones (PET) se evidenció aumento de tamaño y del metabolismo de dichas lesiones. Se realiza biopsia para descartar malignidad creciendo en cultivo de la muestra Mycobacterium lentiflavum


Mycobacterium lentiflavum infrequently causes pathogenicity in humans, although it has been identified as causing cervical lymphadenitis and lung involvement. It usually has a poorly aggressive clinical course and a nodule-bronchiectatic radiological pattern is associated. In our case, we report a patient with a nonspecific respiratory clinic and presence of bronchiectasis and pseudonodular morphology lesions in thoracic computed tomography. In the thoracic CT scan of positron emission tomography (PET) there was evidence of an increase in the size and metabolism of these lesions. Biopsy is performed to rule out malignancy, with Mycobacterium lentiflavum growing in sample culture


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium/isolamento & purificação , Infecções por Mycobacterium/microbiologia , Pneumonia Bacteriana/microbiologia , Bronquiectasia/microbiologia , Infecções por Mycobacterium/diagnóstico por imagem , Pneumonia Bacteriana/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Bronquiectasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons
12.
Expert Opin Pharmacother ; 21(16): 1975-1990, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32808825

RESUMO

INTRODUCTION: Effective management of both acute and chronic bronchial infections is mandatory due to their high frequency rate, the relevant morbidity and mortality and the significant burden to health care systems, especially with the aging of population. Bacteria are the main causative pathogens, followed by viruses, and less commonly by fungi. The clinical evaluation of new therapeutic associations is mandatory to cope with the increases in resistance, in association with better infection control and antimicrobial policies. AREAS COVERED: The authors searched Medline for any article published in English language up until March 1, 2020 that concerns the treatment of acute exacerbations and chronic infections in chronic obstructive respiratory disease and bronchiectasis. EXPERT OPINION: As acute exacerbations are a main common and detrimental event in patients with COPD and bronchiectasis, effective antimicrobial therapies and regimens should be optimized. The development of new molecules or combination regimens is vital to patients with severe and/or difficult-to-treat infections. Moreover, chronic infection control is mandatory in these patients to their improve quality of life, respiratory function and prognosis as well as for reducing health care costs.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Bronquiectasia/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Administração Oral , Adulto , Antibacterianos/administração & dosagem , Infecções Bacterianas/microbiologia , Bronquiectasia/microbiologia , Progressão da Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Humanos , Doença Pulmonar Obstrutiva Crônica/microbiologia , Qualidade de Vida
13.
Chest ; 158(4): 1376-1384, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32622820

RESUMO

BACKGROUND: In patients with bronchiectasis, airway clearance techniques (ACTs) are important management strategies. RESEARCH QUESTION: What are the differences in patients with bronchiectasis and a productive cough who used ACTs and those who did not? What was the assessment of bronchiectasis exacerbation frequency and change in pulmonary function at 1-year follow up? STUDY DESIGN AND METHODS: Adult patients with bronchiectasis and a productive cough in the United States Bronchiectasis and NTM Research Registry were included in the analyses. ACTs included the use of instrumental devices and manual techniques. Stratified analyses of demographic and clinical characteristics were performed by use of ACTs at baseline and follow up. The association between ACT use and clinical outcomes was assessed with the use of unadjusted and adjusted multinomial logistic regression models. RESULTS: Of the overall study population (n = 905), 59% used ACTs at baseline. A greater proportion of patients who used ACTs at baseline and follow up continuously had Pseudomonas aeruginosa (47% vs 36%; P = .021) and experienced an exacerbation (81% vs 59%; P < .0001) or hospitalization for pulmonary illness (32% vs 22%; P = .001) in the prior two years, compared with those patients who did not use ACTs. Fifty-eight percent of patients who used ACTs at baseline did not use ACTs at 1-year follow up. There was no significant change in pulmonary function for those who used ACTs at follow up, compared with baseline. Patients who used ACTs at baseline and follow up had greater odds for experiencing exacerbations at follow up compared with those patients who did not use ACTs. INTERPRETATION: In patients with bronchiectasis and a productive cough, ACTs are used more often if the patients have experienced a prior exacerbation, hospitalization for pulmonary illness, or had P aeruginosa. There is a significant reduction in the use of ACTs at 1-year follow up. The odds of the development of a bronchiectasis exacerbation are higher in those patients who use ACTs continuously, which suggests more frequent use in an ill bronchiectasis population.


Assuntos
Bronquiectasia/terapia , Terapia Respiratória , Idoso , Pesquisa Biomédica , Bronquiectasia/microbiologia , Estudos de Coortes , Tosse , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Micobactérias não Tuberculosas , Sistema de Registros , Estados Unidos
14.
Ther Adv Respir Dis ; 14: 1753466620936866, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32615859

RESUMO

BACKGROUND: The optimum antibiotic therapy for non-cystic fibrosis bronchiectasis (NCFB) has yet to be determined. A meta-analysis was conducted to evaluate the efficacy and safety of inhaled antibiotics in adults with stable NCFB. METHODS: PubMed, EMBASE, MEDLINE and the Cochrane Central Register of Controlled Trials were searched through November 2019. RESULTS: A total of 16 randomized controlled trials (RCTs), recruiting 2748 NCFB patients, were finally included. Inhaled antibiotics treatment significantly reduced the sputum bacterial load [standard mean difference (SMD) = -0.74, 95% CI: -1.16-0.32, p < 0.001, I2 = 68.1%], prolonged median time [hazard risk (HR) = 0.73, 95% confidence interval (CI): 0.57-0.93, p < 0.001, I2 = 53.6%] and reduced frequency [incidence rate ratio (IRR) = 0.74, 95% CI 0.63-0.87, p < 0.001, I2 = 20.5%] of exacerbations, with good tolerance. However, it failed to improve Pseudomonas aeruginosa eradication, [forced expiratory volume in 1 s (FEV1)] % predicted, quality of life questionnaire (QoL-B) and St. George's respiratory questionnaire (SGRQ) scores, and may induce higher risk of P. aeruginosa resistance. Subgroup analysis showed Ciprofloxacin was more effective than other antibiotics in reducing bacterial load (SMD = -1.35, 95% CI: -1.85-0.85, I2 = 63.4%, p = 0.042). CONCLUSION: Inhaled antibiotics therapy holds great promise for stable NCFB as it is effective in reducing sputum bacterial load and the risk of acute attack, delaying disease progression, and is well tolerated. Although this study brings some constructive ideas in the field of clinical medication, further clinical trials should be carried out, particularly in solving drug-resistance and improving health-related quality of life (HRQoL), which we believe will finally provide benefits for patients suffering from bronchiectasis. The reviews of this paper are available via the supplemental material section.


Assuntos
Antibacterianos/administração & dosagem , Bronquiectasia/tratamento farmacológico , Pulmão/efeitos dos fármacos , Administração por Inalação , Antibacterianos/efeitos adversos , Carga Bacteriana , Bronquiectasia/diagnóstico , Bronquiectasia/microbiologia , Bronquiectasia/fisiopatologia , Feminino , Humanos , Pulmão/microbiologia , Pulmão/fisiopatologia , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Escarro/microbiologia , Resultado do Tratamento
15.
Rev Mal Respir ; 37(7): 561-571, 2020 Sep.
Artigo em Francês | MEDLINE | ID: mdl-32684338

RESUMO

INTRODUCTION: Common major pathogens like Pseudomonas aeruginosa are identified in the airways of patients with cystic fibrosis (CF) and non-CF bronchiectasis. However, other opportunistic bacterial pathogens like Achromobacter xylosoxidans complex, Stenotrophomonas maltophilia and non-tuberculous mycobacteria are currently emerging in CF and are also reported in non-CF bronchiectasis. BACKGROUND: The emergence of opportunistic bacterial pathogens has been recognized in CF through annual national reports of sputum microbiology data. Despite common factors driving the emergence of bacteria identified in CF and non-CF bronchiectasis patients, bronchiectasis registries have been created more recently and no longitudinal analysis of recorded microbiological data is currently available in the literature, thereby preventing the recognition of emerging bacteria in patients with non-CF bronchiectasis. OUTLOOK: A longitudinal follow-up of microbiological data is still needed in non-CF bronchiectasis to identify emerging opportunistic bacterial pathogens. Homogeneity in practice of sputum microbiological examination is also required to allow comparative analysis of data in CF and non-CF bronchiectasis. CONCLUSION: Bacterial pathogens recognized as emerging in CF have to be more carefully monitored in non-CF bronchiectasis in view of their association with deterioration of the lung disease.


Assuntos
Bronquiectasia/microbiologia , Fibrose Cística/microbiologia , Microbiologia/tendências , Fibrose Pulmonar/microbiologia , Infecções Respiratórias/microbiologia , Bronquiectasia/complicações , Bronquiectasia/epidemiologia , Bronquiectasia/terapia , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/microbiologia , Doenças Transmissíveis Emergentes/terapia , Fibrose Cística/complicações , Fibrose Cística/epidemiologia , Fibrose Cística/terapia , Humanos , Técnicas Microbiológicas/estatística & dados numéricos , Técnicas Microbiológicas/tendências , Monitorização Fisiológica/métodos , Monitorização Fisiológica/normas , Monitorização Fisiológica/tendências , Infecções Oportunistas/epidemiologia , Infecções Oportunistas/microbiologia , Infecções Oportunistas/terapia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/epidemiologia , Fibrose Pulmonar/terapia , Infecções Respiratórias/complicações , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/terapia , Escarro/microbiologia
16.
BMC Pulm Med ; 20(1): 172, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546272

RESUMO

BACKGROUND: The prevalence of non-cystic fibrosis (CF) bronchiectasis is increasing in both developed and developing countries in recent years. Although the main features remain similar, etiologies seem to change. Our aim was to evaluate the clinical and laboratory characteristics of our recent non-CF bronchiectasis patients and to compare these with our historical cohort in 2001. METHODS: One hundred four children with non-CF bronchiectasis followed between 2002 and 2019 were enrolled. Age of diagnosis, underlying etiology and microorganisms in sputum culture were recorded. Clinical outcomes were evaluated in terms of lung function tests and annual pulmonary exacerbation rates at presentation and within the last 12 months. RESULTS: Mean FEV1 and FVC %predicted at presentation improved compared to historical cohort (76.6 ± 17.1 vs. 63.3 ± 22.1 and 76.6 ± 15.1 vs. 67.3 ± 23.1, respectively; p <  0.001). There was a significant decrease in pulmonary exacerbation rate from 6.05 ± 2.88 at presentation to 3.23 ± 2.08 during follow-up (p <  0.0001). In 80.8% of patients, an underlying etiology was identified. There was an increase in primary ciliary dyskinesia (PCD) (32.7% vs. 6.3%; p = 0.001), decrease in idiopathic cases (19.2% vs. 37.8%; p = 0.03) with no change in postinfectious and immunodeficiencies as underlying etiology. Sputum cultures were positive in 77.9% of patients which was 46.9% in the historical cohort (p = 0.001). CONCLUSION: Baseline pulmonary function tests were better and distribution of underlying etiology had changed with a remarkable increase in diagnosis of PCD in the recent cohort.


Assuntos
Bronquiectasia/etiologia , Bronquiectasia/microbiologia , Bronquiectasia/fisiopatologia , Transtornos da Motilidade Ciliar/complicações , Escarro/microbiologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Infecções/complicações , Masculino , Doenças da Imunodeficiência Primária/complicações , Testes de Função Respiratória , Índice de Gravidade de Doença , Espirometria
17.
Colloids Surf B Biointerfaces ; 193: 111095, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32416520

RESUMO

Antibiotic-polyelectrolyte nanoparticle complex (or nanoplex in short) has been recently demonstrated as a superior antibiotic delivery system to the native antibiotic in bronchiectasis therapy owed to its ability to overcome the lung's mucus barrier and generate high localized antibiotic exposure in the infected sites. The present work aimed to further improve the mucus permeability, hence the antibacterial efficacy of the nanoplex, by incorporating mucolytic enzyme papain (PAP) at the nanoplex formation step to produce PAP-decorated antibiotic-polyelectrolyte nanoplex exhibiting built-in mucolytic capability. Ciprofloxacin (CIP) and dextran sulfate (DXT) were used as the models for antibiotics and polyelectrolyte, respectively. The results showed that the PAP inclusion had minimal effects on the physical characteristics, preparation efficiency, and dissolution of the CIP-DXT nanoplex. The optimal CIP-(DXT-PAP) nanoplex exhibited size and zeta potential of approximately 200 nm and -50 mV with CIP and PAP payloads of 60% and 32% (w/w), respectively. The nanoplex was prepared at high efficiency with larger than 80% CIP and PAP utilization rates. The CIP-(DXT-PAP) nanoplex exhibited tenfold improvement in the mucus permeability compared to its CIP-DXT nanoplex counterpart, resulting in the former's superior bactericidal activity against clinical Pseudomonas aeruginosa biofilm in the presence of mucus barrier. A trade-off, nevertheless, existed between antibacterial efficacy and cytotoxicity towards human lung epithelium cells upon the incorporation of PAP above a certain concentration threshold. Therefore, the optimal dosing of the CIP-(DXT-PAP) nanoplex must be carefully determined.


Assuntos
Antibacterianos/farmacologia , Bronquiectasia/tratamento farmacológico , Ciprofloxacina/farmacologia , Sulfato de Dextrana/farmacologia , Nanopartículas/química , Papaína/química , Polieletrólitos/farmacologia , Antibacterianos/química , Antibacterianos/metabolismo , Biofilmes/efeitos dos fármacos , Bronquiectasia/microbiologia , Ciprofloxacina/química , Ciprofloxacina/metabolismo , Sulfato de Dextrana/química , Sulfato de Dextrana/metabolismo , Sistemas de Liberação de Medicamentos , Humanos , Testes de Sensibilidade Microbiana , Nanopartículas/metabolismo , Papaína/metabolismo , Tamanho da Partícula , Polieletrólitos/química , Polieletrólitos/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Propriedades de Superfície
18.
Int J Mol Sci ; 21(9)2020 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-32357408

RESUMO

BACKGROUND: Prior studies illustrate the presence and clinical importance of detecting Aspergillus species in the airways of patients with chronic respiratory disease. Despite this, a low fungal biomass and the presence of PCR inhibitors limits the usefulness of quantitative PCR (qPCR) for accurate absolute quantification of Aspergillus in specimens from the human airway. Droplet digital PCR (ddPCR) however, presents an alternative methodology allowing higher sensitivity and accuracy of such quantification but remains to be evaluated in head-to-head fashion using specimens from the human airway. Here, we implement a standard duplex TaqMan PCR protocol, and assess if ddPCR is superior in quantifying airway Aspergillus when compared to standard qPCR. METHODS: The molecular approaches of qPCR and ddPCR were applied to DNA fungal extracts in n = 20 sputum specimens obtained from non-diseased (n = 4), chronic obstructive pulmonary disease (COPD; n = 8) and non-cystic fibrosis bronchiectasis (n = 8) patients where Aspergillus status was known. DNA was extracted and qPCR and ddPCR performed on all specimens with appropriate controls and head-to-head comparisons performed. RESULTS: Standard qPCR and ddPCR were both able to detect, even at low abundance, Aspergillus species (Aspergillus fumigatus - A. fumigatus and Aspergillus terreus - A. terreus) from specimens known to contain the respective fungi. Importantly, however, ddPCR was superior for the detection of A. terreus particularly when present at very low abundance and demonstrates greater resistance to PCR inhibition compared to qPCR. CONCLUSION: ddPCR has greater sensitivity for A. terreus detection from respiratory specimens, and is more resistant to PCR inhibition, important attributes considering the importance of A. terreus species in chronic respiratory disease states such as bronchiectasis.


Assuntos
Aspergillus/isolamento & purificação , Bronquiectasia/microbiologia , Reação em Cadeia da Polimerase/métodos , Aspergilose Pulmonar/diagnóstico , Doença Pulmonar Obstrutiva Crônica/microbiologia , Idoso , Aspergillus/genética , Carga Bacteriana , Estudos de Casos e Controles , DNA Fúngico/genética , Diagnóstico Precoce , Feminino , Humanos , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Escarro/microbiologia
19.
BMC Pediatr ; 20(1): 158, 2020 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-32284045

RESUMO

BACKGROUND: Recurrent bacterial infections of the respiratory tract are one of the major clinical features of the primary ciliary dyskinesia (PCD), a rare genetic disease due to malfunctioning of motile cilia. Chronic infections and persistent inflammation of the respiratory system result in progressive lung disease. Aim of the study was to highlight the main factors associated with clinical, functional and anatomical deterioration in PCD patients. METHODS: We retrospectively analyzed data from 58 patients with PCD, 37 adults and 21 children. The demographic and clinical data, forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC), sputum microbiology and imaging results (chest CT scores-modified Bhalla) were recorded. Patients were stratified according to the number of exacerbations (< 2/year vs ≥ 2/year) and chronic Pseudomonas aeruginosa (PA) colonization. The possible correlations between lung function and chest CT scores were assessed; we also evaluated the correlation between these parameters and the severity scores for bronchiectasis (BSI, FACED and e-FACED). RESULTS: Chest CT scores showed a significant correlation with FEV1 (p = 0.0002), age (p <  0.0001), BMI (p = 0.0002) and number of lung lobes involved (p <  0.0001). PA colonization had an overall prevalence of 32.6%: no significant difference in FEV1 between PA colonized and non-colonized patients was found (p = 0.70), while chest CT score was significantly worse in chronic PA colonized patients (p = 0.009). Patients with a high number of exacerbation (≥ 2/year) were older (p = 0.01), had lower FEV1 (p = 0.03), greater number of lobes involved (p < 0.001) and worse CT score than patients with low number of exacerbations (p = 0.001); they also had higher prevalence of PA chronic bronchial infection (33.3% versus 13.6%, p = 0.10). Multivariable linear regression analyses adjusted for gender, age and BMI showed positive associations between PA colonization and number of exacerbations with severity of disease (number of lobes involved, CT score, BSI, FACED, and e-FACED). CONCLUSIONS: In our PCD population the number of exacerbations (≥ 2/year) and PA colonization were the two most relevant factors associated with severity of disease.


Assuntos
Bronquiectasia , Transtornos da Motilidade Ciliar/patologia , Pulmão/patologia , Pseudomonas aeruginosa/isolamento & purificação , Adolescente , Adulto , Bronquiectasia/diagnóstico por imagem , Bronquiectasia/microbiologia , Criança , Transtornos da Motilidade Ciliar/microbiologia , Volume Expiratório Forçado , Humanos , Pulmão/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Exacerbação dos Sintomas , Adulto Jovem
20.
Am J Respir Crit Care Med ; 202(3): 433-447, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32320621

RESUMO

Rationale: Long-term antibiotic use for managing chronic respiratory disease is increasing; however, the role of the airway resistome and its relationship to host microbiomes remains unknown.Objectives: To evaluate airway resistomes and relate them to host and environmental microbiomes using ultradeep metagenomic shotgun sequencing.Methods: Airway specimens from 85 individuals with and without chronic respiratory disease (severe asthma, chronic obstructive pulmonary disease, and bronchiectasis) were subjected to metagenomic sequencing to an average depth exceeding 20 million reads. Respiratory and device-associated microbiomes were evaluated on the basis of taxonomical classification and functional annotation including the Comprehensive Antibiotic Resistance Database to determine airway resistomes. Co-occurrence networks of gene-microbe association were constructed to determine potential microbial sources of the airway resistome. Paired patient-inhaler metagenomes were compared (n = 31) to assess for the presence of airway-environment overlap in microbiomes and/or resistomes.Measurements and Main Results: Airway metagenomes exhibit taxonomic and metabolic diversity and distinct antimicrobial resistance patterns. A "core" airway resistome dominated by macrolide but with high prevalence of ß-lactam, fluoroquinolone, and tetracycline resistance genes exists and is independent of disease status or antibiotic exposure. Streptococcus and Actinomyces are key potential microbial reservoirs of macrolide resistance including the ermX, ermF, and msrD genes. Significant patient-inhaler overlap in airway microbiomes and their resistomes is identified where the latter may be a proxy for airway microbiome assessment in chronic respiratory disease.Conclusions: Metagenomic analysis of the airway reveals a core macrolide resistome harbored by the host microbiome.


Assuntos
Asma/microbiologia , Bronquiectasia/microbiologia , Farmacorresistência Bacteriana/genética , Disbiose/microbiologia , Macrolídeos , Metagenômica , Microbiota/genética , Doença Pulmonar Obstrutiva Crônica/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos , Estudos de Casos e Controles , Feminino , Fluoroquinolonas , Humanos , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores/microbiologia , Índice de Gravidade de Doença , Resistência a Tetraciclina/genética , Resistência beta-Lactâmica/genética
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