Assuntos
Tórax em Funil/genética , Predisposição Genética para Doença , Prolapso da Valva Mitral/genética , Complexo Mycobacterium avium , Receptores Proteína Tirosina Quinases/genética , Escoliose/genética , Peso Corporal , Saúde da Família , Feminino , Tórax em Funil/complicações , Humanos , Interferon gama/metabolismo , Masculino , Prolapso da Valva Mitral/complicações , Mutação , Mutação de Sentido Incorreto , Infecção por Mycobacterium avium-intracellulare/complicações , Linhagem , Escoliose/complicações , SíndromeRESUMO
The household is a potential source of opportunistic pathogens to humans, a particularly critical issue for immunodeficient individuals. An important human-microbe interface is the biofilm that develops on showerhead surfaces. Once microbe-laden biofilms become aerosolized, they can potentially be inhaled into the lungs. Understanding how quickly a new showerhead becomes colonized would provide useful information to minimize exposure to potentially pathogenic environmental microbes. High school scientists sampled the inner surfaces of pre-existing and newly fitted showerheads monthly over a nine-month period and applied standard microbiologic culture techniques to qualitatively assess microbial growth. Water chemistry was also monitored using commercial test strips. Sampling was performed in households on Oahu, Hawai'i and Denver, Colorado, representing warm/humid and cold/arid environments, respectively. Pre-existing showerheads in Hawai'i showed more diverse microbial growth and significantly greater microbial numbers than a comparable showerhead from Colorado. New, chrome-plated or plastic showerheads in Hawai'i showed diverse and abundant growth one month after installment compared to new showerheads from Colorado. The pH, total chlorine and water hardness levels varied significantly between the Hawai'i and Colorado samples. Enthusiastic student and teacher participation allowed us to answer long-standing questions regarding the temporal colonization of microbial biofilms on pre-existing and new showerhead surfaces.
Assuntos
Bactérias/crescimento & desenvolvimento , Biodiversidade , Biofilmes/crescimento & desenvolvimento , Utensílios Domésticos , Bactérias/isolamento & purificação , Banhos , Pesquisa Biomédica/educação , Pesquisa Biomédica/métodos , Colorado , Havaí , Humanos , Umidade , Concentração de Íons de Hidrogênio , Ciência/educação , Estudantes , Fatores de Tempo , Água/químicaRESUMO
The geographic overlap between the prevalence of cigarette smoke (CS) exposure and tuberculosis (TB) in the world is striking. In recent years, relatively large number of studies has linked cigarette or biomass fuel smoke exposure and various aspects of TB. Our goals are to summarize the significance of the known published studies, graphically represent reports that quantified the association and discuss their potential limitations. PubMed searches were performed using the key words 'tuberculosis' with 'cigarette', 'tobacco', 'smoke' or 'biomass fuel smoke.' The references of relevant articles were examined for additional pertinent papers. A large number of mostly case-control and cross-sectional studies significantly associate both direct and second-hand smoke exposure with tuberculous infection, active TB, and/or more severe and lethal TB. Fewer link biomass fuel smoke exposure and TB. While a number of studies interpreted the association with multivariate analysis, other confounders are often not accounted for in these analyses. It is also important to emphasize that these retrospective studies can only show an association and not any causal link. We further explored the possibility that even if CS exposure is a risk factor for TB, several mechanisms may be responsible. Numerous studies associate cigarette and biomass smoke exposure with TB but the mechanism(s) remains largely unknown. While the associative link of these two health maladies is well established, more definitive, mechanistic studies are needed to cement the effect of smoke exposure on TB pathogenesis and to utilize this knowledge in empowering public health policies.
Assuntos
Exposição Ambiental/estatística & dados numéricos , Tuberculose Latente/epidemiologia , Fumaça , Fumar/epidemiologia , Tuberculose Pulmonar/epidemiologia , Biomassa , Fontes Geradoras de Energia/estatística & dados numéricos , Humanos , Prevalência , Fatores de Risco , Produtos do Tabaco , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Tuberculose/epidemiologiaAssuntos
Síndrome de Guillain-Barré/etiologia , Tuberculose Pulmonar/complicações , Adulto , Diagnóstico Diferencial , Eletrocardiografia , Seguimentos , Síndrome de Guillain-Barré/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Masculino , Radiografia Torácica , Tuberculose Pulmonar/diagnósticoRESUMO
We previously found that a subset of patients with pulmonary non-tuberculous mycobacterial (pNTM) disease were taller, leaner, and had a higher prevalence of pectus excavatum and scoliosis than uninfected controls. Additionally, whole blood of pNTM patients stimulated ex vivo with live Mycobacterium intracellulare produced significantly less interferon-gamma (IFNγ) compared to that of uninfected controls. Since IFNγ production can be suppressed by transforming growth factor-beta (TGFß), an immunosuppressive cytokine, we measured basal and M. intracellulare-stimulated blood levels of TGFß in a group of 20 pNTM patients and 20 uninfected controls. In contrast to the IFNγ findings, we found that stimulated blood from pNTM patients produced significantly higher levels of TGFß compared to controls. Since pNTM patients frequently possess body features that overlap with Marfan syndrome (MFS), and increased TGFß expression is important in the pathogenesis of MFS, we posit that a yet-to-be-identified syndrome related to MFS predisposes certain individuals to develop pNTM disease.
Assuntos
Pneumopatias/sangue , Infecções por Mycobacterium não Tuberculosas/sangue , Complexo Mycobacterium avium/isolamento & purificação , Fator de Crescimento Transformador beta/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Fibrilinas , Humanos , Pneumopatias/microbiologia , Síndrome de Marfan , Proteínas dos Microfilamentos/sangue , Infecções por Mycobacterium não Tuberculosas/microbiologiaRESUMO
The incidence of lung and other diseases due to nontuberculous mycobacteria (NTM) is increasing. NTM sources include potable water, especially in households where NTM populate pipes, taps, and showerheads. NTM share habitats with free-living amoebae (FLA) and can grow in FLA as parasites or as endosymbionts. FLA containing NTM may form cysts that protect mycobacteria from disinfectants and antibiotics. We first assessed the presence of FLA and NTM in water and biofilm samples collected from a hospital, confirming the high prevalence of NTM and FLA in potable water systems, particularly in biofilms. Acanthamoeba spp. (genotype T4) were mainly recovered (8/17), followed by Hartmannella vermiformis (7/17) as well as one isolate closely related to the genus Flamella and one isolate only distantly related to previously described species. Concerning mycobacteria, Mycobacterium gordonae was the most frequently found isolate (9/17), followed by Mycobacterium peregrinum (4/17), Mycobacterium chelonae (2/17), Mycobacterium mucogenicum (1/17), and Mycobacterium avium (1/17). The propensity of Mycobacterium avium hospital isolate H87 and M. avium collection strain 104 to survive and replicate within various FLA was also evaluated, demonstrating survival of both strains in all amoebal species tested but high replication rates only in Acanthamoeba lenticulata. As A. lenticulata was frequently recovered from environmental samples, including drinking water samples, these results could have important consequences for the ecology of M. avium in drinking water networks and the epidemiology of disease due to this species.
Assuntos
Acanthamoeba/microbiologia , Biofilmes , Mycobacterium avium/crescimento & desenvolvimento , Micobactérias não Tuberculosas/isolamento & purificação , Microbiologia da Água , Abastecimento de Água , Acanthamoeba/isolamento & purificação , Técnicas de Cocultura , Água Potável/microbiologia , Água Potável/parasitologia , Ecossistema , Hartmannella/isolamento & purificação , Hartmannella/microbiologia , Hospitais , Viabilidade Microbiana , Mycobacterium avium/isolamento & purificação , Micobactérias não Tuberculosas/crescimento & desenvolvimentoRESUMO
Nontuberculous mycobacteria (NTM) are environmental microbes that cause a variety of human diseases, particularly chronic lung infections. Despite the fact that NTM are widespread in the environment, relatively few people develop NTM lung disease, suggesting intrinsic vulnerability in some individuals. This paper reviews the evidence that underlying disorders predispose to NTM lung disease, in particular primary conditions that result in bronchiectasis, chronic obstructive pulmonary disease, α-1-antitrypsin anomalies, pneumoconiosis, pulmonary alveolar proteinosis, and frank immunosuppressive states such as that associated with the use of anti-tumor necrosis factor-α biologics, posttransplantation immunosuppression, and HIV infection. Over the past several decades, NTM lung disease has been increasingly identified in postmenopausal women with slender body habitus. Thus we will also review the clinical and experimental evidence which supports the observation that such individuals are predisposed to NTM lung disease.
Assuntos
Pneumopatias/epidemiologia , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Micobactérias não Tuberculosas/isolamento & purificação , Animais , Feminino , Humanos , Pneumopatias/etiologia , Pneumopatias/microbiologia , Masculino , Infecções por Mycobacterium não Tuberculosas/etiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Pós-Menopausa , Fatores de RiscoRESUMO
RATIONALE: Among patients with nontuberculous mycobacterial lung disease is a subset of previously healthy women with a slender body morphotype, often with scoliosis and/or pectus excavatum. We hypothesize that unidentified factors predispose these individuals to pulmonary nontuberculous mycobacterial disease. OBJECTIVES: To compare body morphotype, serum adipokine levels, and whole-blood cytokine responses of patients with pulmonary nontuberculous mycobacteria (pNTM) with contemporary control subjects who are well matched demographically. METHODS: We enrolled 103 patients with pNTM and 101 uninfected control subjects of similar demographics. Body mass index and body fat were quantified. All patients with pNTM and a subset of control subjects were evaluated for scoliosis and pectus excavatum. Serum leptin and adiponectin were measured. Specific cytokines important to host-defense against mycobacteria were measured in whole blood before and after stimulation. MEASUREMENTS AND MAIN RESULTS: Patients with pNTM and control subjects were well matched for age, gender, and race. Patients with pNTM had significantly lower body mass index and body fat and were significantly taller than control subjects. Scoliosis and pectus excavatum were significantly more prevalent in patients with pNTM. The normal relationships between the adipokines and body fat were lost in the patients with pNTM, a novel finding. IFN-γ and IL-10 levels were significantly suppressed in stimulated whole blood of patients with pNTM. CONCLUSIONS: This is the first study to comprehensively compare body morphotype, adipokines, and cytokine responses between patients with NTM lung disease and demographically matched controls. Our findings suggest a novel, predisposing immunophenotype that should be mechanistically defined.
Assuntos
Infecções por Mycobacterium não Tuberculosas/etiologia , Adipocinas/sangue , Tecido Adiposo/fisiologia , Índice de Massa Corporal , Estudos de Casos e Controles , Citocinas/sangue , Suscetibilidade a Doenças/sangue , Suscetibilidade a Doenças/imunologia , Feminino , Tórax em Funil/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/imunologia , Fenótipo , Escoliose/complicaçõesRESUMO
BACKGROUND: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB. METHODS AND FINDINGS: Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95% CI 1.1-6.0]), ofloxacin (aOR: 2.5 [1.6-3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3-2.3]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 [1.3-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 2.7 [1.7-4.1]). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 [1.7-4.3]), ofloxacin (aOR: 2.3 [1.3-3.8]), ethionamide or prothionamide (aOR: 1.7 [1.4-2.1]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 [1.9-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 4.5 [3.4-6.0]). CONCLUSIONS: In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment. Please see later in the article for the Editors' Summary.
Assuntos
Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Intervalos de Confiança , Feminino , Humanos , Masculino , Razão de Chances , Recidiva , Falha de TratamentoRESUMO
The purpose of this article is to update specialists in pulmonary medicine on the role of surgical resection and lung transplantation for bronchiectasis. The focus is on pre-operative workup, the technical details of surgical resection, complications, and outcomes.
Assuntos
Bronquiectasia/cirurgia , Transplante de Pulmão , Pneumonectomia , Humanos , Transplante de Pulmão/efeitos adversos , Transplante de Pulmão/métodos , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Cuidados Pós-Operatórios , Guias de Prática Clínica como Assunto , Cuidados Pré-Operatórios , Resultado do TratamentoRESUMO
Phylogenetic analyses on the basis of multiple house-keeping genes and whole genome sequences have offered new insights in the phylogeny of the genus Mycobacterium. This genus yields obligate pathogens, the M. tuberculosis complex and M. leprae, as well as opportunistic pathogens (e.g. M. avium, M. intracellulare, M. kansasii, M. marinum, M. malmoense) and saprophytes (e.g. M. phlei, M. sphagni, M. gordonae). The most virulent mycobacteria, the M. tuberculosis complex, M. leprae and the M. kansasii-M. szulgai-M. marinum-M. ulcerans group are phylogenetically related and infections by these organisms are better treatable than those caused by less virulent and phylogenetically more distantly related Mycobacterium species. The most virulent Mycobacterium species are also characterized by high levels of natural drug susceptibility. In this paper, we review studies of phylogeny, drug susceptibility, and clinical significance to support our hypothesis that drug susceptibility in mycobacteria is acquired and reflects the low level of competition in -and adaptation to- a closer-to-human (environmental) niche. In turn, mycobacteria that inhabit the most competitive environmental niches are the least adapted to humans, thus of low clinical significance, but most tolerant to antibiotics derived from microbes with which they share their habitat, lowering the chances of cure in case of infection.
Assuntos
Antituberculosos/uso terapêutico , Infecções por Mycobacterium/tratamento farmacológico , Mycobacterium/genética , Mycobacterium/patogenicidade , Filogenia , Humanos , Mycobacterium/classificação , Resultado do Tratamento , Virulência/genéticaRESUMO
Patients with rheumatologic disease are at increased risk for mycobacterial infections because of both immunocompromising therapy and preexisting lung damage from the disease itself. Tuberculosis is uncommon in the United States; however, it is relatively more prevalent in immigrants, minorities, elderly, persons with acquired immune deficiency syndrome and among healthcare workers. In the United States, the nontuberculous mycobacteria (NTM) are now more prevalent than tuberculosis. Although initially noted in men with chronic obstructive pulmonary disease, recent observations indicate increasing numbers of NTM cases in slender white women. Because of the often atypical presentation of NTM lung disease, diagnosis is commonly delayed. Because there is solid evidence that tumor necrosis factor-alpha-modifying agents are associated with serious NTM disease, it is important that specific screening tests (eg, chest x-ray, computed tomographic lung scans, sputum cultures or referral to pulmonary or infectious disease specialists) be used before initiating anti-tumor necrosis factor therapy.
Assuntos
Pneumopatias/epidemiologia , Pneumopatias/microbiologia , Infecções por Mycobacterium/epidemiologia , Doenças Reumáticas/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Antituberculosos/uso terapêutico , Etanercepte , Testes Genéticos , Humanos , Imunoglobulina G/efeitos adversos , Imunoglobulina G/uso terapêutico , Infliximab , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Prevalência , Receptores do Fator de Necrose Tumoral/uso terapêutico , Fatores de RiscoRESUMO
BACKGROUND: Cigarette smoke (CS) exposure is an epidemiological risk factor for tuberculosis, although the biological basis has not been elucidated. METHODS: We exposed C57BL/6 mice to CS for 14 weeks and examined their ability to control an aerosol infection of Mycobacterium tuberculosis Erdman. RESULTS: CS-exposed mice had more M. tuberculosis isolated from the lungs and spleens after 14 and 30 d, compared with control mice. The CS-exposed mice had worse lung lesions and less lung and splenic macrophages and dendritic cells (DCs) producing interleukin12 and tumor necrosis factor α (TNF-α). There were significantly more interleukin 10-producing macrophages and DCs in the spleens of infected CS-exposed mice than in non-CS-exposed controls. CS-exposed mice also showed a diminished influx of interferon γ-producing and TNF-α-producing CD4(+) and CD8(+) effector and memory T cells into the lungs and spleens. There was a trend toward an increased number of viable intracellular M. tuberculosis in macrophages isolated from humans who smoke compared with nonsmokers. THP-1 human macrophages and primary human alveolar macrophages exposed to CS extract, nicotine, or acrolein showed an increased burden of intracellular M. tuberculosis. CONCLUSION: CS suppresses the protective immune response to M. tuberculosis in mice, human THP-1 cells, and primary human alveolar macrophages.
Assuntos
Suscetibilidade a Doenças , Mycobacterium tuberculosis/imunologia , Fumar/efeitos adversos , Tuberculose/imunologia , Animais , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos C57BLAssuntos
Antituberculosos/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/epidemiologia , Seleção de Pacientes , Fumar/epidemiologia , Adolescente , Adulto , Comorbidade , Exposição Ambiental/prevenção & controle , Feminino , Saúde Global , Humanos , Masculino , Fatores de Risco , Fumar/efeitos adversos , Prevenção do Hábito de Fumar , Poluição por Fumaça de Tabaco/efeitos adversos , Tuberculose/prevenção & controleRESUMO
RATIONALE: Long-term survivors of cystic fibrosis (CF) (age > 40 yr) are a growing population comprising both patients diagnosed with classic manifestations in childhood, and nonclassic phenotypes typically diagnosed as adults. Little is known concerning disease progression and outcomes in these cohorts. OBJECTIVES: Examine effects of age at diagnosis and gender on disease progression, setting of care, response to treatment, and mortality in long-term survivors of CF. METHODS: Retrospective analysis of the Colorado CF Database (1992-2008), CF Foundation Registry (1992-2007), and Multiple Cause of Death Index (1992-2005). MEASUREMENTS AND MAIN RESULTS: Patients with CF diagnosed in childhood and who survive to age 40 years have more severe CFTR genotypes and phenotypes compared with adult-diagnosed patients. However, past the age of 40 years the rate of FEV(1) decline and death from respiratory complications were not different between these cohorts. Compared with males, childhood-diagnosed females were less likely to reach age 40 years, experienced faster FEV(1) declines, and no survival advantage. Females comprised the majority of adult-diagnosed patients, and demonstrated equal FEV(1) decline and longer survival than males, despite a later age at diagnosis. Most adult-diagnosed patients were not followed at CF centers, and with increasing age a smaller percentage of CF deaths appeared in the Cystic Fibrosis Foundation Registry. However, newly diagnosed adults demonstrated sustained FEV(1) improvement in response to CF center care. CONCLUSIONS: For patients with CF older than 40 years, the adult diagnosis correlates with delayed but equally severe pulmonary disease. A gender-associated disadvantage remains for females diagnosed in childhood, but is not present for adult-diagnosed females.
Assuntos
Fibrose Cística/diagnóstico , Sobreviventes/estatística & dados numéricos , Adulto , Distribuição por Idade , Idade de Início , Idoso , Colorado/epidemiologia , Fibrose Cística/complicações , Fibrose Cística/epidemiologia , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Sistema de Registros , Estudos Retrospectivos , Índice de Gravidade de Doença , Distribuição por SexoRESUMO
BACKGROUND: Nontuberculous mycobacteria (NTM) are environmental microbes that are associated with a variety of human diseases, particularly chronic lung infections. Over the past several decades, NTM lung disease has been increasingly seen in postmenopausal women with slender body habitus. OBJECTIVE: This article reviewed the clinical and experimental evidence that supports the observation that thin older women (aged 50-80 years) are predisposed to NTM lung disease. We posited 3 potential pathways for this predisposition: relative estrogen deficiency, abnormal levels of adipokines that alter immune responses, and abnormal expression of transforming growth factor-beta (TGF-beta) related to fibrillin anomalies similar to Marfan syndrome (MFS). METHODS: Using the PubMed database, a literature search was performed (all publications up to July 2009) by pairing the key phrase nontuberculous mycobacteria with weight, malnutrition, female gender, body habitus, leptin, adipokines, estrogen, menopause, postmenopausal, or body mass index. Non-English-language articles were included if their abstracts were in English. Relevant articles were also identified from the abstracts. RESULTS: Published case reports and series indicate that in the past 20 years, NTM lung disease has been recognized in disproportionately increased numbers in postmenopausal women. Among these patients, slender body habitus and thoracic cage abnormalities, such as pectus excavatum and scoliosis, are commonly described. Notably, no long-term prospective clinical studies exist to corroborate that low weight is an independent risk factor for NTM lung disease. However, based on the findings of a limited number of experimental studies, we hypothesize that decreased leptin, increased adiponectin, and/or decreased estrogen in older women with slender body habitus may account for their increased susceptibility to NTM infections. We further speculate that in some patients with features mindful of MPS (slender, scoliosis, pectus excavatum, or mitral valve prolapse), there may be anomalies of fibrillin, similar to MFS, that lead to the expression of the immunosuppressive cytokine TGP-beta further increasing their susceptibility to NTM. CONCLUSIONS: It is likely that both sufficient environmental exposure and host susceptibility are required for the establishment of NTM lung disease. The observation that NTM lung infections are more common in slender, older women without any overt immune defects suggests that abnormal expression of adipokines, sex hormones, and/or TGF-beta may play an important role in their susceptibility.
Assuntos
Pneumopatias/microbiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Magreza , Idoso , Idoso de 80 Anos ou mais , Suscetibilidade a Doenças/imunologia , Suscetibilidade a Doenças/microbiologia , Estrogênios/imunologia , Feminino , Fibrilinas , Humanos , Leptina/imunologia , Proteínas dos Microfilamentos/fisiologia , Pessoa de Meia-Idade , Pós-MenopausaRESUMO
Multidrug-resistant tuberculosis (TB) strains resistant to the fluoroquinolones and streptomycin but susceptible to second-line injection treatment would not be defined as extensively drug-resistant TB. In a cohort of 174 patients with multidrug-resistant TB, we demonstrated that 12 patients with multidrug-resistant TB strains resistant to the fluoroquinolones and streptomycin had significantly better initial and long-term outcomes, compared with 10 patients with extensively drug-resistant TB.