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1.
Mucosal Immunol ; 17(3): 461-475, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38184074

RESUMO

Tuberculosis is the leading cause of death for people living with HIV (PLWH). We hypothesized that altered functions of innate immune components in the human alveolar lining fluid of PLWH (HIV-ALF) drive susceptibility to Mycobacterium tuberculosis (M.tb) infection. Our results indicate a significant increase in oxidation of innate proteins and chemokine levels and significantly lower levels and function of complement components and Th1/Th2/Th17 cytokines in HIV-ALF versus control-ALF (non-HIV-infected people). We further found a deficiency of surfactant protein D (SP-D) and reduced binding of SP-D to M.tb that had been exposed to HIV-ALF. Primary human macrophages infected with M.tb exposed to HIV-ALF were significantly less capable of controlling the infection, which was reversed by SP-D replenishment in HIV-ALF. Thus, based on the limited number of participants in this study, our data suggest that PLWH without antiretroviral therapy (ART) have declining host innate defense function in their lung mucosa, thereby favoring M.tb and potentially other pulmonary infections.


Assuntos
Citocinas , Infecções por HIV , Imunidade Inata , Mycobacterium tuberculosis , Proteína D Associada a Surfactante Pulmonar , Humanos , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/fisiologia , Proteína D Associada a Surfactante Pulmonar/metabolismo , Proteína D Associada a Surfactante Pulmonar/imunologia , Infecções por HIV/imunologia , Citocinas/metabolismo , Masculino , Feminino , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo , Células Cultivadas , Adulto , Tuberculose Pulmonar/imunologia , Tuberculose/imunologia , Pessoa de Meia-Idade , Interações Hospedeiro-Patógeno/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Alvéolos Pulmonares/imunologia , Alvéolos Pulmonares/metabolismo
2.
AIDS ; 31(12): 1715-1720, 2017 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-28463881

RESUMO

OBJECTIVE: Lung cancer screening may benefit HIV-infected (HIV) smokers because of an elevated risk of lung cancer, but may have unique harms because of HIV-specific risk factors for false-positive screens. This study seeks to understand whether inflammatory biomarkers and markers of chronic lung disease are associated with noncalcified nodules at least 4 mm (NCN) in HIV compared with uninfected patients. DESIGN: This is a cohort study of Examinations of HIV-Associated Lung Emphysema (EXHALE), including 158 HIV and 133 HIV-uninfected participants. METHODS: Participants underwent a laboratory assessment [including measurement of D-dimer, interleukin 6, and soluble CD14 (sCD14)], chest computed tomography (CT), and pulmonary function testing. We created multivariable logistic regression models to determine predictors of NCN in the participants stratified by HIV status, with attention to semiqualitative scoring of radiographic emphysema, markers of pulmonary function, and inflammatory biomarkers. RESULTS: Of the 291 participants, 69 had NCN on chest CT. As previously reported, there was no difference in prevalence of these nodules by HIV status. Emphysema and elevated sCD14 demonstrated an association with NCN in HIV participants independent of smoking status, CD4 cell count, HIV viral load, and pulmonary function. CONCLUSION: Emphysema and sCD14, a marker of immune activation, was associated with a higher prevalence of NCN on chest CT in HIV participants. Patients with chronic immune activation and emphysema may be at higher risk for both false-positive findings and incident lung cancer, thus screening in this group requires further study to understand the balance of benefits and harms.


Assuntos
Detecção Precoce de Câncer/métodos , Enfisema/patologia , Infecções por HIV/complicações , Receptores de Lipopolissacarídeos/sangue , Neoplasias Pulmonares/diagnóstico por imagem , Pulmão/patologia , Tomografia Computadorizada por Raios X , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória
3.
Arch Intern Med ; 167(21): 2345-53, 2007 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-18039994

RESUMO

BACKGROUND: We sought to determine whether depressive or anxiety symptoms are associated with chronic obstructive pulmonary disease (COPD) hospitalization or mortality. These data were collected as part of the National Emphysema Treatment Trial (NETT), a randomized controlled trial of lung volume reduction surgery vs continued medical treatment conducted at 17 clinics across the United States between January 29, 1998, and July 31, 2002. METHODS: Prospective cohort study among participants in the NETT with emphysema and severe airflow limitation who were randomized to medical therapy. Primary outcomes were 1- and 3-year mortality, as well as COPD or respiratory-related hospitalization or emergency department visit during the 1-year follow-up period. Of 610 patients randomized to medical therapy, complete data on hospitalization and mortality were available for 3 years of follow-up for 603 patients (98.9%). RESULTS: Depressive symptoms were assessed using the Beck Depression Inventory (BDI) questionnaire, and anxiety was assessed using the State-Trait Anxiety Inventory. Among 610 subjects, 40.8% had at least mild to moderate depressive symptoms. Patients in the highest quintile of BDI score (BDI score, >or=15) had an increased risk of respiratory hospitalization in unadjusted analysis compared with patients in the lowest quintile (BDI score, < 5) (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.30-3.93). After adjustment for disease severity, this relationship was no longer statistically significant. The adjusted risk of 3-year mortality was increased among those in the highest quintile of BDI score (OR, 2.74; 95% CI, 1.42-5.29) compared with those in the lowest quintile. Anxiety was not associated with hospitalization or mortality in this population. CONCLUSIONS: Depressive symptoms are common in patients with severe COPD and are treated in few subjects. Depressive symptoms are associated with increased risk for 3-year mortality but not 1-year mortality or hospitalization.


Assuntos
Depressão/complicações , Hospitalização/estatística & dados numéricos , Doença Pulmonar Obstrutiva Crônica/cirurgia , Idoso , Antidepressivos/uso terapêutico , Depressão/diagnóstico , Depressão/tratamento farmacológico , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/mortalidade , Fatores de Risco , Fatores Sexuais , Taxa de Sobrevida , Estados Unidos
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