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Bautista E.,National Institute of Respiratory Diseases | Chotpitayasunondh T.,Queen Sirikit National Institute of Child Health | Gao Z.,Peking University | Harper S.A.,Centers for Disease Control and Prevention | And 12 more authors.
New England Journal of Medicine | Year: 2010

As of March 2010, illness caused by the 2009 H1N1 virus had occurred in almost all countries, with more than 16,000 deaths from laboratory-confirmed cases reported to the World Health Organization (WHO). The United States saw an estimated 59 million pandemic H1N1 illnesses, 265,000 hospitalizations, and 12,000 deaths. This review by WHO experts summarizes the virologic, epidemiologic, and clinical data on the 2009 H1N1 virus and assesses future directions. Copyright © 2010 Massachusetts Medical Society.


Moreno-Coutino G.,National Institute of Respiratory Diseases | Arenas R.,Hospital Manuel Gea Gonzalez | Reyes-Teran G.,National Institute of Respiratory Diseases
International Journal of Dermatology | Year: 2013

Background Onychomycosis is frequent in patients with late and advanced HIV disease; immunocompromised patients may develop atypical clinical presentations that can be difficult to control. Current treatment for onychomycosis is based on the prolonged administration of antifungal therapies that may have significant interactions with combined antiretroviral therapy (cART). An improvement in certain HIV-associated opportunistic infections has been associated with initiation of cART. Objectives The aim of this study was to analyze the influence of cART on the outcome of onychomycosis in HIV-infected patients. Methods HIV-infected patients with dermatologic lesions attending the National Institute of Respiratory Diseases were asked to undergo physical examination. Detailed clinical histories were recorded. Routine laboratory tests, CD4 T cell count, and HIV viral load were performed. Onychomycosis was diagnosed on the basis of clinical appearance. Nail scrapings were collected from toenails and fingernails. Specimens were analyzed using direct microscopy. Nail changes after cART initiation were assessed by clinical examination. Results Improvement in onychomycosis was observed in six patients with late and advanced HIV disease after initiation of cART. Complete resolution of onychomycosis was observed in one patient without the use of antifungal therapy; one patient required topical antifungal treatment, and two patients required systemic antifungal treatment to achieve complete resolution. Conclusions Onychomycosis should be included in the group of pathologies that improve with cART-induced immune reconstitution. The pathogenesis of onychomycosis in HIV disease warrants investigation in the context of cell-mediated immunity restoration. © 2012 The International Society of Dermatology.


Sada-Ovalle I.,Harvard University | Sada-Ovalle I.,National Institute of Respiratory Diseases | Skold M.,Harvard University | Skold M.,Karolinska Institutet | And 3 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2010

Rationale: Invariant natural killer T (iNKT) cells are a unique subset of T cells that recognize lipid antigens presented by CD1d molecules. Recent studies have shown that iNKT cells can protect mice against Mycobacterium tuberculosis (Mtb) infection. We sought to determine whether pharmacological activation of iNKT cells by α-galactosylceramide (α-GalCer) could be used to treat tuberculosis (TB). Objectives: We hypothesized that α-GalCer, either alone or in combination with isoniazid, could be used to treat pulmonary TB. Methods: The ability of α-GalCer-activated iNKT cells to suppress Mtb replication was evaluated using an in vitro coculture system. To test its potency in vivo, mice infected with virulent Mtb were treated with α-GalCer alone or in combination with isoniazid. Measurements and Main Results: Quantitative colony-forming unit counts were compared for both experimental systems. Our results show that α-GalCer plus isoniazid controls bacterial growth better than α-GalCer or INH alone, and single or multiple α-GalCer administrations prolong the survival of the mice infected via the aerosol route. Conclusions: Our results demonstrate that α-GalCer administration can improve the outcome of Mtb infection, even when transmitted by the aerosol route. However, a combination of isoniazid and α-GalCer treatment has a synergistic effect on infection control. We conclude that more efficient treatment of TB will be achieved through a combination of classic chemotherapy and modulation of the host immune response.


Menezes A.M.B.,Federal University of Pelotas | De Oca M.M.,Central University of Venezuela | Perez-Padilla R.,National Institute of Respiratory Diseases | Nadeau G.,Glaxosmithkline | And 6 more authors.
Chest | Year: 2014

Background: Several COPD phenotypes have been described; the COPD-asthma overlap is one of the most recognized. The aim of this study was to evaluate the prevalence of three subgroups (asthma, COPD, and COPD-asthma overlap) in the Latin American Project for the Investigation of Obstructive Lung Disease (PLATINO) study population, to describe their main characteristics, and to determine the association of the COPD-asthma overlap group with exacerbations, hospitalizations, limitations due to physical health, and perception of general health status (GHS ). Methods: The PLATINO study is a multicenter population-based survey carried out in fi ve Latin American cities. Outcomes were self-reported exacerbations (defi ned by deterioration of breathing symptoms that affected usual daily activities or caused missed work), hospitalizations due to exacerbations, physical health limitations, and patients' perception of their GHS obtained by questionnaire. Subjects were classifi ed in three specifi c groups: COPD-a postbronchodilator (post-BD) FEV 1 /FVC ratio of , 0.70; asthma-presence of wheezing in the last year and a minimum post-BD increase in FEV 1 or FVC of 12% and 200 mL; and overlap COPD-asthma-the combination of the two. Results: Out of 5,044 subjects, 767 were classifi ed as having COPD (12%), asthma (1.7%), and COPD-asthma overlap (1.8%). Subjects with COPD-asthma overlap had more respiratory symptoms, had worse lung function, used more respiratory medication, had more hospitalization and exacerbations, and had worse GHS. After adjusting for confounders, the COPD-asthma overlap was associated with higher risks for exacerbations (prevalence ratio [PR], 2.11; 95% CI, 1.08-4.12), hospitalizations (PR, 4.11; 95% CI, 1.45-11.67), and worse GHS (PR, 1.47; 95% CI, 1.18-1.85) compared with those with COPD. Conclusions: The coexisting COPD-asthma phenotype is possibly associated with increased disease severity. © 2014 American College of Chest Physicians.


Cortes-Telles A.,National Institute of Respiratory Diseases | Mendoza-Posada D.,National Institute of Respiratory Diseases
Lung India | Year: 2012

Background: Mexico's National Institute of Respiratory Diseases (NIRD) is a third-level national reference center. Primary adenoid cystic carcinoma (PACC) is an uncommon neoplastic disorder; hence improvements in the description of this disease are needed. Materials and Methods: This is a retrospective clinical study based on all consecutive patients with pathological diagnoses of PACC seen at the NIRD between January 1, 2000 and December 31, 2009. Results: We identified 9 cases of PACC (67% female) out of a total of 2,634 patients with lung cancer seen during the period analyzed. The mean age of those 9 patients was 41 years (IQR 36-57), and the frequency of PACC at our center was 0.3%. It is important to note that 67% of those patients had a history of smoking and that 6 of the 9 had the antecedent of previous exposure to biomass fuel smoke. Baseline arterial blood gas analyses revealed a median of 61 mmHg for pO 2 and 28.5 mmHg for pCO 2. Median FVC was 78%, while FEV 1 was 77% with an FEV 1 /FVC ratio of 78. Death occurred in 56% of cases, and the median survival time was 17 months (IQR 6-26) after the initial diagnosis. Conclusions: The frequency of tracheobronchial PACC among patients with lung cancer was similar to that previously reported (0.3%). According to our results, lung function has no specific phenotype in this disease; however, some abnormalities could be related to potential risk factors such as tobacco use and exposure to biomass fuel smoke.


Sanchez-Jimenez R.,National Polytechnic Institute of Mexico | Alvarado-Vasquez N.,National Institute of Respiratory Diseases
Medical Hypotheses | Year: 2013

Diabetes mellitus type 2 (DM2), obesity, and the metabolic syndrome are considered that a low-grade chronic inflammatory condition. Although synthesis of different pro- and anti-inflammatory cytokines has been implicated in this process, this low-grade inflammatory condition is characterized especially by an increase in Tumor Necrosis Factor alpha (TNF-α), a cytokine that has been associated to the development of insulin resistance and muscle wasting in the diabetic patients. In consequence, mechanisms implicated in attenuating the deleterious effects of TNF-α are activated. One of these mechanisms may involve interleukin 15 (IL-15), which has proven effect on intermediate metabolisms, regulating blood glucose and lipid levels, and diminishing proteolysis in striated muscle. This suggests that the induction of endogenous IL-15 production by a simple event as physical activity may aid in decreasing or even inhibiting the negative effects of TNF-α in patient with DM2 or obesity, in which a low grade chronic inflammatory condition is present. © 2013 Elsevier Ltd.


Menezes A.M.B.,Federal University of Pelotas | Wehrmeister F.C.,Federal University of Pelotas | Hartwig F.P.,Federal University of Pelotas | Perez-Padilla R.,National Institute of Respiratory Diseases | And 5 more authors.
European Respiratory Journal | Year: 2015

African-Americans have smaller lung function compared with European-Americans. The aim of this study was to disentangle the contribution of genetics from other variables on lung function. A cohort was followed from birth to 30 years of age in Brazil. Several variables were collected: genomic analysis based on DNA; forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) obtained by spirometry; height measured by anthropometrists; and thorax circumference evaluated by photonic scanner. Crude and adjusted linear regression models were calculated according to African ancestry. The sample comprised 2869 participants out of 3701 members of the cohort. Males with higher African ancestry by DNA analysis had a smaller FEV1 (-0.13 L, 95% CI -0.23- -0.03 L) and FVC (-0.21 L, 95% CI -0.32- -0.09 L) compared with those with less African ancestry, having accounted for height, sitting to standing height ratio and other confounders. Similar effects were seen in females. After adjustment, ancestry remained significantly associated with lung function, but the large effect of adjustment for confounding among males (but not females) does not allow us to exclude the possibility that residual confounding may still account for these findings. Copyright ©ERS 2015.


Alcazar-Leyva S.,San Luis Potosí Institute of Scientific Research and Technology | Alvarado-Vasquez N.,National Institute of Respiratory Diseases
Medical Hypotheses | Year: 2011

Thiamine (Vitamin B1) is considered an essential micronutrient for humans; its deficient intake brings about the Wernicke-Korsakoff syndrome (encephalopathy and psychosis) or beriberi (a neurological and cardiovascular disease). Once thiamine enters the cells it is phosphorylated by thiamine pyrophosphokinase (TPPK), and converted into the coenzyme thiamine pyrophosphate (TPP), the active form of thiamine. TPP is a relevant cofactor for transketolase (TK), α-ketoglutarate dehydrogenase (αKDH), and pyruvate dehydrogenase (PDH), all these enzymes are fundamental for glucose metabolism. Diabetes mellitus (DM), however, is considered both a deficient thiamine and deficient energy state, as a consequence of the limited TPP synthesis. Recent evidences have shown that the administration of thiamine or lipid-soluble derivatives, such as benfotiamine (developed to improve the bioavailability of thiamine), has positive effects in the diabetic patient (after thiamine is transformed into TPP). For this reason, administration of supplements with TPP in the diabetic patients is recommended to avoid complications, like neuropathy and nephropathy. It has been suggested that these beneficial effects are a consequence of the activation of TK (pentose pathway) or the PDH complex in mitochondria. Nitric oxide (NO) is synthesized by the endothelial cell and is also an important element for the viability and functionality of this cell type. However, in the DM patient, a deficient synthesis of NO has been reported. It is relevant to mention that recent evidences have led to propose mitochondrial activity as an important regulator of nitric oxide synthesis (ON). We consider that the exogenous administration of TPP facilitates the utilization of this molecule, regulating some metabolic processes such as phosphorylation of thiamine by TPPK, energy consumption (ATP), as well as mitochondrial activity, inducing eventually NO synthesis. If this is confirmed, the administration of TPP to the diabetic patient would provide additional protection to endothelial cells, reducing the risk of vascular damage, to which the diabetic patient is highly susceptible. © 2011 Elsevier Ltd.


Prado-Garcia H.,National Institute of Respiratory Diseases | Romero-Garcia S.,National Institute of Respiratory Diseases | Rumbo-Nava U.,National Institute of Respiratory Diseases | Lopez-Gonzalez J.S.,National Institute of Respiratory Diseases
Anticancer Research | Year: 2015

Background: Regulatory T-(Treg) and proinflammatory T-helper 17 (Th17) cells have been reported to be involved in the pathogenesis of pleural effusions caused by lung cancer. However, the presence of these subsets might not be a consequence of tumor pathogenesis, but rather a result of the pleural effusion itself, irrespective of its origin. In the present study, we analyzed the balance between these CD4+ T-cell subsets and compared them with those in non-malignant pleural effusions. Patients and Methods: We detected the frequencies of Treg and Th17 cells, identified as cluster of differentiation (CD)3+CD4+CD25+CD127low/-and CD3+CD4+ retinoid-related orphan receptor t (ROR.t)+ cells respectively, and proportions of interleukin (IL)17Aproducing CD4+ cells in pleural effusions of patients with lung cancer, tuberculous and non-chronic pathologies by flow cytometry. The cytokine profile of stimulated CD4+ T-cells from tuberculosis and cancer groups was compared. Results: The proportion of Th17 cells were increased whereas Tregs were decreased in both tuberculosis and cancer, but not in non-chronic pathologies. Nevertheless, CD4+ T-cells from lung cancer effusions secreted interferon (IFN)., IL6 and IL17A, whereas CD4+ T-cells from tuberculous effusions secreted IL10 and low levels of IFN. Conclusion: Although effusions from patients with chronic pathologies presented higher proportions of Th17 cells in comparison to those with nonchronic pathologies, only Th17 cells from malignant effusions maintained their proinflammatory profile after stimulation. Thus, in the pleural compartment of patients with lung cancer, a proinflammatory environment might be favored and possibly maintained by Th17 response.


Jayaraman P.,Harvard University | Sada-Ovalle I.,Harvard University | Sada-Ovalle I.,National Institute of Respiratory Diseases | Beladi S.,Harvard University | And 5 more authors.
Journal of Experimental Medicine | Year: 2010

T cell immunoglobulin and mucin domain 3 (Tim3) is a negative regulatory molecule that inhibits effector TH1-type responses. Such inhibitory signals prevent unintended tissue inflammation, but can be detrimental if they lead to premature T cell exhaustion. Although the role of Tim3 in autoimmunity has been extensively studied, whether Tim3 regulates antimicrobial immunity has not been explored. Here, we show that Tim3 expressed on TH1 cells interacts with its ligand, galectin-9 (Gal9), which is expressed by Mycobacterium tuberculosis-infected macrophages to restrict intracellular bacterial growth. Tim3-Gal9 interaction leads to macrophage activation and stimulates bactericidal activity by inducing caspase-1-dependent IL-1β secretion. We propose that the TH1 cell surface molecule Tim3 has evolved to inhibit growth of intracellular pathogens via its ligand Gal9, which in turn inhibits expansion of effector TH1 cells to prevent further tissue inflammation. © 2010 Jayaraman et al.

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