RESUMO
Alteration in microbiota composition of respiratory tract has been reported in the progression of many chronic lung diseases, yet, the correlation and causal link between respiratory tract microbiota and the disease development of pulmonary hypertension (PH) remain largely unknown. This study aims to define and compare the respiratory microbiota composition in pharyngeal swab samples between patients with PH and reference subjects. A total of 118 patients with PH and 79 reference subjects were recruited, and the pharyngeal swab samples were collected to sequence the 16S ribosomal RNA (16S rRNA) V3-V4 region of respiratory microbiome. The relative abundances in patients with PH were profoundly different from reference subjects. The Ace and Sobs indexes indicated that the microbiota richness of pharynx value is significantly higher; while the community diversity value is markedly lower in patients with PH, comparing to those of the reference subjects. The microbiota on pharynx showed a different profile between the 2 groups by principal component analysis. The linear discriminant analysis effect size also revealed a significantly higher proportion of Streptococcus, Lautropia, and Ralstonia in patients with PH than reference subjects. The linear discriminant analysis effect size output, which represents the microbial gene functions, suggest genes related to bacterial invasion of epithelial cells, bacterial toxins were enhanced, while genes related to energy metabolism, protein digestion and absorption, and cell division pathways were attenuated in patients with PH versus reference subjects. In summary, our study reports the first systematic definition and divergent profile of the upper respiratory tract microbiota between patients with PH and reference subjects.
Assuntos
Hipertensão Pulmonar/microbiologia , Microbiota/genética , Sistema Respiratório/microbiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genéticaRESUMO
Therapeutic advances for pulmonary hypertension (PH) have been incremental because of the focus on the pulmonary vasculature in PH pathology. Here, we evaluate the concept that PH is, rather, a systemic disorder involving interplay among multiorgan systems, including brain, gut, and lungs. Therefore, the objective of this study was to evaluate the hypothesis that PH is associated with a dysfunctional brain-gut-lung axis and that global overexpression of ACE2 (angiotensin-converting enzyme 2) rebalances this axis and protects against PH. ACE2 knockin and wild-type (WT; C57BL/6) mice were subjected to chronic hypoxia (10% FIO2) or room air for 4 weeks. Cardiopulmonary hemodynamics, histology, immunohistochemistry, and fecal 16S rRNA microbial gene analyses were evaluated. Hypoxia significantly increased right ventricular systolic pressure, sympathetic activity as well as the number and activation of microglia in the paraventricular nucleus of the hypothalamus in WT mice. This was associated with a significant increase in muscularis layer thickening and decreases in both villi length and goblet cells and altered gut microbiota. Global overexpression of ACE2 prevented changes in hypoxia-induced pulmonary and gut pathophysiology and established distinct microbial communities from WT hypoxia mice. Furthermore, WT mice subjected to fecal matter transfer from ACE2 knockin mice were resistant to hypoxia-induced PH compared with their controls receiving WT fecal matter transfer. These observations demonstrate that ACE2 ameliorates these hypoxia-induced pathologies and attenuates PH. The data implicate dysfunctional brain-gut-lung communication in PH and provide novel avenues for therapeutic interventions.
Assuntos
Enzima de Conversão de Angiotensina 2/fisiologia , Disbiose/etiologia , Microbioma Gastrointestinal , Hipertensão Pulmonar/microbiologia , Hipóxia/complicações , Enzima de Conversão de Angiotensina 2/genética , Animais , Disbiose/enzimologia , Disbiose/microbiologia , Disbiose/terapia , Transplante de Microbiota Fecal , Técnicas de Introdução de Genes , Hemodinâmica , Hipertensão Pulmonar/enzimologia , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/prevenção & controle , Hipertrofia Ventricular Direita/etiologia , Hipertrofia Ventricular Direita/prevenção & controle , Hipóxia/microbiologia , Inflamação , Pulmão/enzimologia , Pulmão/fisiopatologia , Camundongos , Microglia/patologia , Núcleo Hipotalâmico Paraventricular/patologia , Sistema Nervoso Simpático/fisiopatologiaRESUMO
BACKGROUND: Postnatal growth restriction (PNGR) in premature infants increases risk of pulmonary hypertension (PH). In a rodent model, PNGR causes PH, while combining PNGR and hyperoxia increases PH severity. We hypothesized that PNGR causes intestinal dysbiosis and that treatment with a probiotic attenuates PNGR-associated PH. METHOD: Pups were randomized at birth to room air or 75% oxygen (hyperoxia), to normal milk intake (10 pups/dam) or PNGR (17 pups/dam), and to probiotic Lactobacillus reuteri DSM 17938 or phosphate-buffered saline. After 14 days, PH was assessed by echocardiography and right ventricular hypertrophy (RVH) was assessed by Fulton's index (right ventricular weight/left ventricle + septal weight). The small bowel and cecum were analyzed by high-throughput 16S ribosomal RNA gene sequencing. RESULTS: PNGR with or without hyperoxia (but not hyperoxia alone) altered the microbiota of the distal small bowel and cecum. Treatment with DSM 17938 attenuated PH and RVH in pups with PNGR, but not hyperoxia alone. DSM 17938 treatment decreased α-diversity. The intestinal microbiota differed based on oxygen exposure, litter size, and probiotic treatment. CONCLUSION: PNGR causes intestinal dysbiosis and PH. Treatment with DSM 17938 prevents PNGR-associated RVH and PH. Changes in the developing intestine and intestinal microbiota impact the developing lung vasculature and RV.
Assuntos
Restrição Calórica/efeitos adversos , Ceco/microbiologia , Microbioma Gastrointestinal , Hipertensão Pulmonar/prevenção & controle , Intestino Delgado/microbiologia , Limosilactobacillus reuteri/fisiologia , Pulmão/irrigação sanguínea , Probióticos/administração & dosagem , Fenômenos Fisiológicos da Nutrição Animal , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Disbiose , Feminino , Hiperóxia/complicações , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/microbiologia , Hipertensão Pulmonar/fisiopatologia , Hipertrofia Ventricular Direita/etiologia , Hipertrofia Ventricular Direita/microbiologia , Hipertrofia Ventricular Direita/fisiopatologia , Hipertrofia Ventricular Direita/prevenção & controle , Tamanho da Ninhada de Vivíparos , Estado Nutricional , Gravidez , Ratos Sprague-DawleyRESUMO
We have analysed whether pulmonary arterial hypertension (PAH) alters the rat faecal microbiota. Wistar rats were injected with the VEGF receptor antagonist SU5416 (20 mg/kg s.c.) and followed for 2 weeks kept in hypoxia (10% O2, PAH) or injected with vehicle and kept in normoxia (controls). Faecal samples were obtained and microbiome composition was determined by 16S rRNA gene sequencing and bioinformatic analysis. No effect of PAH on the global microbiome was found (α- or ß-diversity). However, PAH-exposed rats showed gut dysbiosis as indicated by a taxonomy-based analysis. Specifically, PAH rats had a three-fold increase in Firmicutes-to-Bacteroidetes ratio. Within the Firmicutes phylum, there were no large changes in the relative abundance of the bacterial families in PAH. Among Bacteroidetes, all families were less abundant in PAH. A clear separation was observed between the control and PAH clusters based on short chain fatty acid producing bacterial genera. Moreover, acetate was reduced in the serum of PAH rats. In conclusion, faecal microbiota composition is altered as a result of PAH. This misbalanced bacterial ecosystem might in turn play a pathophysiological role in PAH by altering the immunologic, hormonal and metabolic homeostasis.
Assuntos
Microbioma Gastrointestinal/fisiologia , Hipertensão Pulmonar/microbiologia , Hipertensão Pulmonar/fisiopatologia , Animais , Biologia Computacional , Hemodinâmica/fisiologia , Masculino , RNA Ribossômico 16S/genética , Ratos , Ratos WistarRESUMO
RATIONALE: Pertussis has re-emerged on a global scale and is an ongoing public health problem, even in countries with high rates of vaccination. Hyperleukocytosis [white blood cell (WBC) count >100â×â10/L] is a rare complication that strongly predicts mortality in cases of severe pertussis. PATIENT CONCERNS: We report a case of severe pertussis in an infant who initially presented with persistent cyanotic cough, tachypnea, and grunting. The infant's condition deteriorated rapidly, and she was transferred to the pediatric intensive care unit (PICU) during her third hour of hospitalization. On the third hospital day, her WBC count had increased to 101.85â×â10/L with a lymphocyte count of 36.76â×â10/L, and her hemoglobin level had fallen to 6.9âg/dL. Bone marrow examination found no evidence of tumor cells. Her initial echocardiogram showed no abnormal findings; however, a subsequent echocardiogram 10 days later revealed pulmonary hypertension. DIAGNOSES: The patient was diagnosed with severe pneumonia, which was confirmed to be pertussis based on a persistent cough in the infant's mother and the polymerase chain reaction and culture of the infant's nasopharyngeal secretions being positive for Bordetella pertussis. INTERVENTIONS: The infant was treated with supportive care, early macrolide antibiotics, and broad-spectrum antibiotics before being transferred to the PICU for further management, including continuous venovenous hemodiafiltration. OUTCOMES: Unfortunately, the infant died as a result of pulmonary hypertension and multiorgan failure. LESSONS: Exchange transfusion should be considered in all infants who present with severe pertussis with hyperleukocytosis. This guideline is supported by the findings of a comprehensive literature review, which is included in this article, as well as newly published criteria for exchange transfusion therapy. Finally, we hope that adults in China will be vaccinated against B. pertussis in order to prevent the infection of infants within their households.
Assuntos
Hipertensão Pulmonar/microbiologia , Leucocitose/complicações , Insuficiência de Múltiplos Órgãos/microbiologia , Pneumonia Bacteriana/complicações , Coqueluche/complicações , China , Evolução Fatal , Feminino , Humanos , LactenteAssuntos
Receptores de Proteínas Morfogenéticas Ósseas Tipo II/imunologia , Hipertensão Pulmonar/imunologia , Intestinos/imunologia , Lipopolissacarídeos/toxicidade , Pulmão/imunologia , Receptor 4 Toll-Like/imunologia , Animais , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Humanos , Hipertensão Pulmonar/microbiologia , Hipertensão Pulmonar/patologia , Intestinos/microbiologia , Intestinos/patologia , Pulmão/microbiologia , Pulmão/patologia , Camundongos , Camundongos Mutantes , Receptor 4 Toll-Like/genéticaRESUMO
SETTING: Tertiary referral center, National Institutes of Health (NIH), USA. OBJECTIVE: To estimate the mortality rate and its correlates among persons with pulmonary non-tuberculous mycobacteria (PNTM) disease. DESIGN: A retrospective review of 106 patients who were treated at the NIH Clinical Center and met American Thoracic Society/Infectious Diseases Society of America criteria for PNTM. Eligible patients were aged ⩾18 years and did not have cystic fibrosis or human immunodeficiency virus (HIV) infection. RESULTS: Of 106 patients followed for a median of 4.9 years, 27 (25%) died during follow-up, for a mortality rate of 4.2 per 100 person-years. The population was predominantly female (88%) and White (88%), with infrequent comorbidities. Fibrocavitary disease (adjusted hazard ratio [aHR] 3.3, 95% confidence interval [CI] 1.3-8.3) and pulmonary hypertension (aHR 2.1, 95%CI 0.9-5.1) were associated with a significantly elevated risk of mortality in survival analysis. CONCLUSIONS: PNTM remains a serious public health concern, with a consistently elevated mortality rate across multiple populations. Significant risk factors for death include fibrocavitary disease and pulmonary hypertension. Further research is needed to more specifically identify clinical and microbiologic factors that jointly influence disease outcome.
Assuntos
Pulmão/microbiologia , Infecções por Mycobacterium não Tuberculosas/mortalidade , Micobactérias não Tuberculosas/isolamento & purificação , Infecções Respiratórias/mortalidade , Feminino , Humanos , Hipertensão Pulmonar/microbiologia , Hipertensão Pulmonar/mortalidade , Estimativa de Kaplan-Meier , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/diagnóstico por imagem , Infecções por Mycobacterium não Tuberculosas/microbiologia , National Institutes of Health (U.S.) , Micobactérias não Tuberculosas/classificação , Modelos de Riscos Proporcionais , Fibrose Pulmonar/microbiologia , Fibrose Pulmonar/mortalidade , Infecções Respiratórias/diagnóstico por imagem , Infecções Respiratórias/microbiologia , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária , Fatores de Tempo , Tomografia Computadorizada por Raios X , Estados Unidos/epidemiologiaRESUMO
INTRODUCTION: Non-tuberculous mycobacterial lung diseases (NTMLD) occur rarely and are diagnosed mainly in patients belonging to risk groups. Pulmonary hypertension (PH) has not been recognised as a risk factor for NTMLD yet. The aim of the study was to analyse the clinical course and predisposing factors of NTMLD recognised in our centre between 2002 and 2012 in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (IPAH). MATERIAL AND METHODS: Thirteen patients (10 - CTEPH, 3 - IPAH) entered the study. PH was recognised during right heart catheterisation. Median value of mean pulmonary artery pressure (mPAP) was 49 mm Hg (39-65 mm Hg). NTMLD was diagnosed according to ATS guidelines (2007). RESULTS: M. kansasii was the most frequent pathogen. Most patients complained of the exaggeration of dyspnoea and productive cough. Computed tomography of the chest with angiography revealed infiltrations with cavitation in seven patients and cavities surrounded by micronodules in six patients. In all CTEPH patients, NTMLD developed in the hypoperfused lung areas. No parenchymal abnormalities preceded the development of NTMLD. After diagnosis all of the patients received antituberculous treatment; in 12/13 improvement was achieved. By the end of March 2014 seven patients died due to right heart insufficiency, no deaths due to NTMLD were noted. CONCLUSIONS: NTMLD should be suspected in patients with CTEPH or IPAH, presenting with productive cough and a new pulmonary infiltrate with cavitation. In patients with CTEPH, special attention should be paid to a new cavitary lesions without accompanying thrombus in the artery supplying the area. High mPAP (CTEPH/IPAH) and hypoperfusion (CTEPH) are predisposing to NTMLD.
Assuntos
Hipertensão Pulmonar Primária Familiar/microbiologia , Hipertensão Pulmonar/microbiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Embolia Pulmonar/microbiologia , Hipertensão Pulmonar Primária Familiar/complicações , Hipertensão Pulmonar Primária Familiar/diagnóstico , Feminino , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Micobactérias não Tuberculosas/isolamento & purificação , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnósticoRESUMO
A 35-year-old man with a six-month history of progressive exertional dyspnea was referred to our institution. He had been diagnosed with Mycobacterium intracellulare pulmonary infection with lung cavitation two years earlier, and was being followed up without any medications. After being referred to our hospital, he underwent computed tomographic pulmonary angiography, which indicated a pulmonary thrombus and lung cavitation. Furthermore, right heart catheterization confirmed pulmonary hypertension, and we made a diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH). Following successful pulmonary endarterectomy, the patient's symptoms and hemodynamics were significantly improved, with the disappearance of lung cavitation. It is important to suspect CTEPH in patients with unaccountable infectious lung cavities.
Assuntos
Hipertensão Pulmonar/microbiologia , Infecção por Mycobacterium avium-intracellulare/complicações , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Embolia Pulmonar/microbiologia , Adulto , Endarterectomia , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/cirurgia , Masculino , Complexo Mycobacterium avium/isolamento & purificação , Infecção por Mycobacterium avium-intracellulare/cirurgia , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/cirurgiaRESUMO
Pulmonary hypertension (PH) is a disease of diverse etiology. Although primary PH can develop in the absence of prior disease, PH more commonly develops in conjunction with other pulmonary pathologies. We previously reported a mouse model in which PH occurs as a sequela of Pneumocystis infection in the context of transient CD4 depletion. Here, we report that instead of the expected Th2 pathways, the Th1 cytokine IFN-γ is essential for the development of PH, as wild-type mice developed PH but IFN-γ knockout mice did not. Because gene expression analysis showed few strain differences that were not immune-function related, we focused on those responses as potential pathologic mechanisms. In addition to dependence on IFN-γ, we found that when CD4 cells were continuously depleted, but infection was limited by antibiotic treatment, PH did not occur, confirming that CD4 T cells are required for PH development. Also, although CD8 T-cells are implicated in the pathology of Pneumocystis pneumonia, they did not have a role in the onset of PH. Finally, we found differences in immune cell phenotypes that correlated with PH, including elevated CD204 expression in lung CD11c(+) cells, but their role remains unclear. Overall, we demonstrate that a transient, localized, immune response requiring IFN-γ and CD4-T cells can disrupt pulmonary vascular function and promote lingering PH.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Hipertensão Pulmonar/imunologia , Hipertensão Pulmonar/microbiologia , Interferon gama/metabolismo , Pneumocystis/fisiologia , Animais , Líquido da Lavagem Broncoalveolar , Fibrose , Regulação da Expressão Gênica , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/patologia , Imunidade/genética , Imunofenotipagem , Interleucina-12/metabolismo , Depleção Linfocítica , Camundongos , Camundongos Knockout , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/genética , Pneumonia por Pneumocystis/imunologia , Pneumonia por Pneumocystis/patologia , Fator de Transcrição STAT6/deficiência , Fator de Transcrição STAT6/metabolismo , Receptores Depuradores Classe A/metabolismo , Regulação para CimaRESUMO
OBJECTIVE: Pertussis persists in the United States despite high immunization rates. This report characterizes the presentation and acute course of critical pertussis by quantifying demographic data, laboratory findings, clinical complications, and critical care therapies among children requiring admission to the PICU. DESIGN: Prospective cohort study. SETTING: Eight PICUs comprising the Eunice Kennedy Shriver National Institute for Child Health and Human Development Collaborative Pediatric Critical Care Research Network and 17 additional PICUs across the United States. PATIENTS: Eligible patients had laboratory confirmation of pertussis infection, were younger than 18 years old, and died in the PICU or were admitted to the PICU for at least 24 hours between June 2008 and August 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 127 patients were identified. Median age was 49 days, and 105 (83%) patients were less than 3 months old. Fifty-five (43%) patients required mechanical ventilation and 12 patients (9.4%) died during initial hospitalization. Pulmonary hypertension was found in 16 patients (12.5%) and was present in 75% of patients who died, compared with 6% of survivors (p < 0.001). Median WBC was significantly higher in those requiring mechanical ventilation (p < 0.001), those with pulmonary hypertension (p < 0.001), and nonsurvivors (p < 0.001). Age, sex, and immunization status did not differ between survivors and nonsurvivors. Fourteen patients received leukoreduction therapy (exchange transfusion [12], leukopheresis [1], or both [1]). Survival benefit was not apparent. CONCLUSIONS: Pulmonary hypertension may be associated with mortality in pertussis critical illness. Elevated WBC is associated with the need for mechanical ventilation, pulmonary hypertension, and mortality risk. Research is indicated to elucidate how pulmonary hypertension, immune responsiveness, and elevated WBC contribute to morbidity and mortality and whether leukoreduction might be efficacious.
Assuntos
Hipertensão Pulmonar/microbiologia , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Coqueluche/complicações , Coqueluche/mortalidade , Bradicardia/microbiologia , Transfusão Total , Feminino , Humanos , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/mortalidade , Lactente , Leucaférese , Contagem de Leucócitos , Masculino , Pneumonia/microbiologia , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Respiração Artificial , Taxa de Sobrevida , Estados Unidos/epidemiologia , Coqueluche/sangue , Coqueluche/terapiaRESUMO
Pulmonary endarterectomy (PEA) is a well-established procedure in the treatment of chronic thromboembolic pulmonary hypertension (CTPH). The procedure is known to increase functional outcome and to raise the 5-year survival rate. We report 2 cases of pulmonary valve endocarditis and secondary embolisms causing sustained pulmonary hypertension. Both were treated with PEA. In none of the cases, a cleavage between the thrombotic masses and the vessel wall was obtainable, and both attempts were therefore inadequate. Based on our reports, we recommend not attempting PEA in cases of CTPH after infectious embolisms.
Assuntos
Candidíase/cirurgia , Endarterectomia , Endocardite/cirurgia , Implante de Prótese de Valva Cardíaca , Hipertensão Pulmonar/cirurgia , Embolia Pulmonar/cirurgia , Valva Pulmonar/cirurgia , Adulto , Idoso , Candidíase/complicações , Candidíase/diagnóstico , Candidíase/microbiologia , Endocardite/complicações , Endocardite/diagnóstico , Endocardite/microbiologia , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/microbiologia , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/microbiologia , Valva Pulmonar/microbiologia , Resultado do TratamentoRESUMO
Adult hemophagocytic lymphohistiocytosis (HLH) is a rare and deadly hyperinflammatory syndrome presenting both diagnostic and therapeutic challenges. HLH may be primary, due to an underlying genetic abnormality, and/or secondary to infection, malignancy, or rheumatologic conditions. We describe a case of HLH-associated severe pulmonary hypertension paralleling Epstein-Barr virus (EBV) reactivation in a 52-year-old male in whom a novel perforin missense mutation was found (PRF1 1517C>T). Although intolerant of standard therapy (HLH-2004 protocol), a 6-week course of anti-CD52 (alemtuzumab) was associated with freedom-from-transfusion from weeks 4 to 13. However, 15 weeks after the onset of salvage therapy, he succumbed to polymicrobial sepsis despite treatment with prophylactic anti-infectives, with necropsy revealing disseminated blastomycosis and relapsed HLH. This case illustrates uncertainties in the relationships between pulmonary hypertension, a newly described PRF1 mutation, and possible pre-existing latent infectious risk factors (such as EBV or Blastomyces) in the pathogenesis and therapeutic perils of adult HLH.
Assuntos
Hipertensão Pulmonar/complicações , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/genética , Perforina/genética , Alemtuzumab , Anticorpos Monoclonais Humanizados/uso terapêutico , Blastomyces/isolamento & purificação , Blastomicose/complicações , Blastomicose/diagnóstico , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4/isolamento & purificação , Humanos , Hipertensão Pulmonar/microbiologia , Hipertensão Pulmonar/patologia , Pulmão/microbiologia , Pulmão/patologia , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/virologia , Masculino , Pessoa de Meia-Idade , Mutação de Sentido IncorretoRESUMO
A 3.5-week-old male neonate who developed an upper and lower respiratory tract rhinovirus infection that was temporally associated with the development of severe pulmonary hypertension is described. Rhinovirus has not previously been associated with pulmonary hypertension. This child developed severe pulmonary hypertension with right ventricular failure, requiring mechanical ventilation, nitric oxide inhalation and, eventually, extracorporeal membrane oxygenation.
Assuntos
Hipertensão Pulmonar/microbiologia , Infecções por Picornaviridae/complicações , Infecções Respiratórias/complicações , Rhinovirus , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/terapia , Recém-Nascido , Masculino , Infecções por Picornaviridae/diagnósticoRESUMO
OBJECTIVE: Group B Streptococcus is the most common cause of bacterial infection in the newborn. Our aim was to purify and identify molecules produced by the bacterium, which cause pulmonary hypertension. STUDY DESIGN: Guided by bioassays performed in neonatal lambs, we utilized standard biochemical techniques for the purification of these bioactive compounds. The compounds were identified by mass spectrometry. Fully synthetic compounds were then tested using the bioassay to confirm their ability to induce pulmonary hypertension. RESULT: The purified bacterial components causing pulmonary hypertension were the phospholipids cardiolipin and phosphatidylglycerol. Synthetic cardiolipin or phosphatidylglycerol also induced pulmonary hypertension in lambs. CONCLUSION: Bacterial phospholipids are capable of causing pulmonary hypertension. This finding opens new avenues for therapeutic intervention in persistent pulmonary hypertension of the newborn and generates hypotheses regarding the etiology of respiratory distress in the newborn and the possible effect of antibiotic therapy.
Assuntos
Cardiolipinas/fisiologia , Hipertensão Pulmonar/microbiologia , Fosfatidilgliceróis/fisiologia , Streptococcus agalactiae/metabolismo , Animais , Animais Recém-Nascidos , Cardiolipinas/biossíntese , Humanos , Hipertensão Pulmonar/fisiopatologia , Recém-Nascido , Espectrometria de Massas , Fosfatidilgliceróis/biossíntese , Ovinos , beta 2-Glicoproteína I/metabolismoRESUMO
Pertussis is ranked among the leading causes of childhood mortality. The most catastrophic clinical complication of pertussis in infants, intractable pulmonary hypertension with shock, is not very well known. We describe the clinical course of a fatal case of severe pertussis complicated by refractory pulmonary hypertension and shock in a 2-month-old infant.
Assuntos
Bordetella pertussis , Hipertensão Pulmonar/microbiologia , Gêmeos , Coqueluche/complicações , Antibacterianos/uso terapêutico , Bordetella pertussis/isolamento & purificação , Evolução Fatal , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/terapia , Lactente , Oxigênio/administração & dosagem , Resultado do Tratamento , Coqueluche/diagnóstico , Coqueluche/terapiaRESUMO
During the period 2002-2008, at the National Cardiovascular Center, Osaka, 28 Micrococcus luteus isolates and one Kocuria spp. isolate were obtained from blood cultures of pulmonary hypertension (PH) patients who were receiving continuous infusion therapy with epoprostenol. Pulsed-field gel electrophoresis patterns of the isolates were unrelated, suggesting that the infections had multiple origins. The preparation of epoprostenol solution by patients themselves was thought to be a risk factor.
Assuntos
Epoprostenol/administração & dosagem , Infecções por Bactérias Gram-Positivas/sangue , Infecções por Bactérias Gram-Positivas/microbiologia , Hipertensão Pulmonar/microbiologia , Micrococcus luteus/isolamento & purificação , Anti-Hipertensivos/administração & dosagem , Cateteres de Demora/microbiologia , Contaminação de Medicamentos , Eletroforese em Gel de Campo Pulsado , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/tratamento farmacológico , Infusões Intravenosas , Micrococcus luteus/genética , Inibidores da Agregação Plaquetária/administração & dosagemRESUMO
OBJECTIVES: To examine the relationship between chronic bacterial infection and pulmonary hypertension, using Doppler echocardiography, in patients with cystic fibrosis (CF). METHODS: A prospective cross-sectional study involving CF patients (>16 years of age) admitted to a program for adults with the disease. The study included 40 patients with a mean age of 23.7 +/- 6.3 years. Patients were submitted to clinical evaluation, Doppler echocardiography, pulmonary function tests, chest X-rays and sputum cultures of Pseudomonas aeruginosa and Burkholderia cepacia. RESULTS: In terms of the following variables, no significant differences were found between P. aeruginosa-positive patients and P. aeruginosa-negative patients: clinical score (p = 0.472); forced expiratory volume in one second (FEV1; p = 0.693), radiological score (p = 0.760); tricuspid regurgitant jet velocity (TRV, p = 0.330); diameter of the right ventricle (DRV, p = 0.191); and right ventricular/pulmonary artery (RV/PA) systolic acceleration time (SAT, p = 0.330). B. cepacia-positive patients presented significantly lower FEV1 than did B. cepacia-negative patients (p = 0.011). No significant differences were found between B. cepacia-positive patients and B. cepacia-negative patients regarding the following variables: clinical score (p = 0.080); radiological score (p = 0.760); TRV (p = 0.613); DRV (p = 0.429); and RV/PA SAT (p = 0.149). CONCLUSIONS: Chronic infection with P. aeruginosa or B. cepacia presented no association with pulmonary hypertension in adult CF patients. Pulmonary function was worse in B. cepacia-positive patients than in P. aeruginosa-positive patients.