Fatal malignant pertussis with hyperleukocytosis in a Chinese infant: A case report and literature review.

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 >100 × 10/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 101.85 × 10/L with a lymphocyte count of 36.76 × 10/L, and her hemoglobin level had fallen to 6.9 g/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.

Mortality among patients with pulmonary non-tuberculous mycobacteria disease.

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.

Pulmonary endarterectomy after pulmonary infectious embolisms.

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.

Adult hemophagocytic lymphohistiocytosis with severe pulmonary hypertension and a novel perforin gene mutation.

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.

[Chronic bacterial infection and echocardiographic parameters indicative of pulmonary hypertension in patients with cystic fibrosis]. / Infecção bacteriana crônica e indicadores ecocardiográficos de hipertensão pulmonar em pacientes com fibrose cística.

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.

Guidelines for the prevention of central venous catheter-related blood stream infections with prostanoid therapy for pulmonary arterial hypertension.

Intravenous prostanoids are the backbone of therapy for advanced pulmonary arterial hypertension (PAH) and have improved long-term outcome and quality of life. Currently, two prostanoids are approved by the US Food and Drug administration for parenteral administration: epoprostenol (Flolan) and treprostinil (Remodulin). Chronic intravenous therapy presents considerable challenges for patients and caregivers who must learn sterile preparation of the medication, operation of the pump, and care of the central venous catheter. Patients are routinely counseled and advised regarding the risks of CR-BSIs and catheter care before central line insertion. Central line infections as well as bacteremia are well documented risks of chronic intravenous therapy and may significantly contribute to morbidity and mortality. Recent reports have suggested a possible increase in CR-BSI; therefore, the Scientific Leadership Council of the Pulmonary Hypertension Association decided to provide guidelines for good clinical practice regarding catheter care. Although data exits regarding patients with central venous catheters and the risk of blood stream infections in patients with cancer or other disorders, there is little data regarding the special needs of patients with pulmonary arterial hypertension requiring central venous access. These guidelines are extrapolated from the diverse body of literature regarding central venous catheter care.

Infecção bacteriana crônica e indicadores ecocardiográficos de hipertensão pulmonar em pacientes com fibrose cística / Chronic bacterial infection and echocardiographic parameters indicative of pulmonary hypertension in patients with cystic fibrosis

OBJETIVO: Determinar as relações entre infecção bacteriana crônica e hipertensão pulmonar, avaliada por ecocardiografia Doppler, em pacientes com fibrose cística (FC). MÉTODOS: Estudo transversal e prospectivo em pacientes com FC (idade > 16 anos) atendidos por um programa para adultos com a doença. O estudo incluiu 40 pacientes com média de idade de 23,7 ± 6,3 anos. Os pacientes foram submetidos a avaliação clínica, ecocardiografia Doppler, testes de função pulmonar, exame radiológico do tórax e exames culturais do escarro de Pseudomonas aeruginosa e Burkholderia cepacia. RESULTADOS: Não foram observadas diferenças entre os casos positivos para P. aeruginosa e os negativos para P. aeruginosa quanto às seguintes variáveis: escore clínico (p = 0,472); volume expiratório forçado no primeiro segundo (VEF1; p = 0,693); escore radiológico (p = 0,760); velocidade de regurgitação tricúspide (VRT, p = 0,330); diâmetro do ventrículo direito (DVD, p = 0,191); e tempo de aceleração sistólica (TAS) do ventrículo direito/artéria pulmonar (VD/AP, p = 0,330). O VEF1 foi significativamente menor nos casos positivos para B. cepacia do que nos casos negativos para B. cepacia (p = 0,011). Não foram observadas diferenças entre os casos positivos para B. cepacia e os casos negativos para B. cepacia quanto às seguintes variáveis: escore clínico (p = 0,080); escore radiológico (p = 0,760); VRT (p = 0,613); DVD (p = 0,429); e TAS do VD/AP (p = 0,149). CONCLUSÕES: Não foi observada relação entre infecção crônica por P. aeruginosa e por B. cepacia com hipertensão pulmonar em pacientes adultos com FC. A função pulmonar foi pior nos pacientes positivos para B. cepacia do que nos pacientes positivos para P. aeruginosa.

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.

Coqueluche grave con hipertensión pulmonar tratado con exanguineotransfusión / Severe Pertussis with pulmonary hypertension: cardiorespiratory improvement after exchange transfusion

Introducción: La infección grave causada por Bordetella pertussis en la infancia produce una alta mortalidad, a pesar del uso de soporte vital avanzado. Su mal pronóstico está ligado al desarrollo de hipertensión pulmonar refractaria, cuya etiopatogenia es pobremente entendida. La presencia de hiperleucocitosis en estos niños es un factor de riesgo conocido para la génesis de hipertensión pulmonar, sugiriéndose recientemente el empleo de terapias cito reductoras, entre ellas la exanguineotransfusión. Caso clínico: Comunicamos una lactante de 4 meses de edad, no vacunada que ingresa por coqueluche, con marcado compromiso de intercambio gaseoso, shock cardiogénico e hipertensión pulmonar grave asociados a leucocitosis de 78,800/µl. Ante fracaso de la terapia habitual se decide realizar exanguineotransfusiones, obteniéndose una buena respuesta hemodinámica y de intercambio gaseoso, temporalmente asociadas a la terapia, inexplicable por el curso natural de la enfermedad. Conclusión: El caso presentado sugiere que la exanguineotransfusión precoz puede ser una terapia útil en el tratamiento del coqueluche grave con hiperleucocitosis.

De novo pulmonary capillary hemangiomatosis occurring rapidly after bilateral lung transplantation.

A 45-year-old woman experienced diffuse bilateral pulmonary capillary hemangiomatosis within 3 months after bilateral lung transplantation. The donor was a 41-year-old man with excellent lung function and without histologic or macroscopic pulmonary lesions at the time of retrieval. This case supports the theory that persistent infection or inflammation may be an inciting factor in uncontrolled angiogenesis, leading ultimately to diffuse pulmonary capillary hemangiomatosis.

Platelet-activating factor and arachidonic acid metabolites mediate tumor necrosis factor and eicosanoid kinetics and cardiopulmonary dysfunction during bacteremic shock.

OBJECTIVE: Platelet-activating factor (PAF) and eicosanoids are putative mediators of septic shock that are associated with release of tumor necrosis factor (TNF). The purpose of this investigation was to a) examine temporal patterns of TNF and arachidonic acid metabolite release in a porcine model of bacteremic shock and b) selectively block PAF, thromboxane A2, prostacyclin, and leukotrienes to determine the relationships among these inflammatory response mediators and the alterations in cardiorespiratory dysfunction for which they are required. DESIGN: Prospective, nonrandomized, controlled trial. SETTING: Laboratory at a university medical center. SUBJECTS: Thirty-four female Yorkshire swine. INTERVENTIONS: Animals were divided into six experimental groups: five septic groups receiving an infusion of Aeromonas hydrophila at 0.2 mL/kg/hr, gradually increasing to 0.4 mL/kg/hr over 4 hrs. Each of four septic groups was pretreated with a specific mediator inhibitor (PAF receptor antagonist, n = 6; prostacyclin antibody, n = 5; leukotriene synthesis inhibitor, n = 5; and thromboxane receptor antagonist, n = 6). One septic group (n = 6) received no mediator inhibitor and served as a septic control, and one anesthesia control group (n = 6) received no intervention. MEASUREMENTS AND MAIN RESULTS: PAF receptor blockade significantly increased systemic hypotension and mixed venous oxygen saturation and decreased pulmonary artery pressure, oxygen extraction and consumption, hemoconcentration, and levels of TNF and eicosanoids. Leukotriene inhibition increased mean arterial pressure, pulmonary and systemic vascular resistance indices, and arterial and mixed venous oxygen saturation and reduced pulmonary hypertension, oxygen delivery, oxygen extraction, oxygen consumption, and all measured mediators. Thromboxane receptor blockade lowered TNF and leukotriene levels, ameliorated systemic and pulmonary vasoconstriction, and significantly increased arterial and tissue oxygenation compared with septic controls. Prostacyclin antagonism reduced prostacyclin plasma concentrations, arterial hypoxemia, and oxygen consumption during sepsis and increased circulating leukotriene B4. CONCLUSIONS: Elevations in plasma TNF predictably precede peak levels of eicosanoids in this model. PAF, leukotrienes, and thromboxane A2 are necessary for pulmonary hypertension during bacteremia. Systemic hypotension and increased vascular permeability are mediated by both leukotrienes and PAF. There are complex interactions among mediators during sepsis and further studies are required to define these relationships.

Haemophilus influenzae in lung explants of patients with end-stage pulmonary disease.

In order to determine the presence and distribution of Haemophilus influenzae in lung tissue sections, we obtained lung explants from 49 lung transplant recipients with cystic fibrosis (CF) (n = 16), chronic obstructive pulmonary disease (COPD) including emphysema (n = 16), bronchiectasis (n = 5), pulmonary hypertension (n = 9), Langerhans cell histiocytosis (n = 1), and idiopathic pulmonary fibrosis (n = 2). Analysis was done by selective culturing, immunoperoxidase (IP) staining, and by polymerase chain reaction (PCR). H. influenzae was cultured from specimens of the lung explants from one CF and one COPD patient. IP staining of tissue sections was positive in 24 patients (10 CF patients, eight COPD patients, two bronchiectasis patients, and four patients with noninfectious pulmonary diseases). IP-positive tissue sections were PCR-positive, and IP-negative sections were PCR-negative. H. influenzae was more frequently detected in tissue sections of lung explants from CF and COPD patients than from patients with bronchiectasis or noninfectious pulmonary diseases. H. influenzae was diffusely present in the epithelium, the submucosa of the bronchi, the bronchioles, the interstitium, and the alveolar epithelium. H. influenzae was localized extracellularly alone and in bacterial clusters, and was also associated with macrophages in CF patients. The results of this study demonstrate that H. influenzae is often present in the lungs of patients with end-stage pulmonary disease, especially CF and COPD patients. H. influenzae is diffusely present in the respiratory epithelium and subepithelial layers of the lungs of these patients.

Effect of amrinone during group B Streptococcus-induced pulmonary hypertension in piglets.

Intravenous infusion of group B Streptococcus (GBS) into neonatal animals produces pulmonary hypertension, ventilation/perfusion (VA/Q) mismatch, and an increase in serum levels of thromboxane B2 (TxB2) and tumor necrosis factor (TNF) alpha. The vasodilator amrinone (amr) is a cGMP-inhibited phosphodiesterase inhibitor and is reported to inhibit thromboxane A2 and TNF production. We hypothesized that infusion of amr would cause pulmonary vasodilation and reduce serum TxB2 and TNF levels in piglets with late phase GBS-induced pulmonary hypertension. The effect of amr on gas exchange was also determined. A continuous infusion of GBS was administered for 5 hr to 4 groups of anesthetized, mechanically ventilated neonatal piglets. An amr bolus of 8 mg/kg was given at 4 hr followed by a 1 hr continuous infusion of either 10 or 20 micrograms/kg/min of amr (amr 10 and amr 20, respectively). Control piglets received a bolus and 1 hr infusion of amr carrier. The infusion of amr, but not of carrier reversed late phase GBS-induced pulmonary hypertension. Piglets infused with amr 20 showed transient selective pulmonary vasodilation, based on a reduced ratio of pulmonary to systemic vascular resistance (PVR/SVR ratio) value at 30 min but not at 1 hr, compared to pre-amr treatment values. The PVR/SVR ratio values for amr 10 and control group did not change after treatment with either amr or carrier. Treatment with amr 10 or 20 did not decrease serum TxB2 or TNF levels or increase VA/Q mismatch.(ABSTRACT TRUNCATED AT 250 WORDS)

Herpesvirus hominis: isolation from human trigeminal ganglion.

Herpesvirus hominis was isolated from the trigeminal ganglion obtained at autopsy from 1 of 22 patients with no clinical evidence of active herpetic disease, and from one patient with malignant lymphoma who died with herpes zoster on the abdomen, pulmonary cytomegalic inclusion disease, and possible oral herpes simplex. Virus was isolated by cocultivation of explants of ganglion with monolayers of Vero green monkey kidney cells and required 3 weeks of culture before viral cytopathic effects were evident. These observations support the concept that latent infection of sensory ganglia may be the source of virus in recurrent herpetic disease in man.