Histopathological Findings Associated With Gastroesophageal Reflux Disease and Aspiration After Lung Transplantation: Initial Brazilian Single-Center Experience.

BACKGROUND: Gastro-esophageal reflux disease (GERD) and broncho-aspiration (BA) are known to increase the risk for chronic lung allograft dysfunction (CLAD). However, specific lung injury mechanisms are not clearly known. The objective of the study was to describe histopathological findings in surveillance lung transbronchial biopsies that can be correlated with episodes of BA in the lung allograft. METHODS: This retrospective analysis of surveillance transbronchial biopsies was performed in lung transplant recipients, with available data of broncho-alveolar fluid (cultures and cytology), lung function parameters, and esophageal functional tests. RESULTS: Were analyzed 11 patients, divided into 3 groups: (1) GERD group: 4 patients with GERD and CLAD diagnosis; (2) control group: 2 patients without GERD or CLAD; and (3) BA group: 5 patients with foreign material in lung biopsies. A histopathological pattern of neutrophilic bronchitis (NB) was present in 4 of 4 cases in the GERD group and in 1 of 5 cases in the BA group in 2 or more biopsy samples; culture samples were all negative; the 5 NB-positive patients developed CLAD and died (3/5) or needed re-transplantation (2/5). The other 3 patients in the BA group had GERD without NB or CLAD. Both patients in the control group had transient NB in biopsies with positive cultures but remained free of CLAD. CONCLUSIONS: Surveillance transbronchial biopsies may provide useful information other than the evaluation of acute cellular rejection and can help to identify high-risk patients for allograft dysfunction related to gastro-esophageal reflux.

Posterior reversible encephalopathy syndrome in lung transplantation: 5 case reports.

Posterior reversible encephalopathy syndrome (PRES) is a cliniconeuroradiologic entity characterized by typical neurologic symptoms with characteristic cerebral image alterations. It has been reported in solid organ transplantations, especially related to the use of calcineurin inhibitors. The incidence of PRES in lung transplantation is unknown and probably under-reported in the literature. Here we describe 5 cases of PRES after bilateral lung transplantation. One of the reported cases was the first in the literature in which the neurologic onset precluded the introduction of calcineurin inhibitor. Therefore, although calcineurin inhibitors are known to play an important role in the development of PRES in the setting of lung transplantation, other causes seems to be involved in the physiopathology of this syndrome.

Fungal infection by Mucorales order in lung transplantation: 4 case reports.

Mucorales is a fungus that causes systemic, highly lethal infections in immunocompromised patients. The overall mortality of pulmonary mucormycosis can reach 95%. This work is a review of medical records of 200 lung transplant recipients between the years of 2003 and 2013, in order to identify the prevalence of Mucorales in the Lung Transplantation service of Heart Institute (InCor), Hospital das Clínicas da Universidade de São Paulo, Brazil, by culture results from bronchoalveolar lavage and necropsy findings. We report 4 cases found at this analyses: 3 in patients with cystic fibrosis and 1 in a patient with bronchiectasis due to Kartagener syndrome. There were 2 unfavorable outcomes related to the presence of Mucorales, 1 by reduction of immunosuppression, another by invasive infection. Another patient died from renal and septic complications from another etiology. One patient was diagnosed at autopsy just 5 days after lung transplantation, with the Mucor inside the pulmonary vein with a precise, well-defined involvement only of donor's segment, leading to previous colonization hypothesis. There are few case reports of Mucorales infection in lung transplantation in the literature. Surveillance for the presence of Mucor can lead to timely fungal treatment and reduce morbidity and mortality in the immunocompromised patients, especially lung transplant recipients.

Risk factors and survival impact of primary graft dysfunction after lung transplantation in a single institution.

BACKGROUND: Lung transplantation has become a standard procedure for some end-stage lung diseases, but primary graft dysfunction (PGD) is an inherent problem that impacts early and late outcomes. The aim of this study was to define the incidence, risk factors, and impact of mechanical ventilation time on mortality rates among a retrospective cohort of lung transplantations performed in a single institution. METHODS: We performed a retrospective study of 118 lung transplantations performed between January 2003 and July 2010. The most severe form of PGD (grade III) as defined at 48 and 72 hours was examined for risk factors by multivariable logistic regression models using donor, recipient, and transplant variables. RESULTS: The overall incidence of PGD at 48 hours was 19.8%, and 15.4% at 72 hours. According multivariate analysis, risk factors associated with PGD were donor smoking history for 48 hours (adjusted odds ratio [OR], 4.83; 95% confidence interval [CI], 1.236-18.896; P = .022) and older donors for 72 hours (adjusted OR, 1.046; 95% CI, 0.997-1.098; P = .022). The operative mortality was 52.9% among patients with PGD versus 20.3% at 48 hours (P = .012). At 72 hours, the mortality rate was 58.3% versus 21.2% (P = .013). The 90-days mortality was also higher among patients with PGD. The mechanical ventilation time was longer in patients with PGD III at 48 hours namely, a mean time of 72 versus 24 hours (P = .001). When PGD was defined at 72 hours, the mean ventilation time was even longer, namely 151 versus 24 hours (P < .001). The mean overall survival for patients who developed PGD at 48 hours was 490.9 versus 1665.5 days for subjects without PGD (P = .001). Considering PGD only at 72 hours, the mean survival was 177.7 days for the PGD group and 1628.9 days for the other patients (P < .001). CONCLUSION: PGD showed an important impacts on operative and 90-day mortality rates, mechanical ventilation time, and overall survival among lung transplant patients. PGD at 72 hours was a better predictor of lung transplant outcomes than at 48 hours. The use of donors with a smoking history or of advanced age were risk factors for the development of PGD.

Impact of cytomegalovirus infection in lung transplant patients under universal prophylaxis: single-center experience in Brazil.

INTRODUCTION: Cytomegalovirus (CMV) infection, a common complication in lung transplant (LT) patients, is associated with worse outcomes. Therefore, prophylaxis and surveillance with preemptive treatment is recommended. OBJECTIVES: Describe the epidemiology and impact on mortality of CMV infection in LT patients receiving CMV prophylaxis. METHODS: Single-center retrospective cohort of LT recipients from August 2003 to March 2008. We excluded patients with survival or follow-up shorter than 30 days. We reviewed medical charts and all CMV pp65 antigen results. RESULTS: Forty-seven patients met the inclusion criteria and 19 (40%) developed a CMV event: eight CMV infections, seven CMV syndromes, and 15 CMV diseases. The mean number of CMV events for each patient was 1.68 +/- 0.88. Twelve patients developed CMV events during prophylaxis (5/12 had CMV serology D+/R-). Forty-six of the 47 patients had at least one episode of acute rejection (mean 2.23 +/- 1.1). Median follow-up was 22 months (range = 3-50). There were seven deaths. Upon univariate analysis, CMV events were related to greater mortality (P = .04), especially if the patient experienced more than two events (P = .013) and if the first event occurred during the first 3 months after LT (P = .003). Nevertheless, a marginally significant relationship between CMV event during the first 3 months after LT and mortality was observed in the multivariate analysis (hazards ratio: 7.46; 95% confidence interval: 0.98-56.63; P = .052). Patients with CMV events more than 3 months post-LT showed the same survival as those who remained CMV-free. CONCLUSION: Prophylaxis and preemptive treatment are safe and effective; however, the patients who develop CMV events during prophylaxis experience a worse prognosis.

Cytokine profile in pleural fluid and serum after lung transplantation.

BACKGROUND: Lung transplantation is the procedure of choice in several end-stage lung diseases. Despite improvements in surgical techniques and immunosuppression, early postoperative complications occur frequently. OBJECTIVE: To evaluate the pleural inflammatory response after surgery. PATIENTS AND METHODS: Twenty patients aged 18 to 63 years underwent unilateral or bilateral lung transplantation between August 2006 and March 2008. Proinflammatory cytokines interleukin (IL)-1beta, IL-6, and IL-8 and vascular endothelial growth factor in pleural fluid and serum were analyzed. For cytokine evaluation, 20-mL samples of pleural fluid and blood (right, left, or both chest cavities) were obtained at 6 hours after surgery and daily until removal of the chest tube or for a maximum of 10 days. Data were analyzed using analysis of variance followed by the Holm-Sidak test. RESULTS: All effusions were exudates according to Light's criteria. Pleural fluid cytokine concentrations were highest at 6 hours after surgery. Serum concentrations were lower than those in pleural fluid, and IL-1beta, IL-6, and IL-8 were undetectable at all time points. CONCLUSIONS: There is a peak concentration of inflammatory cytokines in the first 6 hours after transplantation, probably reflecting the effects of surgical manipulation. The decrease observed from postoperative day 1 and thereafter suggests the action of the immunosuppression agents and a temporal reduction in pleural inflammation.

São Paulo lung transplantation waiting list: patient characteristics and predictors of death.

INTRODUCTION: Nowadays, lung transplantation (LTx) allocation in Brazil is based mainly on waiting time. There is a need to evaluate the equity of the current lung allocation system. OBJECTIVES: We sought to (1) determine the characteristics of registered patients on the waiting list and (2) identify predictors of death on the list. MATERIALS AND METHODS: We analyzed the medical records as well as clinical and laboratory data of 164 patients registered on the waiting list from 2001 to June 2008. Predictors of mortality were obtained using Cox proportional hazards analysis. RESULTS: Patients who were registered on the waiting list showed a mean age of 36.1 +/- 15.0 vs. 42.2 +/- 15.7 years, considering those who did versus did not, die on the list, respectively (P = .054). Emphysema was the most prevalent underlying disease among the patients who did not die on the list (28.8%); its prevalence was low among the patients who died on the list (6.5%; P = .009). The following variables correlated with the probability of death on the waiting list: emphysema or bronchiectasis diagnosis (hazard ratio [HR] = 0.15; P = .002); activated partial thromboplastin time > 30 seconds (HR = 3.28; P = .002); serum albumin > 3.5 g/dL (HR = 0.41; P = .033); and hemoglobin saturation > 85% (HR = 0.44; P = .031). CONCLUSIONS: Some variables seemed to predict death on the LTx waiting list; these characteristics should be used to improve the LTx allocation criteria in Brazil.

Uso do suporte ventilatório com pressäo positiva contínua em vias aéreas (CPAP) por meio de máscara nasofacial no tratamento da insuficiência respiratória aguda / Continuous positive airway pressure (CPAP) by face mask to treat acute respiratory failure

Objetivo. O objetivo dos autores foi avaliar o efeito da ventilaçäo com CPAP oferecida por meio de máscara nasofacial como método de suporte ventilatório em pacientes com insuficiência respiratória aguda com critérios de indicaçäo para intubaçäo traqueal. Casuística e Método. Foram estudados 11 pacientes com idade média de 41,3 anos em insuficiência respiratória aguda internados na Unidade Respiratória do Hospital Säo Paulo - Escola Paulista de Medicina. A admissäo, era colhida gasometria arterial em ar ambiente e monitorizava-se freqüência respiratória (f), freqüência cardíaca (FC) e pressäo arterial (PA). Os mesmos parâmetros eram avaliados após oxigenoterapia via máscara facial aberta e com máscara facial de CPAP usando PEEP de 5cm H2O. Resultados. Com o uso de CPAP através de máscara nasofacial, houve melhora significativa dos níveis de PaO2 e diminuiçäo da freqüência respiratória (<0,05), quando comparados aos valores em ar ambiemte e com máscara facial aberta. Conclusäo. Este trabalho permitiu concluir que a máscara facial de CPAP com 5cm H2O foi eficiente em melhorar a oxigenaçäo arterial e diminuir a freqüência respiratória dos pacientes com insuficiência respiratória aguda, proporcionando-lhes maior conforto, constituindo uma medida terapêutica capaz de evitar o suporte ventilatório invasivo.

[Continuous positive airway pressure (CPAP) with face mask to treat acute respiratory failure]. / Uso do suporte ventilatório com pressão positiva contínua em vias aéreas (CPAP) por meio de máscara nasofacial no tratamento da insuficiência respiratória aguda.

OBJECTIVE: To evaluate the efficacy of continuous positive airway pressure (CPAP) administered by face mask in patients with acute respiratory failure with indication of mechanical ventilation. MATERIALS AND METHOD: Eleven patients (mean age 41.3 years) in acute respiratory failure were admitted in the Respiratory Unit--Hospital São Paulo--Escola Paulista de Medicina. At the admission pH, PaO2, PaCO2, respiratory rate (f), arterial pressure and heart rate were measured. The measurements were repeated with administration of oxygen with a high flow face mask at ambient airway pressure and then with 5 cm H2O of CPAP by face mask. RESULTS: The use of CPAP by face mask significantly improved the arterial blood oxygenation and decreased the respiratory rate (p < 0.05). CONCLUSION: These data allow the conclusion that CPAP administered by face mask improves gas exchange and decreases respiratory rate in patients with acute respiratory failure and may reduce the need for invasive mechanical ventilation.

[Effect of dopamine in dopaminergic doses on pulmonary circulation of dogs in normoxia and hypoxia]. / Efeitos da dopamina em doses dopaminérgicas sobre a circulação pulmonar de cães em normóxia e hipóxia.

PURPOSE: To study if dopamine in dopaminergic doses (1.5 and 4.0 micrograms/kg/min) had some effect on the pulmonary vasoconstriction mechanism, and if in those doses the drug had some action on systemic and pulmonary hemodynamic variables, as well as in the pulmonary gas exchange. METHODS: Seventeen normal mongrel dogs, anesthetized and paralized under mechanical ventilation were submitted to two different gas mixtures: room air (F1O2 = 0.2093 -10 dogs) and hypoxic mixture (F1O2 = 0.125 -7 dogs). Dopamine was infused in both groups during 15 min in the two doses 1.5 and 4.0 micrograms/km/min, separated by a period of 30 min. RESULTS: Pulmonary hemodynamics and gas exchange variables after infusion of dopamine at 1.5 and 4.0 micrograms/km/min in dogs in normoxia and hypoxia. [table: see text] CONCLUSION: Dopamine in the used doses had no action on the pulmonary circulation and on the hypoxic pulmonary vasoconstriction mechanism; pulmonary gas exchange was not affected by dopamine in both doses during normoxia and hypoxia; in the experimental model there was no evidence of dopaminergic receptors in the pulmonary vessels.

Gas exchange during differential mechanical ventilation after unilateral lung injury induced by hydrochloric acid: experimental study in dogs

In order to test gas exchange in lungs with unilateral injury, when mechanical ventilation is needed, three groups (G-I, G-II, G-III) of seven dogs each were studied. Injury was induced in the left lung by injecting 0,lN, 1.0 ml per kg of body weight of hydrochloric acid, pH = 2.00. For groups I and II a conventional volumetric artificial ventilator was used. G-I was the control group. In group II a bilateral positive end-expiratory pressure (PEEP) was introduced during the last phase (phase 3) of the experiment, and in group III, a prototype of a volume cycled ventilator, with separated bellows, was used delivering tidal volumes separately to each lung through a Carlens' tube. In G-III, PEEP was introduced only to the injured lung in the last phase of the experiment. Phase l (Fl), basal phase, was similar in the three groups; phase 2 (F2) was the period after instillation of hydrochloric acid and phase 3 was the period after a 5 cmH2O bilateral PEEP was used in G-II, and a selective PEEP to the left lung was used in G-III. In each phase of the experiment, hemodynamic and gas exchange variables were obtained. Our results allowed the following conclusions: the differential lung ventilation technique maintained the alveolar ventilation of the dogs and the differential lung ventilation with unilateral PEEP was better for gas exchange (phase 3) than the conventional ventilation with bilateral PEEP (CPPB).

Hemodinâmica e pressöes de vias aéreas na ventilaçäo em paralelo dos pulmöes após lesäo unilateral com ácido clorídrico: estudo experimental em cäes / Hemodynamics and airway pressures in parallel lung ventilation after unilateral injury with hydrochloric acid: experimental study in dogs

Os autores estudam as repercussöes sobre pressöes de vias aéreas e hemodinâmica pulmonar e sistêmica da ventilaçäo pulmonar em paralelo comparando-as com a ventilaçäo pulmonar clássica em modelo experimental em que foi produzida lesäo nos pulmöes esquerdos por instilaçäo endotraqueal de ácido clorídrico 0,1 N, pH = 2,00, 1 ml/kg de peso corpóreo, em cäes. Três grupos de sete cäes cada foram estudados: Grupo I (GI) - com ventilador a volume clássico, grupo controle, em que, após a fase basal (FI), foi produzida lesäo (F2) e näo foi instalada pressäo positiva expiratória (PPE) (F3); Grupo II (GII) - idêntico ao grupo GI, mas em F3 foi instalada PPE de 5 cmH2O bilateralmente; e Grupo III (GIII) - ventilado com ventilador volumétrico (protótipo Takaoka) para ventilaçäo em separado dos pulmöes, utilizando-se na F3 PPE unilateral exclusivamente nos pulmöes lesados. Os resultados mostraram que a ventilaçäo pulmonar em paralelo mostrou-se: 1. técnica eficiente para manter a ventilaçäo alveolar dos cäes; 2. protegeu o pulmäo sadio de aumentos nas pressöes de vias aéreas provocados após a lesäo pulmonar, enquanto durante a ventilaçäo convencional houve grande aumento nas pressöes de vias aéreas, bilateralmente. Quanto às repercussöes hemodinâmicas, näo foram observadas diferenças entre os três grupos de cäes

Ateracoes estruturais pulmonares secundarias ao trombembolismo. Estudo experimental em caes. / Pulmonary structural changes secondary to thromboembolism. Experimental study in dogs

Foram estudadas, em caes, as modificacoes estruturais pulmonares secundarias a injecao de coagulos autologos produzidos in vitro. O estudo anatomopatologico dos pulmoes, fixados em expansao, foi precedido por arteriografia post-mortem. Os autores salientam a utilidade desta metodologia e descrevem as alteracoes radiologicas, macro e microscopicas, encontradas

Fisiopatologia da asma bronquica. / Physiopathology of bronchial asthma

Ainda nao existe consenso sobre a definicao de asma. Adotamos a definicao da Sociedade Toracica Americana.Dentre as classificacoes propostas da doenca, destacamos as caracteristicas diferenciais entre asma extrinseca (ou alergica) e asma intrinseca Sendo a asma uma doenca na qual a resistencia das vias aereas aumenta em resposta a varios estimulos, quer alergenicos ou nao, diversas teorias tentam explicar a sua fisiopatologia. As causas de broncoconstricao mais comuns sao alergenos, infeccoes virais, ar frio, exercicio e poluentes aereos. Assim, quando ha sensibilizacao antigenica, moleculas de IgE ligadas a receptores dos mastocitos desencadeiam a producao e liberacao de mediadores quimicos (histamina, SRS-A, PAF e prostaglandinas, etc.). Estes por via direta e por via reflexa levam a broncoconstricao e hipersecrecao mucosa. Porem a hiper-reatividade bronquica, caracteristica de todos os tipos de asma poderia depender de um bloqueio parcial ou completo dos receptores beta, com predominio dos receptores alfa e consequente broncoconstricao. Pode ocorrer tambem irritacao de fibras do parassimpatico na parede bronquica

Deteccao da asma induzida pelo exercicio por testes espirometricos. / Diagnosis of exercise induced asthma by spirometric tests

Os autores analisam a sensibilidade de 4 testes simples (PFE, CVF, VEF1 e FEF 25 - 75%) para a deteccao de asma induzida por exercicio. Com este objetivo estudaram 40 pacientes asmaticos submetidos a teste de esforco; 12 eram do sexo masculino (30%) e 28 do sexo feminino (70%) com idade media de 18,7 +/- 5,7 anos.Os testes foram analisados antes e 5, 10 e 20 minutos apos o exercicio. Considerou-se com tendo asma induzida por exercicio aquele paciente que alterasse no minimo 20% em pelo menos um teste dentre os quatro. Considerou-se a soma dos resultados de cada parametro isolado, 19 pacientes desenvolveram broncoespasmo apos o exercicio. O FEF25 - 75% detectou 15 pacientes, o VEF1 14, o PFE 8 e a CVF 6. A maior dimunuicao, (5 min. = 41,7%, 10 min. = 44,1% e 20 min. = 39,3%). Se considerarmos que 20 min igual 39,3%). Se considerarmos que pelo menos dois testes deveriam estar alterados, quatro pacientes ficam excluidos do diagnostico inicial. Com isso ficam excluidos pacientes que podem nao ter colaborado naqueles testes que dependem principalmente da cooperacao do individuoCVF e PFE. O uso concomitante do VEF1 e FEF25-75% torna mais rigoroso o criterio diagnostico

Drogas beta-2 adrenergicas por via parenteral na crise aguda de asma. / Beta-2 adrenergic drugs by parenteral route in acute attack of asthma

Os efeitos broncodilatadores de tres drogas beta-2 adrenergicas - salbutamol (S) (500 microgramo por via subcutanea), terbutalina (T) (500 microgramo por via subcutanea) e fenoterol (F) (500 microgramo por via intravenosa) - foram testados aleatoriamente em tres grupos de seis pacientes com crise aguda de asma bronquica.Foram analisados CVF, FEF 25-75% e PF em cada paciente antes e 15,30, 45,60, 120 e 180 minutos apos as drogas. Comparando-se os valores medios pre, 30 minutos pos-droga, os pacientes do grupo S apresentaram incrementos de CVF = 30,8%, VEF1 = 40,0%, FEF 25-75% = 212,2 e PFE = 49,8%. Os pacientes do grupo T tiveram incrementos de CVF = 24,2%, VEF1 = 46,6%, FEF 25-75% = 248,7% e PFE = 112,7% As tres drogas foram broncodilatadores eficientes nao se demonstrando diferenca estatisticamente significante entre elas

Acao de pressao positiva expiratoria (PPE) no edema pulmonar por aumento da permeabilidade microvascular. / The effect of positive end expiratory pressure on lung edema due to increased microvascular permeability

Com o objetivo de analisar o papel da pressao positiva expiratoria (PPE) sobre o edema pulmonar por aumento de permeabilidade microvascular foram estudados 18 caes divididos em tres grupos. No grupo I, os caes eram ventilados com respirador a volume a apos 30 minutos instalavamos PPE de 5 cmH2O. No grupo II, os caes eram ventilados com respirador a volume e provocava-se edema pulmonar por injecao endovenosa de aloxana de 90 mg/kg, e, no grupo III, procediamos como no grupo II e apos 30 minutos instalavamos 5 cmH2O de PPE.Apos 120 minutos os pulmoes foram retirados.Para avaliarmos o edema ocorrido utilizamos o pulmao esquerdo para calcularmos a relacao peso unico/peso seco (PU/PS) foi, no grupo I 4,01 +/- 0,69, grupo II 8,78 +/- 2,29, e no grupo III 8,18 +/- 2,33: os grupos II e III apresentaram aumento significante desta relacao quando comparado ao grupo I. A microscopia revelou ausencia de edema no grupo I e intenso edema em iguais proporcoes nos grupos II e III. Pudemos concluir que: a aplicacao de 5 cmH2O de PPE nao provocou edema pulmonar: e que a quantificacao do edema pulmonar decorrente de aumento de permeabilidade microvascular nao se modificou com a utilizacao de ventilacao com PPE de 5 cmH2O