RESUMEN
Chronic thromboembolic pulmonary hypertension (CTEPH) involves abnormally high blood pressure in the pulmonary vessels and is associated with small vessel vasculopathy and pre-capillary proximal occlusions. Management of CTEPH disease is challenging, therefore accurate diagnosis is crucial in ensuring effective treatment and improved patient outcomes. The treatment of choice for CTEPH is pulmonary endarterectomy, which is an invasive surgical intervention to remove thrombi. Following PEA, a number of patients experience poor outcomes or worse-than-expected improvements, which may indicate that they have significant small vessel disease. A method that can predict the extent of distal remodelling may provide useful clinical information to plan appropriate CTEPH patient treatment. Here, a novel biophysical modelling approach has been developed to estimate and quantify the extent of distal remodelling. This method includes a combination of mathematical modelling and computed tomography pulmonary angiography to first model the geometry of the pulmonary arteries and to identify the under-perfused regions in CTEPH. The geometric model is then used alongside haemodynamic measurements from right heart catheterisation to predict distal remodelling. In this study, the method is tested and validated using synthetically generated remodelling data. Then, a preliminary application of this technique to patient data is shown to demonstrate the potential of the approach for use in the clinical setting.Clinical relevance- Patient-specific modelling can help provide useful information regarding the extent of distal vasculopathy on a per-patient basis, which remains challenging. Physicians can be unsure of outcomes following pulmonary endarterectomy. Therefore, the predictive aspect of the patient's response to surgery can help with clinical decision-making.
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Hipertensión Pulmonar , Hipertensión , Embolia Pulmonar , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/cirugía , Embolia Pulmonar/complicaciones , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/cirugía , Arteria Pulmonar/cirugía , PulmónRESUMEN
BACKGROUND: Multivitamins are a popular supplement taken to promote physical and mental health. During periods of stress, they may have a protective role for health and wellbeing, although the current evidence of their efficacy is mixed. OBJECTIVE: To determine whether multivitamin supplementation impacts psychological and inflammatory markers of women who are experiencing psychological distress. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: An 8-week randomized controlled trial was conducted to assess changes in both psychological state and pro-inflammatory markers of patients receiving multivitamins or placebo. The sample comprised women who reported elevated psychological distress in the previous 4â¯weeks. MAIN OUTCOME MEASURES: Psychological state was assessed using Spielberger's State-Trait Personality Inventory to assess anxiety, curiosity, depression and anger. Pro-inflammatory markers comprised interleukin (IL)-1ß, IL-5, IL-6, tumour necrosis factor (TNF)-α and TNF-ß. RESULTS: Improvements across time were observed for all psychological measures and cytokines, except IL-5, but were independent of the active intervention. Only TNF-ß demonstrated a significant differential change between groups over the course of the intervention, in favour of multivitamin supplementation (active group mean rank decreased from 11.1 to 7.1; placebo group mean rank decreased from 8.9 to 7.8). CONCLUSION: The results suggest that administration of multivitamins was not effective in improving psychological state. However, some evidence supported the positive impact of multivitamin supplementation on pro-inflammatory cytokine profiles of women currently experiencing stress.
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Citocinas/sangre , Suplementos Dietéticos , Inflamación/sangre , Estrés Psicológico/sangre , Vitaminas/uso terapéutico , Adulto , Ira , Ansiedad/sangre , Ansiedad/tratamiento farmacológico , Depresión/sangre , Depresión/tratamiento farmacológico , Método Doble Ciego , Conducta Exploratoria , Femenino , Humanos , Inflamación/complicaciones , Inflamación/psicología , Estrés Psicológico/tratamiento farmacológicoRESUMEN
We present management strategies utilised for the first case of an urgent live-donor ABO incompatible B blood group renal transplant, in a patient with a prior A blood group lung transplant for cystic fibrosis. Three years on, renal function is excellent and stable, whilst lung function has improved.
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Sistema del Grupo Sanguíneo ABO/inmunología , Fibrosis Quística/terapia , Rechazo de Injerto/inmunología , Isoantígenos/inmunología , Fallo Renal Crónico/terapia , Trasplante de Riñón , Trasplante de Pulmón , Sepsis/terapia , Enfermedad Aguda , Adulto , Supervivencia sin Enfermedad , Femenino , Rechazo de Injerto/tratamiento farmacológico , Antígenos HLA/inmunología , Humanos , Donadores Vivos , Persona de Mediana Edad , Madres , Ácido Micofenólico/uso terapéutico , Plasmaféresis , Prednisolona/uso terapéutico , Tacrolimus/uso terapéutico , Privación de TratamientoRESUMEN
Lung transplantation (LTx) is a therapeutic option for severe pulmonary arterial hypertension (PAH) patients failing optimal medical therapy. The use of donation after circulatory determination of death (DCDD) donor lungs for PAH LTx has rarely been reported, primarily reflecting concerns that DCDD lungs represent extended criteria donors, at risk of morbidity and mortality. A retrospective study of all Alfred Hospital DCDD and DNDD (donation after neurologic determination of death) PAH LTx was undertaken. Protocolized fluid/inotrope/ventilator and extracorporeal membrane oxygenation (ECMO) strategies were utilized. Since our first DCDD LTx in 2006, 512 LTx have been performed. Of 31 PAH recipients, 11 received DCDD lungs (11% of DCDD LTx) and 20 received DNDD lungs (5% of DNDD LTx) (p = 0.04). Only one PAH patient died on the LTx waiting list. Peri-LTx ECMO was utilized in 3/11 (27%) DCDD and 6/20 (30%) DNDD PAH LTx (p = 0.68). Primary graft dysfunction, intensive care, and overall stay were the same in both groups. Survival at 1 and 8 years was 100% and 80% for DCDD versus 100% and 70% for DNDD LTx (p = 0.88), respectively. In conclusion, excellent results can be achieved for PAH LTx. DCDD donor lungs are not extended lungs per se having passed the toughest test.
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Circulación Sanguínea , Muerte Encefálica , Rechazo de Injerto/epidemiología , Hipertensión Pulmonar/cirugía , Trasplante de Pulmón , Arteria Pulmonar/cirugía , Donantes de Tejidos , Adolescente , Adulto , Australia/epidemiología , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Disfunción Primaria del Injerto , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Obtención de Tejidos y Órganos , Adulto JovenRESUMEN
BACKGROUND: The management of children with congenital heart disease (CHD) has improved over recent decades and several patients surviving with CHD into adulthood are increasing. In developed countries, there are now as many adults as there are children living with CHD. Pulmonary arterial hypertension (PAH) occurs in â¼ 5% of patients with CHD. AIM: We aimed to understand the characteristics and outcomes of this emerging population. METHODS: We collected data retrospectively and prospectively from 12 contributing centres across Australia and New Zealand (2010-2013). Patients were included if they had been diagnosed with PAH and CHD and had been seen once in an adult centre after 1 January 2000. RESULTS: Of 360 patients with CHD-PAH, 60% were female and 90% were New York Heart Association functional class II or III at the time of adult diagnosis of PAH. Mean age at diagnosis of PAH in adulthood was 31.2 ± 14 years, and on average, patients were diagnosed with PAH 6 years after symptom onset. All-cause mortality was 12% at 5 years, 21% at 10 years and 31% at 15 years. One hundred and six patients (30%) experienced 247 hospitalisations during 2936 patient years of follow up. Eighty-nine per cent of patients were prescribed PAH specific therapy (mean exposure of 4.0 years). CONCLUSIONS: Adults with PAH and CHD often have this diagnosis made after significant delay, and have substantial medium-term morbidity and mortality. This suggests a need for children transitioning to adult care with CHD to be closely monitored for this complication.
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Antihipertensivos/administración & dosificación , Antagonistas de los Receptores de Endotelina/administración & dosificación , Cardiopatías Congénitas/epidemiología , Hipertensión Pulmonar/epidemiología , Sistema de Registros , Adulto , Australia/epidemiología , Terapia Combinada , Diuréticos , Femenino , Estudios de Seguimiento , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/fisiopatología , Humanos , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/fisiopatología , Masculino , Nueva Zelanda/epidemiología , Calidad de Vida , Estudios Retrospectivos , Factores de RiesgoRESUMEN
This is the first prospective study in a contemporary Australian/New Zealand population to determine the prevalence of testosterone deficiency in testicular cancer survivors at 12 months from treatment, and any association with poorer quality of life. Hormone assays from 54 evaluable patients in a prospective cohort study revealed biochemical hypogonadism in 18 patients (33%) and low-normal testosterone in 13 patients (24%). We found no association between testosterone levels and quality of life (all P > 0.05). Hypogonadal patients should be considered for testosterone replacement to prevent long-term morbidity.
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Terapia de Reemplazo de Hormonas/métodos , Neoplasias de Células Germinales y Embrionarias/sangre , Calidad de Vida , Neoplasias Testiculares/sangre , Testosterona/deficiencia , Adulto , Australia/epidemiología , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/epidemiología , Nueva Zelanda/epidemiología , Prevalencia , Estudios Prospectivos , Tasa de Supervivencia/tendencias , Sobrevivientes , Neoplasias Testiculares/tratamiento farmacológico , Neoplasias Testiculares/epidemiología , Adulto JovenRESUMEN
BACKGROUND: IVI epoprostenol is the only therapy for pulmonary arterial hypertension (PAH) with a randomized controlled trial demonstrating improved survival, when used as first-line monotherapy. In Australia it is used as salvage therapy for those failing treatment with other targeted therapies or presenting in World Health Organization functional class (FC) IV. AIMS: Report experience with IVI epoprostenol, administered as salvage therapy for the treatment of adults with PAH in a single Australian PAH centre. METHODS: Retrospective case series of all patients commenced on IVI epoprostenol for PAH, between 2002 and 2010. Review of case notes with collection of data at baseline and after treatment, including FC, 6-min walk test (6MWT), right ventricular systolic pressure (RVSP) on echocardiogram, patient survival and treatment complications. Change in indices was assessed using the Wilcoxon Sign Rank Test and is expressed as median (inter-quartile range). RESULTS: A total of 23 patients was included. Treatment was generally well tolerated with few major complications. At the end of the study period, nine patients were successfully bridged to transplant, five had a sustained response to IVI epoprostenol, six had an incomplete response but were clinically stabilized, two died awaiting transplant and one died who was not a candidate for transplantation. Overall, when measured at best level post initiation of IVI epoprostenol, there were significant improvements in FC -1 [0 to -1] (P < 0.0001), 6MWT (m) +117 [70-264] (P= 0.002) and RVSP (mmHg) -7.0 [4.0 to -45] (P= 0.03). CONCLUSION: Findings support efficacy of epoprostenol as salvage therapy for patients with PAH.
Asunto(s)
Epoprostenol/administración & dosificación , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/epidemiología , Terapia Recuperativa , Adulto , Anciano , Australia/epidemiología , Niño , Hipertensión Pulmonar Primaria Familiar , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Terapia Recuperativa/métodos , Adulto JovenRESUMEN
Interstitial lung disease (ILD) has been reported to have a poor outcome following lung transplantation due to difficulties getting ill recipients to transplantation and challenging early postoperative outcomes. To assess long-term outcomes for this cohort, we performed a retrospective 18-year chart review of all ILD lung transplant recipients. ILD single (SLT) and bilateral sequential lung transplantations (BSLT) were compared with all other lung transplant patients and International Society for Heart and Lung Transplantation (ISHLT) Registry data over the same time period. Of 585 lung transplantations, 90 (15%) were ILD (53 SLT, 37 BSLT); 67 (74%) were idiopathic pulmonary fibrosis (IPF), 9 (10%) were sarcoidosis, 9 (10%) were lymphangioleiomyomatosis, and 5 (6%) had other indications. Mean age was 52 years (range, 34-69 years). Actuarial survival at 1, 5, 10, 15, and 18 years compared favorably to all other lung transplantations performed (77% vs 83%, 51% vs 50%, 42% vs 26%, 28% vs 17%, and 28% vs 8%, respectively). IPF actuarial survival at 1, 5, and 10 years appeared superior to ISHLT Registry data (76% vs 72%, 50% vs 44%, and 34% vs 20%, respectively). There was equivocal survival between SLT and BSLT at 1, 5, and 10 years (78% vs 68%, 49% vs 50%, and 29% vs 50%, respectively). Our ILD figures compared favorably to lung transplantation for other diseases and international standards, while survival from SLT was as successful as BSLT both in the short and the longer term. Consideration should be given to utilizing SLT to maximize the allocation of donor lungs and to decrease waiting list mortality associated with IPF.
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Trasplante de Pulmón/fisiología , Fibrosis Pulmonar/cirugía , Estudios de Cohortes , Estudios de Seguimiento , Humanos , Soluciones Hipertónicas , Trasplante de Pulmón/mortalidad , Preservación de Órganos/métodos , Soluciones Preservantes de Órganos , Estudios Retrospectivos , Análisis de Supervivencia , Sobrevivientes , Factores de Tiempo , Resultado del TratamientoRESUMEN
UNLABELLED: Bronchoalveolar lavage (BAL) neutrophilia has been repeatedly observed in lung transplant recipients with established bronchiolitis obliterans syndrome (BOS). Little is known of the fluctuations in BAL and airway neutrophilic inflammation post-transplant. This prospective longitudinal study aimed to evaluate the dynamic changes of lung allograft neutrophils with time, immunosuppression, infection and BOS. A total of 28, initially healthy, BOS 0, lung transplant recipients underwent 134 bronchoscopic assessments, including BAL and endobronchial biopsies (EBB) (with immunohistochemistry) over 3-year follow up. Subsequently, 21 developed BOS 0p and 16 ultimately BOS. Compared to controls, there was early and persistent BAL neutrophilia (p < 0.05), contrasting with an initially normal EBB that shows a progressive increased airway wall neutrophil infiltrate. BAL neutrophilia (but not airway wall neutrophilia) was most striking when there was concomitant bronchopulmonary infection, particularly in the patients with BOS. Univariate and multivariate analyses suggested that BAL neutrophilia was linked to markers of infection while EBB neutrophilia was linked with coexistent inflammation with macrophages and lymphocytes. IN CONCLUSION: (i) BAL neutrophilia is predominantly associated with infection; (ii) Airway wall neutrophilia (as monitored by EBB) increases with time post-transplant and is not associated with infection; (iii) By itself, BOS is not the major contributor to BAL and EBB neutrophilia.
Asunto(s)
Trasplante de Pulmón/patología , Pulmón/patología , Neutrófilos/patología , Adulto , Biopsia , Líquido del Lavado Bronquioalveolar/citología , Broncoscopía , Femenino , Estudios de Seguimiento , Humanos , Trasplante de Pulmón/efectos adversos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Pronóstico , Estudios ProspectivosRESUMEN
BACKGROUND: Inhaled fluticasone propionate (FP) therapy decreases inflammation and sub-basement membrane thickness in asthmatic airways. Bronchiolitis obliterans syndrome (BOS) in lung transplant recipients (LTRs) involves progressive airway fibrosis and obliteration. Therefore, augmented immunosuppression may be of some benefit in treating BOS. In this study, we examined the effect of 3 months of treatment with high-dose inhaled FP on the concentrations of 2 fibrogenic factors, transforming growth factor (TGF)-beta(1) and beta fibrogenic growth factor (bFGF) in bronchoalveolar lavage (BAL) fluid from clinically stable LTRs. METHODS: We conducted a randomized, double-blind, placebo-controlled, parallel group study with inhaled FP (750 microg, twice/day for 3 months) in 28 LTRs (15 FP and 13 placebo). We recruited 23 healthy controls. We performed spirometry, bronchoscopy, and bronchoalveolar lavage procedures before treatment and after 3 months of treatment. We used commercially available enzyme-linked immunosorbent assay kits to measure BAL fluid TGF-beta(1) and bFGF concentrations. RESULTS: In LTRs before treatment, BAL TGF-beta(1) concentrations (but not bFGF concentrations), total cell counts, and neutrophil percentage increased compared with controls (p < 0.05). We found no significant differences between FP and placebo groups at baseline measurements. After treatment, BAL TGF-beta(1) concentrations significantly increased in the FP group (p = 0.03), but we found no difference between FP and placebo groups; BAL bFGF concentrations increased during treatment in both groups compared with controls (p < 0.05), but not significantly within either patient group (p > 0.05). We found a reverse correlation between forced expiratory volume in 1 second (FEV(1)) and BAL TGF-beta(1) concentration in the FP group (r = -0.53, p = 0.04), and between FEV(1) and BAL TGF-beta(1) concentration in the placebo group (r = -0.74, p = 0.004). Multivariable analysis indicated no significant independent effects of inhaled FP in either BAL TGF-beta(1) or bFGF concentrations. CONCLUSIONS: Bronchoalveolar fluid TGF-beta(1) concentrations increased in LTRs after transplantation and may correlate with the decrease in lung function. Inhaled FP added to conventional immunosuppression had no effect on TGF-beta(1) or bFGF production in BAL fluid.
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Androstadienos/administración & dosificación , Antiinflamatorios/administración & dosificación , Líquido del Lavado Bronquioalveolar/química , Factores de Crecimiento de Fibroblastos/efectos de los fármacos , Trasplante de Pulmón/fisiología , Factor de Crecimiento Transformador beta/efectos de los fármacos , Administración por Inhalación , Adulto , Bronquiolitis Obliterante/prevención & control , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Factores de Crecimiento de Fibroblastos/metabolismo , Fluticasona , Humanos , Terapia de Inmunosupresión/métodos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Masculino , Persona de Mediana Edad , Pruebas de Función Respiratoria , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta1RESUMEN
Macrophages, neutrophils and infection have been implicated in the genesis of the bronchiolitis obliterans syndrome (BOS) post lung transplantation. sCD14 is a soluble form of a shed-cell surface protein. It is capable of promoting cytokine-induced inflammation and it's presence in clinically stable lung transplant recipients (LTR) might be important as an early marker of BOS. Bronchalveolar lavage (BAL) and blood samples were taken from 26 stable LTR, at or near their best forced expiratory volume in one second who were free from infection. sCD14 levels were measured via enzyme-linked immunosorbent assay. Cell counts were performed on unfiltered BAL. LTR neutrophil count, BAL sCD14 and serum sCD14 levels were higher than controls (median 3.8% versus 1.3%, p<0.05; 11.5 ng x mL(-1) versus 6 ng x mL(-1), p<0.001; 6.2 microg x mL(-1) versus 2.4 microg x mL(-1), p<0.05, respectively). BAL albumin and sCD14 correlated (regression coefficient: 0.77, p<0.001). In this hypothesis-generating, cross-sectional study, the authors have described for the first time soluble CD14 levels in the bronchoalveolar lavage and serum of stable lung transplant recipients, and show that these are elevated compared to controls. This is a practicable candidate marker system, which can be tested for a predictive role in bronchiolitis obliterans syndrome following lung transplantation. The origin of this cellular protein and its temporal relationship to the development of the bronchiolitis obliterans syndrome remains to be elucidated in more definitive longitudinal studies, which should include other measurements potentially relevant to the innate immune system, such as bronchoalveolar lavage endotoxin levels.
Asunto(s)
Líquido del Lavado Bronquioalveolar/inmunología , Receptores de Lipopolisacáridos/análisis , Trasplante de Pulmón , Inmunología del Trasplante/fisiología , Adulto , Biomarcadores/análisis , Líquido del Lavado Bronquioalveolar/citología , Estudios de Casos y Controles , Estudios Transversales , Femenino , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Probabilidad , Valores de Referencia , Sensibilidad y Especificidad , Solubilidad , Estadísticas no ParamétricasRESUMEN
Recent publications have demonstrated potentially pathologic changes in bronchoalveolar lavage (BAL) from clinically stable lung transplant recipients (SLTRs), but there are few available data on alveolar macrophages (AMs). We formulated the hypothesis that changes in BAL AM and lymphocyte phenotypes would be apparent even in SLTRs.A cross-sectional study using a standardized 3 x 60 ml BAL, investigating lymphocyte and AM phenotypes in 19 SLTRs, 5 subjects with bronchiolitis obliterans syndrome (BOS) and 18 normal control volunteers. BAL lymphocyte and AM markers were assessed using flow cytometry. We confirmed a significant elevation of neutrophils in all lung transplant recipients with a more marked elevation in the BOS subjects. Flow-cytometric analysis showed increased numbers of natural killer (NK; CD56/CD16-positive) cells, increased CD11b- and CD11c-positive CD3 lymphocytes, increased CD8-positive lymphocytes and increased HLA-DR expression in CD8 cells from the lung transplant recipients, when compared with normals (p <.005). In contrast, the expression of a number of AM surface markers, associated with a range of host defense functions against bacteria, fungi and viruses (CD11a, CD11b, CD11c, HLA-DR, CD14), was lower in both SLTRs and those with BOS (p <.05). These novel findings are consistent with complex lymphocyte and macrophage changes that may result from clinically silent infection, partially suppressed rejection, or both.
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Líquido del Lavado Bronquioalveolar , Rechazo de Injerto/inmunología , Trasplante de Pulmón/inmunología , Linfocitos , Macrófagos , Adulto , Anciano , Antígenos CD/sangre , Biomarcadores/sangre , Estudios Transversales , Femenino , Citometría de Flujo , Humanos , Células Asesinas Naturales/inmunología , Linfocitos/inmunología , Macrófagos/inmunología , Masculino , Persona de Mediana Edad , FenotipoAsunto(s)
Trasplante de Corazón/inmunología , Inmunosupresores/uso terapéutico , Trasplante de Pulmón/inmunología , Terapia Recuperativa , Sirolimus/uso terapéutico , Estudios de Seguimiento , Humanos , Inmunosupresores/efectos adversos , Persona de Mediana Edad , Sirolimus/efectos adversos , Resultado del TratamientoRESUMEN
In conditions characterized by airway inflammation, exhaled nitric oxide (eNO) levels are increased. Post-lung transplant bronchiolitis obliterans syndrome (BOS) is characterized by airway inflammation and development of progressive airway narrowing and fibrosis. We have previously shown that in stable lung transplant recipients (LTR), mean eNO levels were not elevated but were still related to the degree of airway neutrophilia within the group. The hypothesis now tested is that in BOS, eNO levels are increased in association with even greater airway neutrophilia and enhanced expression of inducible (iNOS) nitric oxide synthase in the bronchial epithelium. We determined eNO levels in 40 LTR in four groups: well and "stable": LTR (n = 20), BOS (n = 8), bacterial airway infection (BI, n = 6), and acute rejection (AR, n = 6). Following bronchoscopic sampling, we performed a quantitative assessment of iNOS and constitutive nitric oxide synthase (cNOS) expression in endobronchial biopsies by immunohistochemistry. Mean +/- SEM eNO levels in BOS and BI were significantly higher than in stable LTR (20 +/- 1.2 parts per billion [ppb] and 24.7 +/- 1.7 ppb versus 12.5 +/- 0.9 ppb; p < 0.01 for both). In AR, eNO levels (13.4 ppb +/- 0.5) were not different in stable LTR (p = 0.34). When compared with stable LTR, there was increased expression of iNOS in the bronchial epithelium and generally in the lamina propria (LP) in patients with BOS and BI. In AR, iNOS expression was increased but only in the LP in a perivascular distribution. Expression of cNOS was reduced in BOS but not in BI and AR compared with the stable group. Using regression analysis, only iNOS expression in the bronchial epithelium (r(2) = 0.77; p < 0.0001) and %BAL neutrophils (r(2) = 0. 79; p < 0.0001) were positively related to eNO in stable LTR and BOS. We conclude that epithelial iNOS appears to be the major source of eNO. Exhaled NO levels also appear to reflect the degree of airway neutrophilia in both stable LTR and BOS groups. This suggests that serial eNO measurements may be able to predict the early development of BOS.
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Bronquios/enzimología , Neumonía en Organización Criptogénica/metabolismo , Trasplante de Pulmón/efectos adversos , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico/metabolismo , Complicaciones Posoperatorias/metabolismo , Enfermedad Aguda , Análisis de Varianza , Pruebas Respiratorias , Broncoscopía , Epitelio/enzimología , Femenino , Rechazo de Injerto/metabolismo , Humanos , Inmunohistoquímica , Trasplante de Pulmón/fisiología , Masculino , Óxido Nítrico Sintasa de Tipo II , Estadísticas no ParamétricasRESUMEN
UNLABELLED: Bronchiolitis Obliterans Syndrome (BOS) remains a major cause of long term morbidity and mortality in lung transplantation, and occurs despite significant immunosuppression. Airway inflammation is thought to precede the development of BOS. OBJECTIVES: To examine the effect of inhaled corticosteroids on airway inflammation and the development of BOS in lung transplant recipients. METHODS: 30 patients were recruited and randomised in a double blind fashion to receive either 750 micrograms Fluticasone propionate (FP) twice daily or an identical appearing placebo for 3 months. BAL cell counts and differentials were performed at time 0 and after 3 months treatment. Lung function was assessed at each time point using spirometry. RESULTS: 24 patients were felt to be stable and free from infection at both time points and thus included in the analysis. There was a significant reduction in total cell count in BAL fluid after treatment with 3 months FP compared to 3 months placebo, however no change in cell differentials nor lung function was found. DISCUSSION: Despite a reduction in total cell numbers in BAL fluid, lung function was not altered over the 3 months of treatment. It may be that longer treatment is required to see an effect.
Asunto(s)
Corticoesteroides/administración & dosificación , Líquido del Lavado Bronquioalveolar/citología , Inmunosupresores/administración & dosificación , Trasplante de Pulmón/patología , Administración por Inhalación , Adulto , Bronquiolitis Obliterante/etiología , Bronquiolitis Obliterante/patología , Bronquiolitis Obliterante/prevención & control , Recuento de Células , Método Doble Ciego , Volumen Espiratorio Forzado , Humanos , Inflamación/etiología , Inflamación/patología , Inflamación/prevención & control , Trasplante de Pulmón/efectos adversos , Trasplante de Pulmón/fisiología , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: The bronchiolitis obliterans syndrome (BOS) remains the major constraint on the long term success of lung transplantation. Neutrophils have been associated with fibrosing lung conditions and have been noted to be increased in the bronchoalveolar lavage (BAL) fluid of patients with BOS. METHODS: This study was undertaken to examine neutrophil accumulation in the BAL fluid, airway wall and lung parenchyma, as well as levels of interleukin (IL)-8 in the BAL fluid, in normal controls and lung transplant recipients with and without BOS. Bronchoscopic examination included endobronchial biopsy (EBB), BAL fluid, and transbronchial biopsy (TBB) sampling. Tissue neutrophils were identified by neutrophil elastase staining on 3 microm paraffin biopsy sections and quantified by computerised image analyser. IL-8 levels were measured in unconcentrated BAL fluid by ELISA. RESULTS: Compared with controls, airway wall neutrophilia was increased in both stable lung transplant recipients and those with BOS (p<0.05). BAL neutrophils and IL-8 levels were also increased in both groups of transplant recipients compared with controls (p<0.01), the levels being significantly higher in the BOS group (p<0.01). Neutrophil numbers in the lung parenchyma were not significantly different between the two groups of lung transplant recipients. CONCLUSION: Increased levels of neutrophils are present in the airway wall and BAL fluid of lung transplant recipients with and without BOS. BAL fluid levels of IL-8 are also increased, raising the possibility that neutrophils and/or IL-8 may play a part in the pathogenesis of BOS following lung transplantation.