Métastases pulmonaires: quelle place pour la chirurgie [Management pulmonary metastases: when operate?].

Thirty percent of patients suffering from malignant disease will develop pulmonary metastases. Effective chemotherapy is lacking for many of these tumors. Many studies suggest survival benefit in selected patients when pulmonary metastasectomy allows complete resection. Several operative approach may be offered in order to achieve complete resection and maximal lung sparring. Pre-operative workup must assess the control of the primary tumor and the possibility of performing complete resection. Minimally invasive approaches may offer better quality life and equivalent oncologic outcomes than open approach.

Ventilation-induced pulmonary vasodilatation in lambs with congenital diaphragmatic hernia is modulated by nitric oxide.

Endogenous nitric oxide (NO) mediates pulmonary vasodilatation at birth, but inhaled NO fails to reduce pulmonary vascular resistance (PVR) in newborns with congenital diaphragmatic hernia (CDH). This study was designed to investigate the effects of ventilation, and the nature of its endogenous mediator, in fetal lambs with experimental CDH. Investigations at 138 days of gestation showed that ventilation markedly decreased PVR. Inhibition of NO synthesis reduced ventilation-induced pulmonary vasodilatation in vivo and increased in vitro isometric tension of vascular rings. Ventilation therefore reduces PVR at birth in lambs with CDH, and endogenous NO seems to contribute to this reduction.

Pulmonary and systemic vascular dysfunction in young offspring of mothers with preeclampsia.

BACKGROUND: Adverse events in utero may predispose to cardiovascular disease in adulthood. The underlying mechanisms are unknown. During preeclampsia, vasculotoxic factors are released into the maternal circulation by the diseased placenta. We speculated that these factors pass the placental barrier and leave a defect in the circulation of the offspring that predisposes to a pathological response later in life. The hypoxia associated with high-altitude exposure is expected to facilitate the detection of this problem. METHODS AND RESULTS: We assessed pulmonary artery pressure (by Doppler echocardiography) and flow-mediated dilation of the brachial artery in 48 offspring of women with preeclampsia and 90 offspring of women with normal pregnancies born and permanently living at the same high-altitude location (3600 m). Pulmonary artery pressure was roughly 30% higher (mean+/-SD, 32.1+/-5.6 versus 25.3+/-4.7 mm Hg; P<0.001) and flow-mediated dilation was 30% smaller (6.3+/-1.2% versus 8.3+/-1.4%; P<0.0001) in offspring of mothers with preeclampsia than in control subjects. A strong inverse relationship existed between flow-mediated dilation and pulmonary artery pressure (r=-0.61, P<0.001). The vascular dysfunction was related to preeclampsia itself because siblings of offspring of mothers with preeclampsia who were born after a normal pregnancy had normal vascular function. Augmented oxidative stress may represent an underlying mechanism because thiobarbituric acid-reactive substances plasma concentration was increased in offspring of mothers with preeclampsia. CONCLUSIONS: Preeclampsia leaves a persistent defect in the systemic and the pulmonary circulation of the offspring. This defect predisposes to exaggerated hypoxic pulmonary hypertension already during childhood and may contribute to premature cardiovascular disease in the systemic circulation later in life.

Neuronal nitric oxide synthase does not contribute to the modulation of pulmonary vascular tone in fetal lambs with congenital diaphragmatic hernia (nNOS in CDH lambs).

AIM: The aim of this study was to determine the presence of the neuronal nitric oxide synthase (nNOS) in near full-term lambs with congenital diaphragmatic hernia (CDH) and its role in the modulation of pulmonary vascular basal tone. METHODS: We surgically created diaphragmatic hernia on the 85th day of gestation. On the 135th, catheters were used to measure pulmonary pressure and blood flow. We tested the effects of 7-nitroindazole (7-NINA), a specific nNOS antagonist and of N-nitro-L-arginine (L-NNA), a nonspecific nitric oxide synthase antagonist. In vitro, we tested the effects of the same drugs on isolated pulmonary vessels. The presence of nNOS protein in the lungs was detected by Western blot analysis. RESULTS: Neither 7-NINA nor L-NNA modified pulmonary vascular basal tone in vivo. After L-NNA injection, acetylcholine (ACh) did not decrease significantly pulmonary vascular resistance (PVR). In vitro, L-NNA increased the cholinergic contractile-response elicited by electric field stimulation (EFS) of vascular rings from lambs with diaphragmatic hernia. CONCLUSION: We conclude that nNOS protein is present in the lungs and pulmonary artery of near full-term lamb fetuses with diaphragmatic hernia, but that it does not contribute to the reduction of pulmonary vascular tone at birth

Pulmonary-artery pressure and exhaled nitric oxide in bolivian and caucasian high altitude dwellers

Rapport de synthèse : Plusieurs études suggèrent que les populations vivant en haute altitude sont mieux protégées contre l'hypertension pulmonaire hypoxique que celles originaires de la plaine. Cependant, les mécanismes sous jacents ne sont pas bien compris. Chez les Tibétains, la synthèse augmentée par le système respiratoire de monoxyde d'azote (NO) atténue l'hypertension pulmonaire hypoxique. Il a été spéculé que ce mécanisme pourrait représenter un mode généralisé d'adaptation à la haute altitude, mais il n'existe pas de preuve directe qui consume cette hypothèse. Nous avons donc mesuré la pression artérielle pulmonaire (par échocardiographie Doppler) ainsi que la concentration du NO dans l'air exhalé chez 34 Boliviens en bonne santé, nés et ayant toujours vécus en haute altitude (3600 m) et chez 34 Caucasiens apparentés pour l'âge et le sexe, nés en basse altitude mais vivant depuis de nombreuses années à cette même haute altitude (3600 mètres). La pression artérielle pulmonaire (24.3±5.9 vs. 24.7±4.9 mm Hg) et le NO exhalé (19.2±7.2 vs. 22.5±9.5 ppb) étaient similaires chez les Boliviens et les Caucasiens. Il n'y avait aucune corrélation entre la pression artérielle pulmonaire et le NO respiratoire dans les deux groupes. Ces résultats ne fournissent donc aucune évidence que les Boliviens nés en haute altitude sont mieux protégés contre l'hypertension pulmonaire hypoxique que les Caucasiens nés à basse altitude. Cela suggère que l'atténuation de l'hypertension pulmonaire par une synthèse accrue de NO respiratoire ne représente pas un mode universel d'adaptation des populations à la haute altitude. Abstract : There is evidence that high altitude populations may be better protected from hypoxic pulmonary hypertension than low altitude natives, but the underlying mechanism is incompletely understood. In Tibetans, increased pulmonary respiratory NO synthesis attenuates hypoxic pulmonary hypertension. It has been speculated that this mechanism may represent a generalized high altitude adaptation pattern, but direct evidence for this speculation is lacking. We therefore measured systolic pulmonary-artery pressure (Doppler echocardiography) and exhaled nitric oxide (NO) in 34 healthy, middle-aged Bolivian high altitude natives and in 34 age- and sex-matched, well-acclimatized Caucasian low altitude natives living at high altitude (3600 m). The mean ± SD systolic right ventricular to right arterial pressure gradient (24.3 ± 5.9 vs. 24.7 ± 4.9 mmHg) and exhaled NO (19.2 ± 7.2 vs. 22.5 ± 9.5 ppb) were similar in Bolivians and Caucasians. There was no relationship between ,pulmonary-artery pressure and respiratory NO in the two groups. These findings provide no evidence that Bolivian high altitude natives are better protected from hypoxic pulmonary hypertension than Caucasian low altitude natives and suggest that attenuation of pulmonary hypertension by increased respiratory NO synthesis may not represent a universal adaptation pattern in highaltitude populations.

Exaggerated pulmonary hypertension during mild exercise in chronic mountain sickness.

BACKGROUND: Chronic mountain sickness (CMS) is an important public health problem and is characterized by exaggerated hypoxemia, erythrocytosis, and pulmonary hypertension. While pulmonary hypertension is a leading cause of morbidity and mortality in patients with CMS, it is relatively mild and its underlying mechanisms are not known. We speculated that during mild exercise associated with daily activities, pulmonary hypertension in CMS is much more pronounced. METHODS: We estimated pulmonary artery pressure by using echocardiography at rest and during mild bicycle exercise at 50 W in 30 male patients with CMS and 32 age-matched, healthy control subjects who were born and living at an altitude of 3,600 m. RESULTS: The modest, albeit significant difference of the systolic right-ventricular-to-right-atrial pressure gradient between patients with CMS and controls at rest (30.3 +/- 8.0 vs 25.4 +/- 4.5 mm Hg, P 5 .002) became more than three times larger during mild bicycle exercise (56.4 +/- 19.0 vs 39.8 +/- 8.0 mm Hg, P < .001). CONCLUSIONS: Measurements of pulmonary artery pressure at rest greatly underestimate pulmonary artery pressure during daily activity in patients with CMS. The marked pulmonary hypertension during mild exercise associated with daily activity may explain why this problem is a leading cause of morbidity and mortality in patients with CMS.

Goodpasture's disease presenting with acute renal failure

A 15-year-old boy was admitted for vomiting, diarrhea, fatigue, crampy abdominal pain and oliguria. A renal failure was diagnosed (creatinine 2523 μmol/, urea 53,1 mmol/l) with severe aregenerative anemia (80 g/l), metabolic acidosis, hyperkalemia, elevated inflammatory markers and normal platelet count. A nephrotic proteinuria was noticed (350 g/mol). Patient's creatinine was normal 4 months before. The diagnosis of rapidly progressive glomerulonephritis was suspected. C3 and C4 were normal, ANA and ANCA were negative; anti-glomerular basement membrane antibody (anti-GBM) was positive (1/320) which lead to the diagnosis of Goodpasture's disease. Chest X-ray showed bilateral hilar infiltration and CT-scan revealed multiple alveolar haemorrhages, confirmed by broncho-alveolar lavage. Renal ultrasound showed swollen and hyperechogenous kidneys with loss of corticomedullary differentiation. Renal biopsy revealed a global extracapillary necrotising glomerulonephritis, with IgG lining the membrane at immunofluorescence. The patient was treated with continuous venovenous hemodia- filtration, plasmapheresis and immunosuppressive therapy (cyclophosphamid and corticoids) which lead to normalisation of anti-GBM level and favourable respiratory evolution with no sequelae. The renal evolution was unfavourable and the patient developed end stage renal disease and was treated with haemodialysis. Goodpasture's disease is an autoimmune process in which anti-GBM are produced against collagen IV present in the kidneys and pulmonary alveolae, resulting in acute or rapidly progressive glomerulonephritis and altering the pulmonary alveolae. It is a rare disease concerning mostly infants and young adults. Clinical presentation consists in an acute renal failure with proteinuria. Pulmonary symptoms (60-70% of the total cases) are dyspnea, cough, and haemoptysis. Diagnosis is made with the dosage of immunological anti-GBM and with renal biopsy. Factors of poor prognosis are initial oliguria, alteration of >50% of the glomerulus, very high creatinine or need of dialysis. Anti-GBM dosage is used for follow up. Patients are treated with immunosuppressive therapy for 6 to 9 months and plasmapheresis. Few recurrences are seen. Goodpasture's disease should be evoqued whenever a young patient is seen with glomerulonephritis, especially if pulmonary abnormalities are present. The disease requires an aggressive treatment in order to prevent respiratory and kidney failure.

Airway epithelial IL-15 transforms monocytes into dendritic cells.

IL-15 has recently been shown to induce the differentiation of functional dendritic cells (DCs) from human peripheral blood monocytes. Since DCs lay in close proximity to epithelial cells in the airway mucosa, we investigated whether airway epithelial cells release IL-15 in response to inflammatory stimuli and thereby induce differentiation and maturation of DCs. Alveolar (A549) and bronchial (BEAS-2B) epithelial cells produced IL-15 spontaneously and in a time- and dose-dependent manner after stimulation with IL-1beta, IFN-gamma, or TNF-alpha. Airway epithelial cell supernatants induced an increase of IL-15Ralpha gene expression in ex vivo monocytes, and stimulated DCs enhanced their IL-15Ralpha gene expression up to 300-fold. Airway epithelial cell-conditioned media induced the differentiation of ex vivo monocytes into partially mature DCs (HLA-DR+, DC-SIGN+, CD14+, CD80-, CD83+, CD86+, CCR3+, CCR6(+), CCR7-). Based on their phenotypic (CD123+, BDCA2+, BDCA4+, BDCA1(-), CD1a-) and functional properties (limited maturation upon stimulation with LPS and limited capacity to induce T cell proliferation), these DCs resembled plasmacytoid DCs. The effects of airway epithelial cell supernatants were largely blocked by a neutralizing monoclonal antibody to IL-15. Thus, our results demonstrate that airway epithelial cell-conditioned media have the capacity to differentiate monocytes into functional DCs, a process substantially mediated by epithelial-derived IL-15.

Pseudomonas aeruginosa et maladie broncho-pulmonaire chronique obstructive [Pseudomonas aeruginosa in chronic obstructive pulmonary disease].

The role of Pseudomonas aeruginosa isolated in sputum cultures from adults with obstructive chronic pulmonary disease (COPD) is not well known. However, this pathogen has many factors of virulence and is responsible for several clinical manifestations in this setting. Isolation of a new strain of Pseudomonas is associated with a significant risk of exacerbation of the COPD and its prevalence depends on the severity of the COPD. The role of Pseudomonas among patients with COPD apart from exacerbations is less clear, but it could be responsible for an ignition for the airways and progression for the disease. Currently, the relevance of a prophylactic antibiotic therapy has not yet been demonstrated in COPD holders of Pseudomonas.

Lésions cutanées et infiltrats pulmonaires d'évolution défavorable sans cause infectieuse [Progressive cutaneous and pulmonary lesions without infectious etiology: two cases reports of sweet syndrome with pulmonary involvement].

Sweet syndrome is a non infectious febrile disease with a neutrophilic infiltrate of dermis. Extracutaneous involvement can occur. We report two cases of Sweet syndrome with cutaneous and pulmonary involvement and give a short review of the literature of pulmonary involvement in Sweet syndrome.

Sniff nasal inspiratory pressure in patients with chronic obstructive pulmonary disease.

In subjects with normal lung mechanics, inspiratory muscle strength can be reliably and easily assessed by the sniff nasal inspiratory pressure (SNIP), which is the pressure measured in an occluded nostril during a maximal sniff performed through the contralateral nostril. The aim of this study was to assess the validity of the SNIP in patients with chronic obstructive pulmonary disease (COPD), where pressure transmission from alveoli to upper airways is likely to be dampened. Twenty eight patients with COPD were studied (mean forced expiratory volume in one second (FEV1) = 36% of predicted). The SNIP and the sniff oesophageal pressure (sniff Poes) were measured simultaneously during maximal sniffs, and were compared to the maximal inspiratory pressure obtained against an occlusion (MIP). All measurements were performed from functional residual capacity in the sitting position. The ratio SNIP/sniff Poes was 0.80, and did not correlate with the degree of airflow limitation. The ratio MIP/sniff Poes was 0.87, and the ratio SNIP/MIP was 0.97. Inspiratory muscle weakness, as defined by a low sniff Poes, was present in 17 of the 28 patients. A false diagnosis of weakness was made in eight patients when MIP was considered alone, in four when SNIP was considered alone, and in only three patients when MIP and SNIP were combined. We conclude that both the sniff nasal inspiratory pressure and the maximal inspiratory pressure moderately underestimate sniff oesophageal pressure in chronic obstructive pulmonary disease. Although suboptimal in this condition, the sniff nasal inspiratory pressure appears useful to complement the maximal inspiratory pressure for assessing inspiratory muscle strength in patients with chronic obstructive pulmonary disease.

Nonthrombotic pulmonary embolism.

OBJECTIVE: The purpose of this essay is to highlight the clinical features and imaging findings associated with different types of nonthrombotic pulmonary embolism. CONCLUSION: Nonthrombotic pulmonary embolism is an infrequent condition with various causes that can be life-threatening pathologic conditions. The entity presents a diagnostic challenge because of the low specificity of clinical symptoms and imaging signs. Awareness of the imaging features of nonthrombotic pulmonary embolism facilitates correct diagnosis and leads to appropriate patient care.

Low-dose theophylline enhances the anti-inflammatory effects of steroids during exacerbations of chronic obstructive pulmonary disease

ABSTRACT Background: Chronic obstructive pulmonary disease (COPD) is characterised by an abnormal inflammatory response mainly to cigarette smoke that flares up during exacerbations of the disease (ECOPD). Reduced activity of histone deacetylases (HDAC) contributes to enhanced inflammation in stable COPD. It was hypothesised that HDAC activity is further reduced during ECOPD and that theophylline, an HDAC activator, potentiates the antiinflammatory effect of steroids in these patients. A study was performed to investigate HDAC activity during ECOPD and the effects of theophylline on the anti-inflammatory effects of steroids in a randomised single-blind controlled study. Methods: 35 patients hospitalised with ECOPD and treated according to international guidelines (including systemic steroids) were randomised to receive or not to receive low-dose oral theophylline (100 mg twice daily). Before treatment and 3 months after discharge, HDAC and nuclear factor-kB (NF-kB) activity in sputum macrophages, the concentration of nitric oxide in exhaled air (eNO) and total antioxidant status (TAS), tumour necrosis factor a (TNFa), interleukin (IL)-6 and IL8 levels in sputum supernatants were measured. Results: Patients receiving standard therapy showed decreased NF-kB activity, eNO concentration and sputum levels of TNFa, IL6 and IL8, as well as increased TAS during recovery of ECOPD, but HDAC activity did not change. The addition of low-dose theophylline increased HDAC activity and further reduced IL8 and TNFa concentrations. Conclusions: During ECOPD, low-dose theophylline increases HDAC activity and improves the anti-inflammatory effects of steroids.

Imaging for trans-catheter pulmonary stent-valve implantation without angiography: role of intravascular ultrasound.

Patients with stenosed biologic pulmonary conduits require redo cardiac surgery to prevent severe right ventricular dysfunction. Following the latest trends, the trans-catheter pulmonary stent-valve implantation represents a new fascinating alternative carrying a lower operative risk, compared with the standard open-heart re-intervention. Traditionally, the pulmonary stent valve is positioned off pump, under fluoroscopic control, and requires angiographies. However, alternative tools not requiring contrast injections for the intra-operative cardiac imaging have to be also considered strongly. The usefulness of intravascular ultrasound for the positioning of aortic endoprosthesis has already been proven in previous reports and, following the same principle, we have started to routinely implant balloon-expandable stent valves (Edwards Sapien? THV) in stenosed pulmonary valve conduits using intravascular ultrasound for the stent-valve positioning without angiography. We describe the intra-operative intravascular imaging technique with technical details.