Administration of growth hormone to underweight patients with chronic obstructive pulmonary disease. A prospective, randomized, controlled study.

Patients with chronic obstructive pulmonary disease (COPD) often develop weight loss, which is associated with increased mortality. Recombinant human growth hormone (rhGH) treatment has been proposed to improve nitrogen balance and to increase muscle strength in these patients. The aim of this study was to assess the effects of rhGH administration on the nutritional status, resting metabolism, muscle strength, exercise tolerance, dyspnea, and subjective well-being of underweight patients with stable COPD. Sixteen patients attending a pulmonary rehabilitation program (age: 66 +/- 9 yr; weight: 77 +/- 7% of ideal body weight; FEV1: 39 +/- 13% of predicted) were randomly treated daily with either 0.15 IU/kg rhGH or placebo during 3 wk in a double-blind fashion. Measurements were made at the beginning (DO) and at the end (D21) of treatment and 2 mo later (D81). Body weight was similar in the two groups during the study, but lean body mass was significantly higher in the rhGH group at D21 (p < 0.01) and D81 (p < 0.05). The increase in lean body mass was 2.3 +/- 1.6 kg in the rhGH group and 1.1 +/- 0.9 kg in the control group at D21 and 1.9 +/- 1.6 kg in the rhGH group and 0.7 +/- 2.1 kg in the control group at D81. At D21, the resting energy expenditure was increased in the rhGH group (107.8% of DO, p < 0.001 compared with the control group). At D21 and D81, the changes in maximal respiratory pressures, handgrip strength, maximal exercise capacity, and subjective well-being were similar in the two groups. At D21, the 6-min walking distance decreased in the rhGH group (-13 +/- 31%) and increased in the control group (+10 +/- 14%; p < 0.01). We conclude that the daily administration of 0.15 IU/kg rhGH during 3 wk increases lean body mass but does not improve muscle strength or exercise tolerance in underweight patients with COPD.

An unusual cause of hemoptysis--aberrant origin of the left pulmonary artery from the ascending aorta in the adult.

Aberrant origin of a pulmonary artery from the ascending aorta is an uncommon congenital vascular malformation with poor survival without surgery. In this case report, we describe the unusual late diagnosis of this congenital malformation in an otherwise asymptomatic young man presenting with mild hemoptysis. We review the natural and modified history of this defect and the relevant aspects of follow-up in adult life.

Hipertensión y edema pulmonar de altura. Rol de la disfunción endotelial y de la programación fetal [Pulmonary hypertension and lung edema at high altitude. Role of endothelial dysfunction and fetal programming].

High altitude constitutes an exciting natural laboratory for medical research. While initially, the aim of high-altitude research was to understand the adaptation of the organism to hypoxia and find treatments for altitude-related diseases, over the past decade or so, the scope of this research has broadened considerably. Two important observations led to the foundation for the broadening of the scientific scope of high-altitude research. First, high-altitude pulmonary edema (HAPE) represents a unique model which allows studying fundamental mechanisms of pulmonary hypertension and lung edema in humans. Secondly, the ambient hypoxia associated with high-altitude exposure facilitates the detection of pulmonary and systemic vascular dysfunction at an early stage. Here, we review studies that, by capitalizing on these observations, have led to the description of novel mechanisms underpinning lung edema and pulmonary hypertension and to the first direct demonstration of fetal programming of vascular dysfunction in humans.

Distal trisomy 14 (q24 --> qter) and aorto-pulmonary window: a case report and review of the literature.

A newborn female with partial trisomy for the distal part of the long arm of the chromosome 14 (14q24 --> qter) resulting from a paternal balanced translocation (3;14) is described. We compare her phenotype with eight other individuals with trisomy 14q24 --> qter.

Troponin-based risk stratification of patients with acute nonmassive pulmonary embolism: systematic review and metaanalysis.

BACKGROUND: Controversy exists regarding the usefulness of troponin testing for the risk stratification of patients with acute pulmonary embolism (PE). We conducted an updated systematic review and a metaanalysis of troponin-based risk stratification of normotensive patients with acute symptomatic PE. The sources of our data were publications listed in Medline and Embase from 1980 through April 2008 and a review of cited references in those publications. METHODS: We included all studies that estimated the relation between troponin levels and the incidence of all-cause mortality in normotensive patients with acute symptomatic PE. Two reviewers independently abstracted data and assessed study quality. From the literature search, 596 publications were screened. Nine studies that consisted of 1,366 normotensive patients with acute symptomatic PE were deemed eligible. Pooled results showed that elevated troponin levels were associated with a 4.26-fold increased odds of overall mortality (95% CI, 2.13 to 8.50; heterogeneity chi(2) = 12.64; degrees of freedom = 8; p = 0.125). Summary receiver operating characteristic curve analysis showed a relationship between the sensitivity and specificity of troponin levels to predict overall mortality (Spearman rank correlation coefficient = 0.68; p = 0.046). Pooled likelihood ratios (LRs) were not extreme (negative LR, 0.59 [95% CI, 0.39 to 0.88]; positive LR, 2.26 [95% CI, 1.66 to 3.07]). The Begg rank correlation method did not detect evidence of publication bias. CONCLUSIONS: The results of this metaanalysis indicate that elevated troponin levels do not adequately discern normotensive patients with acute symptomatic PE who are at high risk for death from those who are at low risk for death.

Association of biomarkers of lipid modification with functional and morphological indices of coronary stenosis severity in stable coronary artery disease.

Biomarkers of blood lipid modification and oxidative stress have been associated with increased cardiovascular morbidity. We sought to determine whether these biomarkers were related to functional indices of stenosis severity among patients with stable coronary artery disease. We studied 197 consecutive patients with stable coronary artery disease due to single vessel disease. Fractional flow reserve (FFR) ≤ 0.80 was assessed as index of a functionally significant lesion. Serum levels of secretory phospholipase A2 (sPLA2) activity, secretory phospholipase A2 type IIA (sPLA2-IIA), myeloperoxydase (MPO), lipoprotein-associated phospholipase A2 (Lp-PLA2), and oxidized low-density lipoprotein (OxLDL) were assessed using commercially available assays. Patients with FFR > 0.8 had higher sPLA2 activity, sPLA2 IIA, and OxLDL levels than patients with FFR ≤ 0.8 (21.25 [16.03-27.28] vs 25.85 [20.58-34.63] U/mL, p < 0.001, 2.0 [1.5-3.4] vs 2.6 [2.0-3.4] ng/mL, p < 0.01; and 53.0 [36.0-71.0] vs 64.5 [50-89.25], p < 0.001 respectively). Patients with FFR > 0.80 had similar Lp-PLA2 and MPO levels versus those with FFR ≤ 0.8. sPLA2 activity, sPLA2 IIA significantly increased area under the curve over baseline characteristics to predict FFR ≤ 0.8 (0.67 to 0.77 (95 % confidence interval [CI]: 0.69-0.85) p < 0.01 and 0.67 to 0.77 (95 % CI: 0.69-0.84) p < 0.01, respectively). Serum sPLA2 activity as well as sPLA2-IIA level is related to functional characteristics of coronary stenoses in patients with stable coronary artery disease.

Should pulmonary embolism be suspected in exacerbation of chronic obstructive pulmonary disease?

BACKGROUND: The cause of acute exacerbation of chronic obstructive pulmonary disease (COPD) is often difficult to determine. Pulmonary embolism may be a trigger of acute dyspnoea in patients with COPD. AIM: To determine the prevalence of pulmonary embolism in patients with acute exacerbation of COPD. METHODS: 123 consecutive patients admitted to the emergency departments of two academic teaching hospitals for acute exacerbation of moderate to very severe COPD were included. Pulmonary embolism was investigated in all patients (whether or not clinically suspected) following a standardised algorithm based on d-dimer testing, lower-limb venous ultrasonography and multidetector helical computed tomography scan. RESULTS: Pulmonary embolism was ruled out by a d-dimer value <500 microg/l in 28 (23%) patients and a by negative chest computed tomography scan in 91 (74%). Computed tomography scan showed pulmonary embolism in four patients (3.3%, 95% confidence interval (CI), 1.2% to 8%), including three lobar and one sub-segmental embolisms. The prevalence of pulmonary embolism was 6.2% (n = 3; 95% CI, 2.3% to 16.9%) in the 48 patients who had a clinical suspicion of pulmonary embolism and 1.3% (n = 1; 95% CI, 0.3% to 7.1%) in those not suspected. In two cases with positive computed tomography scan, the venous ultrasonography also showed a proximal deep-vein thrombosis. No other patient was diagnosed with venous thrombosis. CONCLUSIONS: The prevalence of unsuspected pulmonary embolism is very low in patients admitted in the emergency department for an acute exacerbation of their COPD. These results argue against a systematic examination for pulmonary embolism in this population.

Chronic obstructive pulmonary disease in never-smoking animal farmers working inside confinement buildings

BACKGROUND: In animal farming, respiratory disease has been associated with indoor air contaminants and an excess in FEV1 decline. Our aim was to determine the characteristics and risk factors for chronic obstructive pulmonary disease (COPD) in never-smoking European farmers working inside animal confinement buildings. METHODS: A sample of participants in the European Farmers' Study was selected for a cross-sectional study assessing lung function and air contaminants. Dose-response relationships were assessed using logistic regression models. RESULTS: COPD was found in 18 of 105 farmers (45.1 SD 11.7 years) (17.1%); 8 cases (7.6%) with moderate and 3 cases (2.9%) with severe disease. Dust and endotoxin showed a dose-response relationship with COPD, with the highest prevalence of COPD in subjects with high dust (low=7.9%/high=31.6%) and endotoxin exposure (low=10.5%/high=20.0%). This association was statistically significant for dust in the multivariate analysis (OR 6.60, 95% CI 1.10-39.54). CONCLUSION: COPD in never-smoking animal farmers working inside confinement buildings is related to indoor dust exposure and may become severe. [Authors]

Pulmonary involvement in Fabry disease: Overview and perspectives.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by deficiency of alpha-galactosidase A, which leads to storage of sphingolipids in virtually all human cells and consequently to organ dysfunction. Pulmonary involvement is still debated. But, obstructive lung disease is up to ten times more prevalent in patients with FD compared to general public. Also, an accelerated decline in forced expiratory volume in one second (FEV1) over time was observed in these patients. Lysosomal storage of glycosphingolipids is considered leading to small airway disease via hyperplasia of the bronchiolar smooth muscle cells. Larger airways may become involved with ongoing disease process. There is no evidence for involvement of the lung interstitium in FD. The effect of enzyme replacement therapy on respiratory involvement remains to be determined in large, prospective controlled trials.

Gadolinium-enhanced pulmonary magnetic resonance angiography in the diagnosis of acute pulmonary embolism: a prospective study on 48 patients.

OBJECTIVE: Gadolinium-enhanced pulmonary magnetic resonance angiography (MRA) can be an option in patients with a history of previous adverse reaction to iodinated contrast material and renal insufficiency. Radiation is also avoided. The aim of this study is to prospectively compare the diagnostic value of MRA with that of a diagnostic strategy, taking into account catheter angiography, computed tomography angiography (CTA), and lung scintigraphy [ventilation-perfusion (VQ)]. MATERIAL AND METHODS: Magnetic resonance angiography was done in 48 patients with clinically suspected pulmonary embolism (PE) using fast gradient echo coronal acquisition with gadolinium. Interpretation was done with native coronal images and multiplanar maximum intensity projection reconstructions. Results were compared to catheter angiography (n=15), CTA (n=34), VQ (n=45), as well as 6-12 months clinical follow-ups, according to a sequenced reference tree. RESULTS: The final diagnosis of PE was retained in 11 patients (23%). There were two false negatives and no false positive results with MRA. Computed tomography angiography resulted in no false negatives or false positives. Magnetic resonance angiography had a sensitivity of 82% and a specificity of 100%. CONCLUSION: In our study, pulmonary MRA had a sensitivity of 82% and a specificity of 100% for the diagnosis of PE, with slightly less sensitivity than CTA. In the diagnostic algorithm of PE, pulmonary MRA should be considered as an alternative to CTA when iodine contrast injection or radiation is a significant matter.

Endothelin-1 does not mediate the endothelium-dependent hypoxic contractions of small pulmonary arteries in rats.

Various pulmonary artery preparations in vitro demonstrate sustained endothelium-dependent contractions upon hypoxia. To determine whether endothelin-1 could mediate this phenomenon, we examined the effect of bosentan, a new antagonist of both the ETA and ETB subtypes of the endothelin receptor. Small (300 pm) pulmonary arteries from rats were mounted on a myograph, precontracted with prostaglandin F2 alpha and exposed to hypoxia (PO2, 10 to 15 mm Hg, measured on-line) for 45 min. Endothelium-intact control rings exhibited a biphasic response, with a transient initial vasoconstriction (phase 1) followed by a second slowly developing sustained contraction (phase 2). Expressed in percent of the maximal response to 80 mmol/L KCl, the amplitudes of phase 1 (peak tension) and 2 (tension after 45 min of hypoxia) averaged 37 +/- 12% and 17 +/- 14%, respectively (n = 11). In endothelium-denuded rings, phase 1 persisted while the amplitude of phase 2 was reduced to 2 +/- 12% (p < 0.05, n = 8), showing the endothelium dependence of this contraction. Neither phase was significantly decreased in rings treated with 10(-5) mmol/L bosentan (38 +/- 15% and 17 +/- 12%, respectively, n = 6). The PO2 threshold for onset of hypoxic contraction was not significantly different among these three groups and averaged 32 +/- 24 mm Hg. In a separate experiment, we assessed the inhibitory effect of 10(-5) mol/L bosentan on the response to 10(-8) mol/L endothelin-I. Rings treated for 45 min with 10(-8) mol/L endothelin-1 alone exhibited a maximal contraction of 75 +/- 27% (n = 6). This was reduced to 4 +/- 17% (p < 0.01, n = 6) in rings treated with both 10(-8) mol/L endothelin-1 and 10(-5) mol/L bosentan. We conclude that complete blockade of all endothelin receptor subtypes has no effect on either endothelium-dependent or -independent hypoxic contractions in this preparation. This suggests that endothelial factors other than endothelin-I mediate the acute hypoxic contractions of small pulmonary arteries in the rat.

Successful bilateral lung transplantation after previous pneumonectomy

Objective: To present the feasibility of bilateral lung transplantation after previously performed pneumonectomy.Methods: A 32 years old women underwent right pneumonectomy for bronchiectasis-related destroyed lung. Eight months later, she developed a vascular post-pneumonectomy syndrome and underwent realigning of the mediastinum by an intrathoracic expander that was complicated by an adult respiratory distress syndrome of the left lung requiring mechanical ventilation, arterio-venous CO2 removal (Novalung) and finally bilateral lung transplantation. Via clamshell incision, the post-pneumonectomy cavity was dissected and the superior vena cava (SVC) and carina were exposed. The pulmonary vessel stumps were dissected intrapericardically after realization of a right-sided hemi-pericardectomy. Extracorporeal circulation was started after central cannulation of the aorta and the inferior vena cava. A right upper lobe sleeve resection of the donor lung was performed. The intermediate bronchus was then implanted in the dissected recipient carina after realization of a hilar release maneuver. The right pulmonary artery was clamped between SVC andthe ascending aorta followed by end -to-end anastomosis of the donor and recipient artery and left atrial cuffs, respectively. Satisfactory graft function allowed decanulation and standard transplantation of the left lung without extracorporeal circulation.Results: Bronchoscopy and trans-esophageal echocardiography demonstrated a patent airway and vascular anastomoses without stenosis. Follow-up revealed excellent gas exchanges, no airway complications and well-functioning grafts on both sides with right-sided ventilation and perfusion two months after transplantation of 37% and 22%, respectively.Conclusion: This is to our knowledge the first report of successful bilateral lung transplantation after previous pneumonectomy unrelated to transplantation.

Multiple pulmonary artery aneurysms in tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a rare genetic disorder characterised by multiple hamartomas, caused by inactivating mutations of the TSC1/TSC2 tumour suppressor genes. Classical pulmonary involvement in tuberous sclerosis complex (TSC) consists of lymphangioleiomyomatosis and/or multiple micronodular pneumocyte hyperplasia (MMPH). Association of TSC with pulmonary artery aneurysm (PAA) has been only exceptionally described. We report here the first case of TSC with multiple PAA in combination with MMPH, cardiac rhabdomyomas and bone, skin and brain involvement.

Partial cricotracheal resection for congenital subglottic stenosis in children: the effect of concomitant anomalies.

OBJECTIVE: To review the surgical outcomes of partial cricotracheal resection in children with severe congenital subglottic stenosis and define the effect of concomitant anomalies or syndromes affecting outcome. METHODS: Forty-one children with subglottic stenosis of congenital and mixed (acquired on congenital) etiologies who underwent partial cricotracheal resection were identified from a prospectively collected database. Children with congenital subglottic stenosis and concomitant anomalies/syndromes were compared to children with congenital subglottic stenosis with no syndromes or concomitant anomalies. Operation-specific decannulation rates and complication rates were the primary outcome measures. We performed a two-sample test of proportion using the STATA-10 software for categorical variables to detect differences in proportions. Significance was set at p value<0.05. RESULTS: Twenty-seven (66%) of 41 children had concomitant anomalies/syndromes and 14 (34%) had congenital subglottic stenosis without concomitant anomalies/syndromes. Four patients needed revision surgery in the concomitant anomaly group and two patients needed revision surgery in the non concomitant anomaly group before achieving decannulation. The operation-specific decannulation rate in the concomitant anomaly group was 85% and 86% in the non anomaly group. When compared to children without concomitant anomaly, children with concomitant anomalies were more likely to have delayed decannulation following partial cricotracheal resection. However, this difference was not found to be statistically significant. The complication and operation-specific decannulation rates after partial cricotracheal resection were comparable to children without concomitant anomalies. Mortality rate was 11% (three of 27 patients) in the group with associated congenital anomalies or syndromes. Two patients succumbed to the primary pathology and one patient died due to tracheostomy-tube obstruction. There was no post-operative death in the non anomaly group. CONCLUSION: Partial cricotracheal resection can be done safely and effectively in children with concomitant anomalies/syndromes to achieve decannulation. The post-operative course may be prolonged but the decannulation and the complication rates are comparable to those children with congenital subglottic stenosis without concomitant anomalies.

Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes.

Background Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes. Methods To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomarkers of systemic and bronchial inflammation, sputum microbiology, CT of the thorax and echocardiography were assessed. COPD groups were identified by partitioning cluster analysis and validated prospectively against cause-specific hospitalisations and all-cause mortality during a 4 year follow-up. Results Three COPD groups were identified: group 1 (n ¼ 126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV 1 ) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n ¼ 125, 69 years) showed milder airflow limitation (FEV 1 63% predicted); and group 3 (n ¼ 91, 67 years) combined a similarly milder airflow limitation (FEV 1 58% predicted) with a high proportion of obesity, cardiovascular disorders, iabetes and systemic inflammation. During follow-up, group 1 had more frequent hospitalisations due to COPD (HR 3.28, p < 0.001) and higher all-cause mortality (HR 2.36, p ¼ 0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p ¼ 0.014). Conclusions In patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated:"severe respiratory COPD","moderate respiratory COPD", and"systemic COPD'