Laurent Tetu

Pulmonary hypertension in antisynthetase syndrome: prevalence, aetiology and survival.

Antisynthetase syndrome is characterised by the association of interstitial lung disease and myositis with different anti-tRNA-synthetase antibodies. The occurrence, aetiology and prognosis of pulmonary hypertension have not yet been evaluated. Among 203 consecutive patients, transthoracic echocardiogram and right heart catheterisation results were retrospectively analysed in the light of clinico-biological, morphological and functional parameters. Definitions of pulmonary hypertension were based on the European Society of Cardiology/European Respiratory Society 2009 guidelines, with severe pulmonary hypertension being defined by a mean pulmonary arterial pressure >35 mmHg. Pulmonary hypertension was suspected by transthoracic echocardiogram in 47 (23.2%) cases, corresponding to pulmonary hypertension “possible” (n=27, 13.3%) or “likely” (n=20, 9.9%). Right heart catheterisation was performed in 21 patients, excluding pulmonary hypertension in five and confirming pre-capillary pulmonary hypertension in 16 (7.9%). Although related to interstitial lung disease in all cases, pre-capillary pulmonary hypertension was severe in 13 (81.3%) patients (mean±sd pulmonary arterial pressure 46±9 mmHg), frequently associated with low cardiac index (mean±sd 2.3±0.8 L·min−1·m−2) and high forced vital capacity/diffusing capacity of the lung for carbon monoxide ratio (2.5±0.6). Pulmonary hypertension was significantly associated with a lower survival rate (p<0.001), with a 3-year survival rate of 58%. The occurrence of pulmonary hypertension in antisynthetase syndrome is significant and dramatically worsens the prognosis. Although systematically associated with interstitial lung disease, pulmonary hypertension was usually severe, suggesting a specific pulmonary vascular involvement. PH in antisynthetase syndrome significantly worsens the prognosis, suggesting a specific pulmonary vascular involvement http://ow.ly/okXyG

Assessment of Aspergillus sensitization or persistent carriage as a factor in lung function impairment in cystic fibrosis patients

Background: Cystic fibrosis (CF) patients presenting with persistent carriage of, or sensitization to, Aspergillus fumigatus are often treated with antifungal therapies because the presence of the fungus is commonly thought to impede lung function, even in the absence of allergic bronchopulmonary aspergillosis (ABPA). The aim of this study was to assess Aspergillus-related status modulating the forced expiratory volume in 1 s (FEV1) of CF patients. Methods: From 1995 to 2007, 251 patients were evaluated. Demographic data, cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations, body mass index, and FEV1 were recorded. The presence of A. fumigatus and Pseudomonas aeruginosa in sputum and the levels of A. fumigatus precipitin, total IgE (t-IgE), and specific anti-A. fumigatus IgE (Af-IgE) were determined. Patients were divided into 3 groups: (1) ABPA: A. fumigatus precipitin ≥3 lines, Af-IgE > 0.35 IU/ml, and t-IgE ≥500 IU/ml; (2) sensitization: Af-IgE > 0.35 IU/ml but t-IgE < 500 IU/ml; and (3) persistent carriage: Af-IgE ≤ 0.35 IU/ml with either an A. fumigatus persistent positive culture or an A. fumigatus precipitin ≥3 lines, provided this serological finding had been found associated with at least 1 A. fumigatus-positive culture. The remaining patients represented the control group. A multivariate analysis was carried out with FEV1 as the outcome variable. Results: ABPA, sensitization, and persistent carriage were significantly associated with a larger decline in FEV1 compared with the control group, with odds ratios of 15.9, 14.9, and 10.7, respectively. This association was independent of other associated factors (P. aeruginosa transient detection, age, being underweight, and low FEV1 at baseline). Conclusions: In addition to ABPA, sensitization and persistent carriage appear to have an impact on pulmonary function in CF patients.

Aspergillus sensitization or carriage in cystic fibrosis patients.

Background: Aspergillus fumigatus (Af) sensitization and persistent carriage are deleterious to lung function, but no consensus has been reached defining these medical entities. This work aimed to identify possible predictive factors for patients who become sensitized to Af, compared with a control group of non-sensitized Af carriers. Methods: Between 1995 and 2007, 117 pediatric patients were evaluated. Demographic data, CFTR gene mutations, body mass index and FEV1 were recorded. The presence of Af in sputum, the levels of Af-precipitin, total IgE (t-IgE) and specific IgE to Af (Af-IgE) were determined. Patients were divided into 2 groups: (1) “sensitization”: level of Af-IgE > 0.35 IU/mL with t-IgE level < 500 IU/mL and (2) “persistent or transient carriage”: Af-IgE level ⩽ 0.35 IU/mL with either an Af transient or persistent positive culture. A survival analysis was performed with the appearance of Af-IgE in serum as an outcome variable. Results: Severe mutation (hazard ratio = 3.2), FEV1 baseline over 70% of theoretical value (hazard ratio = 4.9), absence of Pa colonization, catalase activity and previous azithromycin administration (hazard ratio = 9.8, 4.1 and 1.9, respectively) were predictive factors for sensitization. We propose a timeline of the biological events and a tree diagram for risk calculation. Conclusions: Two profiles of cystic fibrosis patients can be envisaged: (1) patients with nonsevere mutation but low FEV1 baselines are becoming colonized with Af or (2) patients with high FEV1 baselines who present with severe mutation are more susceptible to the Af sensitization and then to the presentation of an allergic bronchopulmonary aspergillosis event.

Determination of Cardiac Output in Pulmonary Hypertension Using Impedance Cardiography

Background: Cardiac output (CO) is a prognostic factor in pulmonary hypertension (PH). Right heart catheterisation using the direct Fick method or thermodilution (TD) is the reference technique for CO measurement. Impedance cardiography (IPc) is a known non-invasive method of measuring CO. Objectives: In our study, we assume that the measurement of CO by IPc using the PHYSIOFLOW® system is as accurate as TD or using the direct Fick method in patients with PH in group 1 or group 4. Methods: A total of 75 patients were enrolled in a prospective study carried out at the hypertension reference centre of Toulouse University Hospital. Right heart catheterisation was performed for the diagnosis or follow-up of the disease. CO was measured using the Fick method, TD, and IPc simultaneously. A Bland-Altman analysis was plotted. Results: CO was 5.7 ± 1.9 L/min as measured by the Fick method, 5.4 ± 1.5 L/min by TD, and 5.5 ± 1.7 L/min by IPc. The bias between CO measurements by IPc and the direct Fick method was 0.149 L/min (95% CI, –0.298 to 0.596). The bias between CO measurements by IPc and the TD method was –0.153 L/min (95% CI, –0.450 to 0.153). The correlation decreased with the more extreme CO values (< 3 L/min or > 7 L/min). A few factors changed the agreement between measurements (BMI or membership in group 4). Conclusion: To conclude, this study shows that the measurement of CO by IPc in PH patients is reliable compared to the direct Fick method and TD obtained by right heart catheterisation. This accuracy decreases for extreme CO values.

Accuracy of impedance cardiography to measure cardiac output at rest in pulmonary hypertension

Introduction: Cardiac output (CO) is one of the most important prognostic factor in PH and is required for the assessment of treatment response. CO is measured invasively by right heart catheterization by thermodilution or the Fick method. Impedance cardiography (IP) measures CO and is noninvasive, simple and provides immediate results. Objectives: The main objective of this feasibility study was to assess the accuracy of of CO measures performed IP compared to the Fick method in selected patients treated for PH (Group 1 or 4). Secondary objectives were to evaluate the accuracy of CO evaluation by IP compared to thermodilution and to determine the factors that may affect the measures. Methods: Patients were recruited from the cohort of the Competence Center PH of Midi-Pyrenees, France. The three techniques (Fick, thermodilution and IP) were realized at the same time during right heart catheterization performed in the patient follow up. All patients had confirmed PH from Group 1 or group 4. Results: We had recruited 37 subjects in the study. (31 patients group 1 and 6 patients group 4). The CO measured by IP correlates with the CO measured by the Fick method: ρ=0.62 CI 95% [0.3064; 0.8124] (P Conclusion: This pilot study validates the measurement of CO by IP in patients with PH (group 1 or 4). This suggests a potential role of the non-invasive IP in the follow up of PH patients.

0569: Platypnea orthodeoxia syndrome: focus on predisposing anatomical factors

Platypnea orthodeoxia syndrome (POS) is a rare situation with hypoxia and breathlessness varying between upright and recumbent position. A mechanical inter-atrial septum distortion, causing redirection of flow from the right to the left atrium through a patent foramen ovale (PFO), despite normal pulmonary pressure, is suggested to explain POS. Prevalence of predisposing anatomical factors remain little known. Methods All patients who underwent a PFO closure for a POS were retrospectively included from 2 CHU. Aetiologies were investigated. Results 67 patients (Median age 72 y.o., interquartile 61-80; 58.2% men) were included. All patients had dyspnea (76.2% NYHA III or IV, 53.7% under oxygen-therapy). The remaining patients had a refractory hypoxemia (38.2%) without POS. The most frequent predisposing anatomical factor was an enlarged or unwound aorta (n=29, 43.3% 95CI 31.2-56.0) with an aortic aneurysm in 25 patients (37.3%, 95CI 25.8-50.0). Other factors identified were pneumonectomy (n=8, 11.9% CI95 5.3-22.2), a history of cardiac surgery (n=7, 10.5%, 95CI 4.3-20.3), mechanical ventilation (n=6, 9.0% 95CI 3.4-18.5), kyphoscoliosis (n=4, 6.0% 95CI 1.7-14.6), hepatomegaly (n=4, 6.0% 95CI 1.7-14.6, 2 patients with hepato-renal polycystic disease, one hemochromatosis and one cirrhosis), right ventricle failure (n=2,3.0% 95CI 0.4-10.4), pericardial effusions (n=2,3.0% 95CI 0.4-10.4), right ventricle arrhythmogenic dysplasia (n=2,3.0% 95CI 0.4-10.4), diaphragmatic paralysis (n=1, 1.5% 95CI 0.1-8.0), carcinoid syndrome with tricuspid regurgitation (n=1, 1.5% 95CI 0.1-8.0), a right atrium pace-maker lead (n=1, 1.5% 95CI 0.1-8.0) and a takotsubo syndrome (n=1, 1.5% 95CI 0.1-8.0). Conclusion Aortic aneurysm and pneumonectomy are the most frequent and well known situation leading to a POS. Other causes less known were observed such as hepato-renal polycystic kidney, or atrial pacemaker probe that may be underdiagnosed in clinical practice.