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.

A French multicentric study and review of pulmonary Nocardia spp. in cystic fibrosis patients.

Some bacterial species recovered from the airways of cystic fibrosis (CF) patients are indisputably associated with lung infections, whereas the clinical relevance of others, such as Nocardia spp., remains unclear. Sixteen French CF cases of colonization/infection with Nocardia spp. were reviewed in order to evaluate the epidemiology, the clinical impact and the potential treatment of these bacteria, and results were compared to those of the literature. Five Nocardia species were identified, Nocardia cyriacigeorgica being the major species (50 % of cases). At first isolation, Nocardia was the sole pathogen recovered in six patients. Seven patients presented pulmonary exacerbation. For 12 patients, antimicrobial treatment against Nocardia was started immediately, mainly based on cotrimoxazole (6 of the 12 cases). In this study, we highlight the heterogeneity of the clinical management of Nocardia spp. in CF. Guidelines for the clinical management of Nocardia infections in CF patients are proposed.

Granulomatous disease in CVID: retrospective analysis of clinical characteristics and treatment efficacy in a cohort of 59 patients.

BACKGROUND: Granulomatous disease (GD) will develop in a subset of patients with common variable immunodeficiency (CVID). Little is known about the efficacy of therapeutic agents used for treating this disorder. OBJECTIVE: To evaluate the efficacy of immunosuppressive drugs with the help of a set of clinical, biological and radiological criteria. METHOD: Clinical and laboratory features of CVID patients were collected from the French DEFI cohort, a prospective study on adults with hypogammaglobulinemia. The medical charts of 55 patients (93 %) of the GD cohort were reviewed. RESULTS: Among 436 subjects with CVID, 59 patients (13.5 %) were diagnosed with GD. Of the 55 patients in whom medical charts were available, 32 patients received treatment for the granulomatous disease. Corticosteroids were the most frequently used drug. Complete response to treatment was infrequent. It was achieved with corticosteroids, cyclophosphamide, hydroxychloroquine, rituximab and methotrexate. Azathioprine, cyclosporine, mycophenolate mofetil, sirolimus, infliximab and thalidomide led to partial or absence of response. Complete and partial responses were observed in lymph nodes, lungs, liver, skin, bone marrow and central nervous system. Absent of response for gastrointestinal tract granulomas was noted in all cases of treatment attempt. CONCLUSION: CVID patients with GD exhibit a particular biological phenotype. Treatment should be considered in any symptomatic patient or if there is evidence of organ dysfunction. Corticosteroids are the drug of choice in most instances but response to treatment is often unsatisfactory.

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.

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 FEV(1) 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 FEV(1) 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.

Prophylaxis of invasive aspergillosis with voriconazole or caspofungin during building work in patients with acute leukemia.

BACKGROUND: Invasive aspergillosis is a common life-threatening infection in patients with acute leukemia. The presence of building work near to hospital wards in which these patients are cared for is an important risk factor for the development of invasive aspergillosis. This study assessed the impact of voriconazole or caspofungin prophylaxis in patients undergoing induction chemotherapy for acute leukemia in a hematology unit exposed to building work. DESIGN AND METHODS: This retrospective cohort study was carried out between June 2003 and January 2006 during which building work exposed patients to a persistently increased risk of invasive aspergillosis. This study compared the cumulative incidence of invasive aspergillosis in patients who did or did not receive primary antifungal prophylaxis. The diagnosis of invasive aspergillosis was based on the European Organization for Research and Treatment of Cancer/Mycosis Study Group criteria. RESULTS: Two-hundred and fifty-seven patients (213 with acute myeloid leukemia, 44 with acute lymphocytic leukemia) were included. The mean age of the patients was 54 years and the mean duration of their neutropenia was 21 days. Eighty-eight received antifungal prophylaxis, most with voriconazole (n=74). The characteristics of the patients who did or did not receive prophylaxis were similar except that pulmonary antecedents (chronic bronchopulmonary disorders or active tobacco use) were more frequent in the prophylaxis group. Invasive aspergillosis was diagnosed in 21 patients (12%) in the non-prophylaxis group and four (4.5%) in the prophylaxis group (P=0.04). Pulmonary antecedents, neutropenia at diagnosis and acute myeloid leukemia with high-risk cytogenetics were positively correlated with invasive aspergillosis, whereas primary prophylaxis was negatively correlated. Survival was similar in both groups. No case of zygomycosis was observed. The 3-month mortality rate was 28% in patients with invasive aspergillosis. CONCLUSIONS: This study suggests that antifungal prophylaxis with voriconazole could be useful in acute leukemia patients undergoing first remission-induction chemotherapy in settings in which there is a high-risk of invasive aspergillosis.

Cardiac MRI in pulmonary artery hypertension: correlations between morphological and functional parameters and invasive measurements.

OBJECTIVE: To compare cardiac MRI with right heart catheterisation in patients with pulmonary hypertension (PH) and to evaluate its ability to assess PH severity. MATERIALS AND METHODS: Forty patients were included. MRI included cine and phase-contrast sequences, study of ventricular function, cardiac cavity areas and ratios, position of the interventricular septum (IVS) in systole and diastole, and flow measurements. We defined four groups according to the severity of PH and three groups according to IVS position: A, normal position; B, abnormal in diastole; C, abnormal in diastole and systole. RESULTS: IVS position was correlated with pulmonary artery pressures and PVR (pulmonary vascular resistance). Median pulmonary artery pressures and resistance were significantly higher in patients with an abnormal septal position compared with those with a normal position. Correlations were good between the right ventricular ejection fraction and PVR, right ventricular end-systolic volume and PAP, percentage of right ventricular area change and PVR, and diastolic and systolic ventricular area ratio and PVR. These parameters were significantly associated with PH severity. CONCLUSION: Cardiac MRI can help to assess the severity of PH.

New echocardiographic prognostic factors for mortality in pulmonary arterial hypertension.

AIMS: The present role of echocardiography is generally restricted to screening for pulmonary arterial hypertension (PAH). The aim of our study was to identify new echocardiographic prognostic factors for mortality in PAH which would give this imaging modality a genuine role in patient management. METHODS AND RESULTS: At inclusion, all patients underwent right cardiac catheterization and echocardiography. Seventy-nine patients were followed for a median of 12 months, of whom 16 died of their pulmonary disease. We identified seven echocardiographic parameters that were associated with mortality, four of which have not previously been described in the literature: mean pulmonary artery pressure (PAP) >or=49 mmHg (P = 0.012), dPAP >or= 29 mmHg (P = 0.006), abnormal end-diastolic septal curve (P = 0.027), and inferior vena cava diameter >or=20 mm with respiratory variation of diameter <50% (P = 0.018). These parameters remained significant after adjustment for NYHA class and 6 min walk test distance. CONCLUSION: Echocardiography should take an important place in the management of PAH and should not be restricted merely to screening for the disease.

Late-onset combined immune deficiency: a subset of common variable immunodeficiency with severe T cell defect.

BACKGROUND: Common variable immunodeficiency (CVID) is a primary immune deficiency defined by defective antibody production. In most series, a small proportion of patients present with opportunistic infections (OIs). METHODS: The French DEFI study has enrolled patients with primary hypogammaglobulinemia and allows a detailed clinical and immunologic description of patients with previous OIs and/or at risk for OIs. RESULTS: Among 313 patients with CVID, 28 patients (8.9%) presented with late-onset combined immune deficiency (LOCID), defined by the occurrence of an OI and/or a CD4(+) T cell count <200 x 10(6) cells/L, and were compared with the remaining 285 patients with CVID. The patients with LOCID more frequently belonged to consanguineous families (29% vs 8%; P = .004). They differed from patients with CVID with a higher prevalence of splenomegaly (64% vs 31%), granuloma (43% vs 10%), gastrointestinal disease (75% vs 42%), and lymphoma (29% vs 4%). Even on immunoglobulin substitution, they required more frequent antibiotics administration and hospitalization. Lymphocyte counts were lower, with a marked decrease in CD4(+) T cell counts (158 x 10(6) vs 604 x 10(6) cells/L; P < .001) and a severe defect in naive CD45RA(+)CCR7(+)CD4(+) T cell counts (<20% of total CD4(+) T cells in 71% of patients with LOCID vs 37% of patients with CVID; P = .001). The CD19(+) B cell compartment was also significantly decreased (20 x 10(6) vs 102 x 10(6) cells/L; P < .001). CONCLUSIONS: LOCID differs from classic CVID in its clinical and immunologic characteristics. Systematic T cell phenotype may help to discriminate such patients from those with CVID. Identification of this phenotype should result in a more fitted diagnostic and therapeutic approach of infections and could provide insights for genetic diagnosis.

The Use of Transthoracic Echocardiogram to Quantify Pulmonary Vascular Resistance in Patients with Systemic Sclerosis.

OBJECTIVE: To explore the accuracy of tricuspid regurgitation velocity (TRV) to right ventricular outflow tract time-velocity integral (TVIRVOT) ratio by Doppler to determine pulmonary vascular resistance (PVR) in patients with systemic sclerosis (SSc). METHODS: Thirty-five consecutive adult patients with SSc, fulfilling the 2013 European League Against Rheumatism/American College of Rheumatology classification criteria, with sinus rhythm referred for right heart catheterization (RHC), were retrospectively included. All patients underwent a transthoracic echocardiogram (TTE) performed within 24 h of RHC. Patients with SSc were recruited regardless of disease activity, cardiac symptoms, and treatment regimen. Doppler measurements were compared to RHC measurements. A linear regression equation was generated to predict PVR by echocardiogram based on the TRV/TVIRVOT ratio. The accuracy of Doppler measurements for predicting PVR > 3 Wood units was assessed by computing the areas under the receiver-operating characteristic curves. RESULTS: There were 20 (57%) females in the study. The mean age was 65 ± 12 years. Mean and systolic pulmonary arterial pressures were 31 ± 8 and 53 ± 15 mmHg, respectively. There was a good correlation between TRV/TVIRVOT ratio assessed by Doppler and PVR measured by RHC (R = 0.743, p < 0.001). The equation generated by this analysis was the following: PVR by Doppler = 11.3 × (TRV/TVIRVOT) + 1.7. A cutoff value of 0.21 for TRV/TVIRVOT ratio provided the best sensitivity (86%) and specificity (86%) to determine PVR > 3 Wood units. CONCLUSION: Our study suggests that TTE using Doppler could be a useful and noninvasive tool for estimating PVR in patients with SSc.

Adenoid cystic carcinoma of the lung: interest of 18FDG PET/CT in the management of an atypical presentation.

Adenoid cystic carcinoma (ACC) is a common head and neck tumor originating from salivary glands but that can also exceptionally develop in the trachea and major bronchi. ACC is generally considered as a slow-growing, low-grade malignancy with prolonged clinical course. Metastases are very unusual and recurrences are more often local. Treatment for localized ACC is surgery. We here report for the first time a case of lung ACC with a synchronous liver metastasis proved by biopsy. Moreover, we report the interest of performing a 18FDG PET-CT as both primary tumor and liver metastasis presented an intense FDG uptake. The specificity of the liver 18FDG uptake was confirmed by Glut-1 positive immunostaining. We propose that 18FDG PET-CT should be considered in the initial staging of lung ACC in selected patients.

[Allergic disease treatments: classic and innovative therapeutics]. / Traitements des maladies allerqiques : thérapeutiques classiques et nouvelles.

The purpose of this article is to focus on anti-allergic therapies that directly target cellular or humoral actors of the allergic reaction and which are quasi-exclusively dedicated to the treatment of allergic diseases. This leads to successively look at: anti-histamines, classic treatments but in constant improvement, allergen immunotherapy which is experiencing a second life with the validation of the sublingual route and monoclonal anti-IgE antibody, a real new therapeutic class which has demonstrated his efficacy in patients with severe non-controlled allergic asthma.

[Therapeutic management of asthma]. / Stratégie thérapeutique dans la prise en charge de lásthme.

Therapeutic management of asthma is based on the key role of lower airway inflammation. New treatments and inhalation devices in conjunction with international recommendations have contributed to improve asthma management. The aim of asthma treatment is to avoid acute asthma and to reduce or suppress symptoms, to permit normal life (familial, scholar or professional) and to normalize lung function. The final goal is to improve patient quality of life and must also integrate the benefice/risk ratio of treatment. Asthmatic patients need to be regularly followed by a physician. Recently, French Anaes recommendations suggested to base the medical follow up on asthma control checking. Beside treatment of chronic asthma, acute asthma remains a potential emergency that needs to be rapidly identified and treated, following strict rules of clinical management.

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.

Lethal hemorrhagic alveolitis after adenovirus pneumonia in a lung transplant recipient.

Viral infections are frequent and severe in lung transplant recipients. They frequently occur during the first year after transplantation. We report on a rare case of bilateral adenovirus necrotizing pneumonia with a diffuse alveolar hemorrhage, 4 years after bilateral lung transplantation. The medical evolution was lethal in 72 hours because of respiratory, renal, and cardiac failure. Considering this case and the growing evidence on the severity of adenoviral infections, we call for controlled studies and therapeutic recommendations.