Combined vasomodulatory therapy for severe pulmonary hypertension in chronic hypersensitivity pneumonitis.

BACKGROUND: There are only a few reports of pulmonary hypertension (PH) in hypersensitivity pneumonitis (HP) and an approved vasomodulatory therapy for PH does not exist at all for interstitial lung disease (ILD), particularly for HP. CASE REPORT: The case of a 53-year-old woman with chronic HP and severe life-threatening PH treated with a combined specific vasomodulatory therapy is reported. Sustained clinical and hemodynamic improvement was achieved. CONCLUSIONS: Further investigation of PH in HP and specific vasomodulatory therapy is necessary.

[Chemotherapy in the Elderly with Non-Small Cell Lung Cancer: A Non-Interventional, Prospective, Multicentric Observational Study]. / Chemotherapie beim älteren Patienten mit nicht kleinzelligem Lungenkarzinom: Eine nicht-interventionelle, prospektive, multizentrische Beobachtungsstudie.

Background Elderly patients (70 years or older) with non-small cell lung cancer (NSCLC) do benefit from systemic chemotherapy as shown in many studies. We prospectively collected multicentric data on therapeutic decisions from patients 70 years or older to reflect the reality in the German health care system. Material and Methods Patients 70 years or older with NSCLC Stage IIIB or IV were eligible. No more than 20 consecutive patients from each center were included. Comorbidities, weighted by the Charlson-comorbidity-index, and survival data were collected. Results 253 patients were documented. Median age was 75.5 years (range 70 to 92) and 75 % were male. 2 % had no comorbidities, 5 % one, 15 % two, 24 % three and 55 % more than three. 237 patients (94 %) received systemic chemotherapy: 172 (73 %) as a combination and 58 (24 %) as monotherapy. Data from seven patients regarding therapy are missing. Combination regimens were in 66 % carboplatin- and in 30 % cisplatin-based. The most frequently given monotherapy was vinorelbin in 50 % of cases. In the group of the patients older than 80 years (n = 38), 53 % received mono therapy, 29 % a carboplatin-based regimen and 16 % no chemotherapy. Cisplatin was not administered in this age group. Median overall survival (OS) was 16.9 months. Patients with a Charlson-score ≤ 6 had 17.9 months, those > 6 12.0 months. With combination chemotherapy median OS was 23.5 months. Patients > 80 years had a median OS of 5.7 months. Conclusion A high percentage of patients older than 70 years received systemic therapy. Survival depended more on comorbidities than on age.

65Plus: open-label study of bevacizumab in combination with pemetrexed or pemetrexed/carboplatin as first-line treatment of patients with advanced or recurrent nonsquamous non-small-cell lung cancer.

BACKGROUND: The aim of the study was to investigate in terms of noninferiority the efficacy and safety of a monochemotherapy regimen of pemetrexed plus bevacizumab (BevPem) versus carboplatin/pemetrexed plus bevacizumab (BevCPem) in elderly patients as first-line treatment for advanced metastatic or recurrent nonsquamous non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: 65Plus was a Phase III, randomized, open-label study. In total, 253 patients received BevPem (n=119) or BevCPem (n=134). The primary outcome measure was progression-free survival. Secondary end points were overall survival, tumor response, and safety outcomes. Evaluations were performed for the whole study population and stratified according to Eastern Cooperative Oncology Group (ECOG) performance status (PS). RESULTS: Noninferiority of BevPem in comparison to BevCPem could not be demonstrated for the overall population (P=0.7864). Significant superiority of the combined treatment BevCPem was seen in patients of ECOG PS 0-1 (median PFS 5.1 vs 6.9 months, HR 1.353, 95% CI 1.03-1.777), while the opposite tendency was observed in patients with ECOG PS 2 (median PFS 2.9 vs 1.5 months, HR 0.628, 95% CI 0.195-2.025). Overall, better tolerability was found for the BevPem group, irrespective of ECOG PS. CONCLUSION: Results from the 65plus study give evidence that BevPem and BevCPem treatments may exert differential effects on PFS, depending on the patients ECOG PS. It appears that patients with better ECOG PS (0-1) benefited more from the combined treatment with carboplatin, while the group comprising more severely impaired patients (ECOG PS 2) benefited more from the monochemotherapy.

Portopulmonary hypertension.

Portopulmonary hypertension (PPHT) is defined as precapillary pulmonary hypertension accompanied by hepatic disease or portal hypertension. Pulmonary hypertension results from excessive pulmonary vascular remodeling and vasoconstriction. These histological alterations have been indistinguishable from those of other forms of pulmonary arterial hypertension. Factors involved in the pathogenesis of PPHT include volume overload, hyperdynamic circulation, and circulating vasoactive mediators. The disorder has a substantial impact on survival and requires focused treatment. Liver transplantation in patients with moderate to severe PPHT is associated with a significantly reduced survival rate. The best medical treatment for patients with PPHT is controversial; most authors currently regard continuous intravenous application of prostacyclin as the treatment of choice for patients with severe PPHT. There is only very limited reported experience with inhaled prostacyclin or its analog, iloprost. Increasing evidence of the efficacy of the endothelin-receptor antagonist bosentan and of the phosphodiesterase-5 inhibitor sildenafil is emerging in highly selected patients with PPHT. In the future, a combination therapy of the above-mentioned agents might become a therapeutic option. Other agents such as beta-blockers seem to be harmful to patients with moderate to severe portopulmonary hypertension. Up-to-date, randomized, double-blind, controlled clinical trials are lacking and are needed urgently.

Successful switch from long-term intravenous iloprost to non-invasive combination therapy in idiopathic pulmonary arterial hypertension.

In Europe intravenous (IV) iloprost, an alternative to epoprostenol, is an accepted treatment option for severely compromised patients with idiopathic pulmonary arterial hypertension (IPAH). Once initiated, this therapy usually has to be continued lifelong or as bridging to transplantation. In our paper we describe two patients with IPAH in World Health Organisation (WHO) functional classes II and III while on treatment with continuous IV iloprost monotherapy or combination therapy with continuous IV iloprost plus oral bosentan, respectively. The duration of IV iloprost therapy was 4.5 and 2.5 years, respectively. Because of life-threatening or recurring catheter-related complications during long-term IV iloprost therapy, these patients were switched to non-invasive combination therapy consisting of oral bosentan plus aerosolized iloprost (patient 1) and oral bosentan plus aerosolized iloprost plus oral sildenafil (patient 2), respectively. After four weeks of additional bosentan therapy, stepwise reduction and discontinuation of IV iloprost were performed within eight hours in the patient in WHO class II, and within five days in the patient in WHO class III. Simultaneously, therapy with aerosolized iloprost was started in the first patient and with aerosolized iloprost plus sildenafil in the second patient. Both patients were safely switched from IV iloprost to non-invasive combination therapy while WHO classification of functional status remained unchanged for at least 12 and 14 months, respectively. These data suggest that selected patients with complications due to IV iloprost treatment can be safely switched to non-IV combination therapies.

Outcome and prognostic features of intensive care unit treatment in patients with hematological malignancies.

OBJECTIVE: To assess the outcome of intensive care unit (ICU) treatment in patients with hematological malignancies. DESIGN AND SETTING: Retrospective cohort study in the medical ICU of a university hospital. PATIENTS: 104 critically ill patients after receiving conventional chemotherapy or autologous hematopoietic stem cell transplantation. INTERVENTIONS: We analyzed demographic data, underlying disease, intensity of antineoplastic regimen, cause of admission, need for mechanical ventilation, and hemofiltration, ICU survival, and survival after discharge, furthermore neutrophil count, C-reactive protein (150 mg/l), antithrombin III, prothrombin time, and SAPS II (50) at ICU admission. All recorded variables were evaluated for prognostic relevance by univariate and multivariate analyses. MEASUREMENTS AND RESULTS: Overall ICU mortality was 44%, with significantly higher mortality in ventilated patients (74% vs. 12% in nonventilated patients, p<0.001). Overall survival for the entire group 6 months and 1 year after ICU admission was 33% and 29%, respectively. Multivariate analysis revealed mechanical ventilation and SAPS II as independent prognostic factors of both ICU mortality and long-term survival, while C-reactive protein predicted only ICU mortality. CONCLUSIONS: The outcome of patients not requiring ventilatory support in this study was encouraging, while invasive ventilation was again confirmed as predicting a dismal prognosis in this population. Efforts should be directed to avoiding this procedure by reducing the pulmonary toxicity of antineoplastic treatment and to making ventilatory support more tolerable.

Haemoptysis due to pulmonary venous stenosis.

Haemoptysis is a potentially life-threatening condition with the need for prompt diagnosis. In about 10-20% of all cases the bleeding source remains unexplained with the standard diagnostic approach. The aim of this article is to show the necessity of widening the diagnostic approach to haemoptysis with consideration of pulmonary venous stenosis as a possible cause of even severe haemoptysis and haemoptoe. A review of the literature was performed using the Medline/PubMed database with the terms: "pulmonary venous stenosis", "pulmonary venous infarction" and "haemoptysis". Further references from the case reports were considered. 58 case reports and case collections about patients with haemoptysis due to pulmonary venous stenosis were detected. This review gives an overview about the case reports and discusses the underlying pathophysiology and the pros and cons of different imaging techniques for the detection of pulmonary venous stenosis. Several conditions predispose to the obstruction of the mediastinal pulmonary veins. Clinical findings are unspecific and may be misleading. Pulmonary venous stenosis can be detected using several imaging techniques, yet three-dimensional magnetic resonance-angiography and three-dimensional contrast-enhanced computed tomography are the most appropriate. Pulmonary venous stenosis should be considered in patients with haemoptysis.

Combination therapy for portopulmonary hypertension with intravenous iloprost and oral bosentan.

Severe portopulmonary hypertension (PPHTN) is a rare complication of liver cirrhosis and carries a poor prognosis. In the last years, intravenous (IV) epoprostenol has been suggested to be the optimal medical treatment for PPHTN, and recently oral bosentan has been shown to be efficacious and safe in selected patients with PPHTN. We report a case of PPHTN suffering from recurrent right heart failure while on treatment with IV iloprost, which was successfully managed by combination therapy with IV iloprost plus oral bosentan, providing sustained cardiopulmonary stabilization for at least two years. This report documents the first case of a patient with PPHTN successfully treated with the combination of IV iloprost and oral bosentan over an extended period. Thus, combination therapy with IV iloprost and oral bosentan might be a promising new option for selected patients suffering from PPHTN and recurrent right heart failure.