Kathrin M. Stoiber

Effectiveness of omalizumab in patients 50 years and older with severe persistent allergic asthma

BACKGROUND Omalizumab is approved for the treatment of severe allergic asthma. OBJECTIVES To compare the efficacy of omalizumab therapy in patients 50 years or older with patients younger than 50 years. METHODS Between November 2005 and November 2007 a total of 174 asthma patients 50 years or older (40.7% male, 51.1% taking oral corticosteroids, and mean [SD] serum IgE level of 315 [353] U/L) and 297 asthma patients younger than 50 years (40.0% male, 50.5% taking oral corticosteroids, and mean [SD] serum IgE level of 363 [431] U/L) who met the European Union criteria for add-on therapy with anti-IgE were treated prospectively with omalizumab for 4 months as part of 2 postmarketing surveillance trials. RESULTS Compared with the pretrial period omalizumab treatment reduced the rate of severe exacerbations in patients 50 years or older by 68.9% (P < .001) and in patients younger than 50 years by 75.4% (P < .001). After 4 months there was a marked reduction of daily asthma symptoms and nocturnal awakenings by 67.8% and 72.6% in the older and by 79.3% and 82.5% in the younger patients, respectively (P < .001, all 4 comparisons). In 60% of patients 50 years or older lung function improved compared with 69% of patients younger than 50 years. Efficacy of omalizumab was rated as excellent or good by most physicians in patients 50 years or older (68.4%) and younger than 50 years (76.8%, P = .05 elderly vs younger). Adverse events were reported in 35.5% of patients 50 years or older and 32.1% of patients younger than 50 years. There was a higher rate of discontinuation of omalizumab therapy in older patients (20.9% vs 11.1%, P = .006). CONCLUSIONS The present study confirms the clinical efficacy of omalizumab in patients with severe allergic asthma irrespective of age in a real-life setting outside the omalizumab trial program.

Omalizumab in patients with severe asthma: the XCLUSIVE study.

Background and Aims:  Although the efficacy and safety of omalizumab (OMA) in uncontrolled severe allergic asthma has been demonstrated in several randomised controlled trials (RCTs), information on the treatment in a practice‐related setting is limited. Thus, the purpose of this prospective multi‐centre study (XCLUSIVE) was to investigate the efficacy, compliance and utilisation of OMA therapy in real‐life clinical practice in Germany.

Circulating biomarkers of tissue remodelling in pulmonary hypertension.

Objective: Besides persisting high pulmonary arterial pressure and increased pulmonary vascular resistance, remodelling of pulmonary tissues and subsequently the right heart are the key pathomechanisms of pulmonary hypertension (PH). Extracellular matrix maintenance in this context plays a central role. Methods: We tested the hypothesis that plasma concentration of matrix metalloproteinase (MMP)-2, tissue inhibitor of matrix metalloproteinases (TIMP)-4 and tenascin C (TNC) might be useful as biomarkers for assessing the severity of PH. Therefore, the concentrations of MMP-2, TIMP-4, TNC and N-terminal b-type natriuretic peptide (NT-proBNP) of 36 PH patients were compared with those of 44 age- and gender-matched healthy volunteers. Additionally, lung function, 6-min walk distance and right heart function were assessed. Results: In PH patients, significantly elevated plasma levels of MMP-2, TIMP-4, TNC and NT-proBNP were detected. In particular, TIMP-4 was significantly increased in patients with higher NYHA classification, and in patients with severe right ventricular hypertrophy. Conclusion: Monitoring of plasma TIMP-4 and to a lesser extent of MMP-2 and TNC levels in PH patients might help to assess the beneficial effects of PH pharmacotherapy on tissue remodelling.

Isolated IgG4-related interstitial lung disease: unusual histological and radiological features of a pathologically proven case

IgG4-related lung disease is commonly associated with autoimmune pancreatitis. Recently, isolated IgG4-related interstitial lung disease (ILD) without other organ involvement has newly been reported in two cases with clinical features of nonspecific interstitial pneumonitis (NSIP).We report the first case of an isolated IgG4-related ILD in a 78-year-old man with dry cough and dyspnea, whose clinical findings proved to be different from NSIP. Serum IgG4 levels were increased. Chest CT scan revealed bilateral consolidations especially in the lower lobes, enlarged mediastinal and hilar lymph nodes and pleural effusions. Video-assisted thoracoscopic (VATS) lung biopsy revealed a pattern similar to usual interstitial pneumonia (UIP) and an abundant IgG4-positive plasma cell infiltration. He was effectively treated by steroid therapy.Increasing recognition of IgG4 related diseases has led to a growing number of new entities. The novel concept of isolated IgG4-related ILD as a pulmonary manifestation of a systemic IgG4-related disorder should be taken into account as a possible differential diagnosis of ILD and mass-forming lesions, even when no other organ manifestation is clinically apparent at the time of diagnosis. Lung specific diagnostic criteria and algorithms are required to enhance diagnostic accuracy in cases of possible IgG4-related ILD.

Effects of Nasal Positive Expiratory Pressure on Dynamic Hyperinflation and 6-Minute Walk Test in Patients With COPD

INTRODUCTION: Dynamic hyperinflation is an important target in the treatment of COPD. There is increasing evidence that positive expiratory pressure (PEP) could reduce dynamic hyperinflation during exercise. PEP application through a nasal mask and a flow resistance device might have the potential to be used during daily physical activities as an auxiliary strategy of ventilatory assistance. The aim of this study was to determine the effects of nasal PEP on lung volumes during physical exercise in patients with COPD. METHODS: Twenty subjects (mean ± SD age 69.4 ± 6.4 years) with stable mild-to-severe COPD were randomized to undergo physical exercise with nasal PEP breathing, followed by physical exercise with habitual breathing, or vice versa. Physical exercise was induced by a standard 6-min walk test (6MWT) protocol. PEP was applied by means of a silicone nasal mask loaded with a fixed-orifice flow resistor. Body plethysmography was performed immediately pre-exercise and post-exercise. RESULTS: Differences in mean pre- to post-exercise changes in total lung capacity (−0.63 ± 0.80 L, P = .002), functional residual capacity (−0.48 ± 0.86 L, P = .021), residual volume (−0.56 ± 0.75 L, P = .004), SpO2 (−1.7 ± 3.4%, P = .041), and 6MWT distance (−30.8 ± 30.0 m, P = .001) were statistically significant between the experimental and the control interventions. CONCLUSIONS: The use of flow-dependent expiratory pressure, applied with a nasal mask and a PEP device, might promote significant reduction of dynamic hyperinflation during walking exercise. Further studies are warranted addressing improvements in endurance performance under regular application of nasal PEP during physical activities.

Pulmonary pulse transit time: a novel echocardiographic indicator of hemodynamic and vascular alterations in pulmonary hypertension and pulmonary fibrosis.

Pulse transit time (PTT) is generally assumed to be a surrogate marker for blood pressure changes and arterial stiffness. The aim was to evaluate whether pulmonary PTT (pPTT) may be noninvasively measured by Doppler echocardiography and whether it might be valuable for detecting pulmonary hemodynamic and vascular alterations.

Relation of Exercise Capacity With Lung Volumes Before and After 6-Minute Walk Test in Subjects With COPD

INTRODUCTION: There is growing evidence that exercise-induced variation in lung volumes is an important source of ventilatory limitation and is linked to exercise intolerance in COPD. The aim of this study was to compare the correlations of walk distance and lung volumes measured before and after a 6-min walk test (6MWT) in subjects with COPD. METHODS: Forty-five subjects with stable COPD (mean pre-bronchodilator FEV1: 47 ± 18% predicted) underwent a 6MWT. Body plethysmography was performed immediately pre- and post-6MWT. RESULTS: Correlations were generally stronger between 6-min walk distance and post-6MWT lung volumes than between 6-min walk distance and pre-6MWT lung volumes, except for FEV1. These differences in Pearson correlation coefficients were significant for residual volume expressed as percent of total lung capacity (−0.67 vs −0.58, P = .043), percent of predicted residual volume expressed as percent of total lung capacity (−0.68 vs −0.59, P = .026), inspiratory vital capacity (0.65 vs 0.54, P = .019), percent of predicted inspiratory vital capacity (0.49 vs 0.38, P = .037), and percent of predicted functional residual capacity (−0.62 vs −0.47, P = .023). CONCLUSIONS: In subjects with stable COPD, lung volumes measured immediately after 6MWT are more closely related to exercise limitation than baseline lung volumes measured before 6MWT, except for FEV1. Therefore, pulmonary function testing immediately after exercise should be included in future studies on COPD for the assessment of exercise-induced ventilatory constraints to physical performance that cannot be adequately assessed from baseline pulmonary function testing at rest.