Mepolizumab as a glucocorticoid-sparing agent in eosinophilic granulomatosis with polyangiitis (EGPA): is a lower dose sufficient?

INTRODUCTION: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of small-vessel vasculitis characterized by asthma, hyper-eosinophilia, and progressive multiorgan involvement. EGPA is traditionally treated using glucocorticoids, either alone or in combination with conventional immunosuppressants. Mepolizumab, a novel anti-interleukin (IL)-5 agent, has been approved as an add-on therapy for adult patients with EGPA. The recommended dose of mepolizumab is 300 mg (subcutaneous [SC]) every 4 weeks. CASE STUDY: The present report discusses three cases of refractory and/or relapsing EGPA in patients regularly taking a stable dose of prednisolone, all of whom were successfully treated with a lower-than-recommended dose of mepolizumab (100 mg SC, every 4 weeks). RESULTS: Treatment with a low dose of mepolizumab enabled us to gradually reduce glucocorticoid doses. In addition, patients treated with low doses of mepolizumab exhibited better asthma control and experienced sustained relapse-free periods. Responses to 100 mg of mepolizumab were comparable to those previously observed in patients taking the recommended dose of 300 mg. CONCLUSION: Our findings suggest that mepolizumab at a third of the recommended dose can achieve reasonable clinical efficacy in the long-term treatment of EGPA in some patients. Initiation of mepolizumab therapy in the early, eosinophilic phase of EGPA-which is characterized by asthma, marked blood eosinophilia, pulmonary infiltrates, and sinonasal abnormalities-may help to prevent the deleterious side-effects of long-term glucocorticoid use while reducing the cost of EGPA treatment.

Easy to Perform Physical Performance Tests to Identify COPD Patients with Low Physical Activity in Clinical Practice.

Background: The study investigates which physical performance or muscle function/mass tests significantly correlate with objectively measured physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD) and could potentially serve to identify physically inactive COPD patients in routine clinical practice. Methods: A cross-sectional, observational study was conducted in outpatients with moderate to very severe COPD. PA was measured during one week with the StepWatch Activity Monitor®, an ankle-worn accelerometer, and expressed in steps per day. Physical fitness and peripheral muscle function/mass were evaluated by the 4-meter gait speed (4MGS) test, the 6-minute walk distance (6MWD), the 30-second chair stand test (30sCST), the timed up and go test (TUGT), handgrip strength, arm muscle area, calf circumference, the fat-free mass index (FFMI), and ultrasound measurement of the quadriceps muscle. Spearman's rank correlation analysis and ROC analysis were performed. Results: The study population (N=111, 69% men, mean age 68 years) walked a mean of 8059 steps/day. The daily step count strongly correlated with the 6MWD (rho=0.684, p<0.001) and moderately with the 4MGS (rho=0.464, p<0.001), the TUGT (rho= -0.463, p<0.001), and the 30sCST (rho=0.402, p<0.001). The correlation with the FFMI was weak (rho=0.210, p=0.027), while the other parameters did not significantly correlate with the daily step count. The 6MWD had the best discriminative power to identify patients with very low PA defined as <5000 steps/day (AUC=0.802 [95% CI: 0.720-0.884], p<0.001), followed by the TUGT, the 4MGS, and the 30sCST. Conclusion: The 6MWD, the 4MGS, the TUGT, and the 30sCST are easy to perform in any clinical setting and may be used by clinicians in the screening of physically inactive COPD patients.

Nutritional Status of Patients with Chronic Obstructive Pulmonary Disease in Relation to their Physical Performance.

Nutritional abnormalities and physical inactivity are highly prevalent in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to determine the association between nutritional status/body composition and physical performance in patients with COPD. A cross-sectional observational study was conducted in outpatients with clinically stable, moderate to very severe COPD. In the assessment of nutritional status, we used dual energy X-ray absorptiometry, anthropometry, serum biomarkers, and the Mini-Nutritional Assessment (MNA) questionnaire. Physical performance was measured by the 6-minute walk distance (6MWD), 4-metre gait speed (4MGS), and physical activity. Univariate and multivariate analyses were performed. In 111 patients (mean age 68 years, 69% men), the mean 6MWD was 376 ± 119 m, 4MGS 0.9 ± 0.2 m/s, and the average daily step count 8,059 ± 4,757. Patients with low exercise capacity (6MWD ≤ 350 m) had a significantly lower lean mass index (LMI) (p < 0.01), fat-free mass index (FFMI) (p < 0.01), bone mineral content (p < 0.01), bone mineral density (p < 0.01), T-score (p < 0.05), MNA score (p < 0.01), and serum albumin and prealbumin levels (p < 0.05). Patients with low physical activity (daily step count ≤ median) had lower LMI, FFMI, MNA score, serum prealbumin (for all comparisons p < 0.05) and vitamin D levels (p < 0.01). However, none of the nutritional variables showed an independent association with low physical performance in the multivariate models. In conclusion, patients with low physical performance have deficient nutritional status, but we could not demonstrate an independent relationship between nutritional parameters and physical performance.

Chronic bronchial infection in COPD. Is there an infective phenotype?

Microorganisms, particularly bacteria, are frequently found in the lower airways of COPD patients, both in stable state and during exacerbations. The host-pathogen relationship in COPD is a complex, dynamic process characterised by frequent changes in pathogens, their strains and loads, and subsequent host immune responses. Exacerbations are detrimental events in the course of COPD and evidence suggests that 70% may be caused by microorganisms. When considering bacterial exacerbations, recent findings based on molecular typing have demonstrated that the acquisition of new strains of bacteria or antigenic changes in pre-existing strains are the most important triggers for exacerbation onset. Even in clinically stable COPD patients the presence of microorganisms in their lower airways may cause harmful effects and induce chronic low-grade airway inflammation leading to increased exacerbation frequency, an accelerated decline in lung function and impaired health-related quality of life. Besides intraluminal localisation in the distal airways, bacteria can be found in the bronchial walls and parenchymal lung tissue of COPD patients. Therefore, the isolation of pathogenic bacteria in stable COPD should be considered as a form of chronic infection rather than colonisation. This new approach may have important implications for the management of patients with COPD.

Predictors of adverse outcome in patients hospitalised for exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: It is crucial to identify risk factors for poor evolution of patients admitted to hospital with chronic obstructive pulmonary disease (COPD) in order to provide adequate intensive therapy and closer follow-up. OBJECTIVES: To identify predictors of adverse outcomes in patients hospitalised for exacerbation of COPD. METHODS: A prospective, observational study was conducted in patients admitted for exacerbation of COPD. Demographic and clinical parameters were evaluated, including different multidimensional prognostic scores. Adverse outcomes included the following: death during hospitalisation or 1-month follow-up, intensive care unit admission, invasive or non-invasive mechanical ventilation, prolonged hospitalisation (>11 days) and COPD-related emergency visit or readmission within 1 month after discharge. Univariate and multivariate analysis were performed. RESULTS: Of 155 patients included, an adverse outcome occurred in 69 (45%). Patients with an adverse outcome had lower forced expiratory volume in 1 s (p = 0.004) and more frequent exacerbations (p = 0.011), more frequently used oxygen at home (p = 0.042) and presented with lower pH (p < 0.001), lower ratio of arterial oxygen pressure to the fraction of inspired oxygen (p = 0.006), higher arterial carbon dioxide pressure (p < 0.001) and a worse score on several prognostic indices at admission. Independent predictors of adverse outcome were exacerbation of COPD in the previous year [odds ratio 3.9, 95% confidence interval (CI) 1.6-9.9; p = 0.004], hypercapnia (odds ratio 9.4, 95% CI 3.7-23.6; p < 0.001) and hypoxaemia (odds ratio 4.3, 95% CI 1.5-12.6; p = 0.008). In the presence of all three characteristics, the probability of an adverse outcome was 95%, while hypercapnia was the strongest prognostic factor with a risk of 54%. CONCLUSIONS: Patients with previous exacerbation of COPD, hypercapnia and hypoxaemia had the highest risk of an unfavourable evolution. The calculation of prognostic indices did not provide additional discriminative power.

[The treatment of asthma exacerbations in adults]. / Lijecenje egzacerbacija astme u odraslih.

Asthma exacerbation is characterized by a rapid and progressive worsening of symptoms, mainly dyspnea, cough, wheezing and chest tightness. The intensity of an exacerbation may vary form a mild, transient worsening marked by a cough and moderate shortness of breath to a very severe and life-threatening condition. The clinical features of asthma include increased rate of breathing, cough, and prolonged and difficult expiration. The expiratory flow limitation could be quantified, objectified, and monitored by the lung function measurements (PEF or FEV1 ). It is of crucial importance to recognize properly the early signs of an exacerbation, judge its severity, and promptly start the treatments. The strategy of the treatment of an asthma exacerbation includes the repeated administration of rapid-acting inhaled bronchodilators, the early introduction of systemic glucocorticoids and oxygen supplementation. The treatment is aimed to resolve the airflow limitation and ameliorate the hypoxemia, as quickly as possible. Mild exacerbations could be treated in general practice while the severe ones should be treated in emergence units.

Churg-Strauss syndrome with myopericardial involvement.

Churg-Strauss syndrome (CSS) is a small-vessel necrotizing vasculitis typically characterized by asthma, lung infiltrates, extravascular necrotizing granulomas and hypereosinophilia. Cardiac disease is a major contributor to disease-related death in CSS. We describe a 38-year-old man with late-onset asthma, allergic rhinosinusitis, and high extravascular and peripheral blood eosinophilia, who presented with migratory pulmonary infiltrates and acute myopericarditis. Antineutrophilic cytoplasmic antibodies (ANCA) were negative. Early therapy with medium-dose methylprednisolone led to resolution of the pericardial effusion and significant clinical improvement. In the present case report, the importance of early recognition of CSS in patients with asthma and peripheral eosinophilia is discussed. Cardiac magnetic resonance imaging, besides electro- and echocardiography, may be helpful in early detection of cardiac involvement in CSS, enabling appropriate treatment aimed to prevent further disease progression and potentially fatal consequences.

Efficacy and safety of Astragalus membranaceus in the treatment of patients with seasonal allergic rhinitis.

The study was designed to investigate efficacy and safety of Astragalus membranaceus (AM) in the treatment of patients with seasonal allergic rhinitis (SAR). AM is an active component in the herbal and mineral complex (HMC) registered in Croatia as a food supplement Lectranal. The study was designed as a 6-weeks, double-blind, placebo-controlled clinical trial and conducted in 48 adult patients with a moderate to severe SAR. The treatment efficacy was evaluated by the mean change in the symptom score (TSS), quality of life (QoL), specific serum IgE and IgG, nasal eosinophils, and physicians' and patients' global evaluation. Compared to placebo, HMC significantly decreased the intensity of rhinorrhea while for other primary efficacy variables the treatment groups did not differ. In contrast, investigators and patients equally judged the treatment with HMC as more efficacious. In addition, the analysis of changes from baseline inside the groups for TSS, QoL, and 4 main symptoms of SAR were strikingly in favor of the active treatment. In patients with SAR due to weed pollen allergy HMC significantly improved primary variables, reflective TSS and QoL. The study revealed a significant number of positive signals indicating the therapeutic effectiveness of the HMC in patients with SAR which should be further tested in larger, multicentre trials with more patients.