Bacterial lysate add-on therapy to reduce exacerbations in severe asthma: A double-blind placebo-controlled trial.

BACKGROUND: Asthma exacerbations are frequently induced by respiratory tract infections (RTIs). Bacterial lysates have been described to possess immune-modulatory effects and reduce RTIs as well as asthma symptoms in children. However, whether bacterial lysates have similar effects in adult asthma patients is unknown. AIMS: To reduce asthma exacerbations by add-on bacterial lysate therapy in adults with severe asthma and to characterize the clinical and immune-modulatory effects of this treatment. METHODS: Asthma patients (GINA 4) with ≥2 annual exacerbations in the previous year were included. The intervention regimen consisted of OM-85/placebo for 10 consecutive days per month for 6 months during two winter seasons. Primary end-point was the number of severe asthma exacerbations within 18 months. The study was approved by the national and local ethical review board and registered in the Dutch Trial Registry (NL5752). All participants provided written informed consent. RESULTS: Seventy-five participants were included (38 OM-85; 37 placebo). Exacerbation frequencies were not different between the groups after 18 months (incidence rate ratio 1.07, 95%CI [0.68-1.69], p = 0.77). With the use of OM-85, FEV1% increased by 3.81% (p = 0.04) compared with placebo. Nasopharyngeal swabs taken during RTIs detected a virus less frequently in patients using OM-85 compared to placebo (30.5% vs. 48.0%, p = 0.02). In subjects with type 2 inflammation adherent to the protocol (22 OM-85; 20 placebo), a non-statistically significant decrease in exacerbations in the OM-85 group was observed (IRR = 0.71, 95%CI [0.39-1.26], p = 0.25). Immune-modulatory effects included an increase in several plasma cytokines in the OM-85 group, especially IL-10 and interferons. Peripheral blood T- and B cell subtyping, including regulatory T cells, did not show differences between the groups. CONCLUSION: Although OM-85 may have immune-modulatory effects, it did not reduce asthma exacerbations in this heterogeneous severe adult asthma group. Post hoc analysis showed a potential clinical benefit in patients with type 2 inflammation.

Decreased physical activity in adults with bronchial asthma.

Contradictory findings have been reported in the literature on the impact that bronchial asthma may have on habitual physical activity. The present study was designed to compare physical activity, objectively measured with an activity monitor, between adults with bronchial asthma and apparently healthy controls. Valid registrations of physical activity were obtained in 226 patients with asthma and 201 healthy controls. A multiple general linear model was used to test between group differences and to correct for confounding of the results due to between group differences in BMI and employment status. In the patients, statistically significantly lower values were found for average steps/day (-1202; CI -1893 to -511; P = 0.001), physical activity level based on an estimate of a person's total energy expenditure (-0.035; CI -0.067 to -0.003); P = 0.034) and daily time (minutes) spent at vigorous intensive physical activity (-11; CI -17 to -1; P < 0.001). In addition, weak albeit significant correlations were found between measures of physical activity and asthma control. We conclude that bronchial asthma in adults is associated with a significant reduction in physical activity as compared to apparently healthy controls and is accompanied by a lower perceived health status. This is in support of the postulation of PA as potential pathway to better the outcome of care for these patients.

Development of an integral assessment approach of health status in patients with obstructive airway diseases: the CORONA study.

BACKGROUND: Traditional assessment of patients with obstructive lung diseases (asthma and chronic obstructive pulmonary disease; COPD) relies on physiological tests. The COPD and Asthma Rotterdam Integrated Care Approach (CORONA) study aims to develop a diagnostic pathway with a more comprehensive approach to the assessment of patients with asthma and COPD in secondary care. METHODS: An eight-step method was used to develop and implement the pathway for patients with asthma or COPD referred to an outpatient hospital setting. RESULTS: The diagnostic pathway consists of an evidence-based set of measurements prioritized by a Delphi procedure. The pathway incorporates three innovative diagnostics: the metronome-paced hyperventilation test to measure dynamic hyperinflation, an activity monitor to objectively evaluate physical activity in daily life, and the Nijmegen Clinical Screening Instrument as a comprehensive assessment tool to acquire detailed insight into symptoms, functional limitations, and quality of life. CONCLUSION: An innovative diagnostic pathway was developed and implemented for patients with obstructive lung diseases referred to secondary care. As this pathway aims to provide a comprehensive analysis of health status, it focuses on biomedical aspects and also reviews behavioral aspects that further elucidate the patient's health status. The added value of the diagnostic pathway needs to be determined from both an organizational perspective and from the individual patient's viewpoint.