Gert-Jan Braunstahl

Mucosal and systemic inflammatory changes in allergic rhinitis and asthma: a comparison between upper and lower airways

Background Local airway inflammation and airway remodelling are considered important in the clinical expression of allergic asthma.

The eXpeRience registry: The ‘real-world’ effectiveness of omalizumab in allergic asthma

Omalizumab has demonstrated therapeutic benefits in controlled clinical trials. Evaluation of outcomes in real-world clinical practice is needed to provide a complete understanding of the benefits of omalizumab treatment. eXpeRience was a 2-year, international, single-arm, open-label, observational registry that evaluated real-world effectiveness, safety and use of omalizumab therapy in 943 patients with uncontrolled persistent allergic asthma. Effectiveness variables (physicians Global Evaluation of Treatment Effectiveness [GETE], and change from baseline in exacerbation rate, symptoms, rescue medication use, and oral corticosteroid [OCS] use) were evaluated at pre-specified time-points. Safety data were also recorded. By physicians GETE, 69.9% of patients were responders to omalizumab after 16 (±1) weeks. The proportion of patients with no clinically significant exacerbations increased from 6.8% during the 12-month pre-treatment period to 54.1% and 67.3% at Months 12 and 24, respectively. Symptoms and rescue medication use at Month 24 were reduced by >50% from baseline. Maintenance OCS use was lower at Month 24 (14.2%) compared with Month 12 (16.1%) and baseline (28.6%). Overall, omalizumab had an acceptable safety profile. The results from eXpeRience indicate that omalizumab was associated with improvements in outcomes in patients with uncontrolled persistent allergic asthma; these improvements were consistent with the results of clinical trials.

Systemic Inflammation and Lung Function Impairment in Morbidly Obese Subjects with the Metabolic Syndrome

Background. Obesity and asthma are associated. There is a relationship between lung function impairment and the metabolic syndrome. Whether this relationship also exists in the morbidly obese patients is still unknown. Hypothesis. Low-grade systemic inflammation associated with the metabolic syndrome causes inflammation in the lungs and, hence, lung function impairment. Methods. This is cross-sectional study of morbidly obese patients undergoing preoperative screening for bariatric surgery. Metabolic syndrome was assessed according to the revised NCEP-ATP III criteria. Results. A total of 452 patients were included. Patients with the metabolic syndrome (n = 293) had significantly higher blood monocyte (mean 5.3 versus 4.9, P = 0.044) and eosinophil percentages (median 1.0 versus 0.8, P = 0.002), while the total leukocyte count did not differ between the groups. The FEV1/FVC ratio was significantly lower in patients with the metabolic syndrome (76.7% versus 78.2%, P = 0.032). Blood eosinophils were associated with FEV1/FVC ratio (adj. B −0.113, P = 0.018). Conclusion. Although the difference in FEV1/FVC ratio between the groups is relatively small, in this cross-sectional study, and its clinical relevance may be limited, these data indicate that the presence of the metabolic syndrome may influence lung function impairment, through the induction of relative eosinophilia.

Effect of bariatric surgery on asthma control, lung function and bronchial and systemic inflammation in morbidly obese subjects with asthma

Background The pathogenesis of asthma in obese subjects is poorly understood and has been described as a specific phenotype in these patients. Weight loss improves asthma control and lung function. Whether this improvement is the result of better mechanical properties of the airways or decreased systemic and bronchial inflammation remains unclear. Methods A longitudinal study in obese patients with asthma (bariatric surgery and asthma group (BS+A), n=27) and obese control (bariatric surgery without asthma group (BS−A), n=39) subjects undergoing bariatric surgery, and obese patients with asthma without intervention (no bariatric surgery and asthma group (NBS+A), n=12). Lung function, asthma control, cellular infiltrates in bronchial biopsies and circulating markers of systemic inflammation were measured during follow up at 3, 6 and 12 months. Results Bariatric surgery resulted in a profound weight loss at 12 months. In the BS+A group as well as the BS−A group FEV1, functional residual capacity, total lung capacity improved, whereas FEV1/FVC only improved in the BS−A group. In addition, Asthma Control Questionnaire (ACQ), Asthma Quality of Life Questionnaire, inhaled corticosteroid use and PD20 improved in BS+A, whereas in the NBS+A group only ACQ improved. Small airway function R5–R20 improved in both surgery groups, however the change in the BS+A group was greater, resulting in a comparable R5–R20 between BS+A and BS−A at 12-month follow-up. Besides improvement of systemic inflammation (high sensitivity C-reactive protein, adiponectin and leptin) after BS, only a decrease in mast cell numbers was detectable in the BS+A group. Conclusions Bariatric surgery improved small airway function, decreased systemic inflammation and number of mast cells in the airways. These effects could explain the improvement of asthma control, quality of life and lung function. Therefore bariatric surgery, in addition to all other positive effects, also improves asthma in subjects with morbid obesity. Trial registration number 3204.

Modulation of neurotrophin and neurotrophin receptor expression in nasal mucosa after nasal allergen provocation in allergic rhinitis.

Background:  Patients with allergic rhinitis (AR) feature both allergic airway inflammation and a hyperresponsiveness to nonspecific stimuli which is partly neuronally controlled. Still, it is unclear whether or not neurotrophins are involved in airway pathophysiology of AR and in nasobronchial interaction.

Desloratadine reduces systemic allergic inflammation following nasal provocation in allergic rhinitis and asthma patients

Background:  Preclinical studies have demonstrated that some second‐generation antihistamines have anti‐inflammatory effects. It is not known whether these effects are also demonstrable in vivo. In this study we investigated the effect of treatment with desloratadine (DL) on systemic inflammation and on nasal and bronchial mucosal inflammation after nasal allergen provocation (NP) in subjects with grass‐pollen‐allergic rhinitis and asthma.

Internet-based tapering of oral corticosteroids in severe asthma: a pragmatic randomised controlled trial

Background In patients with prednisone-dependent asthma the dose of oral corticosteroids should be adjusted to the lowest possible level to reduce long-term adverse effects. However, the optimal strategy for tapering oral corticosteroids is unknown. Objective To investigate whether an internet-based management tool including home monitoring of symptoms, lung function and fraction of exhaled nitric oxide (FENO) facilitates tapering of oral corticosteroids and leads to reduction of corticosteroid consumption without worsening asthma control or asthma-related quality of life. Methods In a 6-month pragmatic randomised prospective multicentre study, 95 adults with prednisone-dependent asthma from six pulmonary outpatient clinics were allocated to two tapering strategies: according to conventional treatment (n=43) or guided by a novel internet-based monitoring system (internet strategy) (n=52). Primary outcomes were cumulative sparing of prednisone, asthma control and asthma-related quality of life. Secondary outcomes were forced expiratory volume in 1 s (FEV1), exacerbations, hospitalisations and patients satisfaction with the tapering strategy. Results Median cumulative sparing of prednisone was 205 (25–75th percentile −221 to 777) mg in the internet strategy group compared with 0 (−497 to 282) mg in the conventional treatment group (p=0.02). Changes in prednisone dose (mixed effect regression model) from baseline were −4.79 mg/day and +1.59 mg/day, respectively (p<0.001). Asthma control, asthma-related quality of life, FEV1, exacerbations, hospitalisations and satisfaction with the strategy were not different between groups. Conclusions An internet-based management tool including home monitoring of symptoms, lung function and FENO in severe asthma is superior to conventional treatment in reducing total corticosteroid consumption without compromising asthma control or asthma-related quality of life. Clinical trial registration number Clinical trial registered with http://www.trialregister.nl (Netherlands Trial Register number 1146).

Utility of nitric oxide for the diagnosis of asthma in an allergy clinic population.

Fractionated exhaled nitric oxide (FeNO) expression is increased in airway inflammation and several studies have suggested that FeNO measurement can be useful in patients with asthma. Atopic individuals have increased FeNO levels, indicating that atopy may be a codeterminant in FeNO production. The aim of this study was to determine the discriminative value of FeNO for asthma and other atopic conditions in the general allergy clinic. Patients referred to the outpatient allergy clinic were screened. A standardized questionnaire was taken and atopic status was assessed (skin-prick test or specific plasma IgE). FeNO level and spirometry were measured. If the patients history was suspect for asthma, a provocative concentration causing a 20% decrease in forced expiratory volume in 1 second (PC(20)) histamine challenge followed. One hundred fourteen steroid-naive patients were included. Forty-two subjects were diagnosed as asthmatic patients and 72 were diagnosed as nonasthmatic patients, comprising patients with allergic rhinitis (n = 32), nonallergic rhinitis (n = 11), urticaria (n = 11), eczema (n = 7), and other (n = 11). Asthmatic patients had a higher FeNO level than nonasthmatic patients (44 ppb versus 17 ppb; p < 0.001). Receiver operating characteristic curve analysis revealed the optimal FeNO level to distinguish asthma from nonasthma at 27 ppb, with a sensitivity of 78%, specificity of 92%, a positive predictive value of 86%, and a negative predictive value of 87%. Increased FeNO was positively correlated with the presence of respiratory symptoms (p < 0.01), airflow reversibility (p < 0.001), total IgE (p < 0.001), and negatively correlated with PC(20) histamine (p = 0.019). Multivariate analysis revealed that atopy was not a significant predictor of FeNO in asthmatic patients. Measuring FeNO is a simple and useful test to differentiate new asthma patients from those with other atopic conditions in a general allergy clinic.

Evaluation of new laboratory tests to discriminate bacterial from nonbacterial chronic obstructive pulmonary disease exacerbations.

Discriminating bacterial from nonbacterial acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is difficult, causing antibiotics overuse and bacterial resistance. Sputum cultures are of limited use because results take time. In our hospital, only leukocyte concentration and CRP are laboratory parameters evaluated in AECOPD. We evaluated additional tests to discriminate bacterial vs. nonbacterial AECOPD: 5‐part leukocyte differentiation (hematology analyzer), leukocyte differentiation using flow cytometry (Leukoflow, Cytodiff), Leuko64 kit, and procalcitonin.

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.