Manual hyperinflation partly prevents reductions of functional residual capacity in cardiac surgical patients - a randomized controlled trial

Cardiac surgery is associated with post-operative reductions of functional residual capacity (FRC). Manual hyperinflation (MH) aims to prevent airway plugging, and as such could prevent the reduction of FRC after surgery. The main purpose of this study was to determine the effect of MH on post-operative FRC of cardiac surgical patients. This was a randomized controlled trial of patients after elective coronary artery bypass graft and/or valve surgery admitted to the intensive care unit (ICU) of a university hospital. Patients were randomly assigned to a "routine MH group" (MH was performed within 30 minutes after admission to the ICU and every 6 hours thereafter, and before tracheal extubation), or a "control group" (MH was performed only if perceptible (audible) sputum was present in the larger airways causing problems with mechanical ventilation, or if oxygen saturation (SpO2) dropped below 92%). The primary endpoint was the reduction of FRC from the day before cardiac surgery to one, three, and five days after tracheal extubation. Secondary endpoints were SpO2 (at similar time points) and chest radiograph abnormalities, including atelectasis (at three days after tracheal extubation). A total of 100 patients were enrolled. Patients in the routine MH group showed a decrease of FRC on the first post-operative day to 71% of the pre-operative value, versus 57% in the control group (P = 0.002). Differences in FRC became less prominent over time; differences between the two study groups were no longer statistically significant at Day 5. There were no differences in SpO2 between the study groups. Chest radiographs showed more abnormalities (merely atelectasis) in the control group compared to patients in the routine MH group (P = 0.002). MH partly prevents the reduction of FRC in the first post-operative days after cardiac surgery. Netherlands Trial Register (NTR): NTR1384. http://www.trialregister.n

Clinical and inflammatory markers in asthma and COPD phenotyping

Based on the studies described in this thesis, we conclude that adult-onset respiratory diseases (asthma and COPD) are heterogeneous conditions characterized by different clinical features and inflammatory characteristics. The first part of the thesis focused on phenotypes of adult-onset asthma. We showed that in patients with longstanding disease, three different clinical well-recognizable phenotypes can be identified, of which two are characterized by severe asthma. One of these severe asthma phenotypes can already be detected in the early stages of the disease. Furthermore, in newly diagnosed adult-onset asthma, CRS and nasal polyposis are associated with more severe airway inflammation. Therefore, this co-morbidity could be an early sign of severe asthma developing. Finally, measuring blood eosinophils is an accurate diagnostic tool for detecting this inflammatory phenotype in patients with asthma and is easy to measure in clinical practise. The second part of the thesis focused on new diagnostic tests to identify inflammatory phenotypes in patients with COPD. These patients might benefit from specific treatments but cannot be distinguished based on clinical characteristics. The mannitol challenge test and exhaled breath analysis are closely associated with the degree of airway inflammation. The tests are easy to perform and could be used in clinical practice to monitor airway inflammation

Adult-onset asthma: is it really different?

Asthma that starts in adulthood differs from childhood-onset asthma in that it is often non-atopic, more severe and associated with a faster decline in lung function. Understanding of the underlying mechanism of adult-onset asthma and identification of specific phenotypes may further our understanding of pathophysiology and treatment response, leading to better targeting of both existing and new approaches for personalised management. Pivotal studies in past years have led to sustained progress in many areas, ranging from risk factors for development, identification of different phenotypes, and introduction of new therapies. This review highlights and discusses literature on adult-onset asthma, with special focus on the differences from childhood-onset asthma, risk factors for development, phenotypes of adult-onset asthma and new approaches for personalised managemen

Diagnosing persistent blood eosinophilia in asthma with single blood eosinophil or exhaled nitric oxide level

Background: Eosinophilic asthma is characterized by persistently elevated blood eosinophils, adult-onset asthma and corticosteroid resistance. For stratified medicine purposes one single measurement of blood eosinophils or exhaled nitric oxide (FeNO) is commonly used. The aim of this study was to investigate in patients with new-onset asthma whether persistent blood eosinophilia can be predicted with one single measurement of these biomarkers. Methods: Blood eosinophils and exhaled nitric oxide levels were measured at yearly intervals over 5 years in 114 adults with new-onset asthma on inhaled corticosteroid treatment. Two definitions of persistent blood eosinophilia were used (1); blood eosinophils at every visit ≥0.30 × 109/L, or (2) ≥0.40 × 109/L. Receiver operating characteristic analyses were performed. Diagnostic cut-off values were defined at a positive predictive value of 95% (or the highest achievable). Results: Using definition 1 (blood eosinophils ≥0.30 × 109/L) the cut-off value for a single measurement of blood eosinophils was 0.47 × 109/L. For definition 2 (≥0.40 × 109/L) the cut-off value was 0.49 × 109/L. Cut-off values for persistently low blood eosinophils were 0.17 × 109/L for definition (1) and 0.21 × 109/L for definition (2), respectively. For FeNO no cut-off values with sufficient accuracy could be defined. Conclusion: We showed that by using high and low cut-off values, one single measurement of blood eosinophils, but not FeNO in the initial phase of new-onset asthma in adults can be used to predict persistence or absence of blood eosinophilia in asthma

New-Onset Asthma in Adults: What Does the Trigger History Tell Us?

Background: Adult-onset asthma is an important asthma phenotype and, in contrast to childhood asthma, is often associated with specific triggers of onset. It is unknown whether these triggers correspond with specific phenotypic characteristics or predict a specific asthma outcome. Objective: To compare clinical, functional, and inflammatory characteristics between patients with different triggers of asthma onset, and relate these triggers to asthma outcome. Methods: Two hundred adults with recently diagnosed (10 patients. Results: Ten categories of triggers were identified, of which 5 contained >10 patients. Clinical and inflammatory characteristics and remission rates differed significantly between categories. “New allergic sensitization” (11%) was associated with mild atopic asthma and a relatively young age at onset; “pneumonia” (8%) with previous smoking, low IgE, and the highest remission rates (one third); “upper respiratory symptoms” (22%) with high exhaled NO and eosinophilia; “no trigger identified” (38%) did not show any specific characteristics; and “stressful life event” (7%) with high medication usage, low type 2 markers, and no disease remission. Conclusions: Patients with adult-onset asthma can be characterized by the trigger that seemingly incited their asthma. These triggers might represent underlying mechanisms and may be important to phenotype patients and predict disease outcome

Predictors of accelerated decline in lung function in adult-onset asthma

-2We conclude that adults with new-onset asthma with both high levels of exhaled nitric oxide and low BMI are at risk of accelerated decline in lung functio

Clinical predictors of remission and persistence of adult-onset asthma

Background: Adult-onset asthma is an important but relatively understudied asthma phenotype and little is known about its natural course and prognosis. The remission rate is believed to be low, and it is still obscure which factors predict remission or persistence of the disease. Objective: This study sought to determine the remission rate and identify predictors of persistence and remission of adult-onset asthma. Methods: Two hundred adult patients with recently diagnosed ( = 1 year and no asthma medication use for >= 1 year. Descriptive statistics and logistic regression analysis were performed. Results: Five-year follow-up data of 170 patients (85%) was available. Of these, 27 patients (15.9%) experienced asthma remission. Patients with asthma persistence were older, had worse asthma control, required higher doses of inhaled corticosteroids, had more severe airway hyperresponsiveness, more often nasal polyps, and higher levels of blood neutrophils as compared to patients who experienced clinical remission. In a multivariable logistic regression analysis, only moderate to severe bronchial hyperresponsiveness and nasal polyps were independent predictors of asthma persistence. Patients with these 2 characteristics had <1% chance of asthma remission. Conclusions: One in 6 patients with adult-onset asthma experiences remission within the first 5 years of the disease. In patients with moderate to severe bronchial hyperresponsiveness and nasal polyposis, the chance of remission is close to zer

Predictors for the development of progressive severity in new-onset adult asthma

A proportion of patients with adult-onset asthma have severe disease. Risk factors for an increase in asthma severity are poorly known. We sought to identify predictors for the development of severe asthma in adults. A cohort of 200 adults with new-onset asthma was prospectively followed for 2 years. At baseline, patients underwent a comprehensive assessment of clinical, functional, and inflammatory parameters. After 2 years, change in asthma severity was assessed by using the Global Initiative for Asthma score (range, 1-4), which is based on asthma control (Asthma Control Questionnaire), lung function (FEV1), and inhaled corticosteroid requirement. ANOVA and multiple regression equations were used in the analysis. One hundred twenty-eight patients completed 2 years of follow-up. Seventeen (13.3%) patients had an increase in asthma severity, whereas 53 (41.4%) patients had a decrease. A lower postbronchodilator FEV1/forced vital capacity ratio and a higher number of cigarette pack years smoked at baseline were significantly associated with an increase in asthma severity at follow-up. Multiple regression equations showed that only the number of cigarette pack years smoked was independently associated with an increase in asthma severity, with an odds ratio of 1.4 (95% CI, 1.02-1.91) for every 10 pack years smoked. A history of cigarette smoking in patients with new-onset adult asthma predicts an increase in asthma severity during the first 2 years of the disease in a dose-dependent manne

Predictors of frequent exacerbations in (ex)smoking and never smoking adults with severe asthma

Persistent eosinophilic airway inflammation is an important driver for asthma exacerbations in non-smokers with asthma. Whether eosinophilic inflammation is also a predictor of asthma exacerbations in (ex)smokers is not known. The aim was to investigate factors associated with frequent exacerbations in never smokers and (ex)smokers with asthma. (Ex)smoking (n = 83) and never smoking (n = 70) patients with uncontrolled asthma despite high dose asthma medication (GINA treatment step 4-5) were selected from a cohort of 571 adult-onset asthma patients. Clinical, functional and inflammatory parameters were used in multivariate logistic regression analyses to identify factors associated with frequent exacerbations (≥3 oral corticosteroid (OCS) bursts in the previous year). Frequent exacerbations in (ex)smokers were independently associated with ICS dose (OR 1.2, 95%CI: 1.1-1.3) and blood neutrophil count (OR 1.5, 95%CI: 1.2-2.1). In never smokers frequent exacerbations were independently associated with blood eosinophil count (OR 18.9, 95%CI: 1.8-202.1). This study shows that never smoking and (ex)smoking patients with severe asthma have different predictors of frequent exacerbations: higher blood neutrophils in (ex)smokers versus higher blood eosinophils in never smokers. This suggests that different types of systemic background inflammation play a role in the aetiology of exacerbations in these patients. Netherlands Trial Register: NTR2217, NTR1846 and NTR183

Clinical profile of patients with adult-onset eosinophilic asthma

Adult-onset eosinophilic asthma is increasingly recognised as a severe and difficult-to-treat subtype of asthma. In clinical practice, early recognition of patients with this asthma subtype is important because it may have treatment implications. Therefore, physicians need to know the distinct characteristics of this asthma phenotype. The objective of the present study was to determine the characteristic profile of patients with adult-onset eosinophilic asthma. 130 patients with adult-onset (>18 years of age) asthma and high blood eosinophil counts (≥0.3×109 L−1) were compared with 361 adult-onset asthma patients with low (<0.3×109 L−1) blood eosinophils. Measurements included a series of clinical, functional and imaging parameters. Patients with high blood eosinophils were more often male, had less well controlled asthma and higher exacerbation rates, despite the use of higher doses of inhaled corticosteroids. They had higher levels of total IgE without more sensitisation to common inhaled allergens. In addition, these patients had worse lung function, and more often showed fixed airflow limitation, air trapping, nasal polyposis and abnormalities on sinus computed tomography scanning. Chronic rhinosinusitis, air trapping and male sex were three independent factors associated with blood eosinophilia (adjusted OR 3.8 (95% CI 1.7–8.1), 3.0 (95% CI 1.1–8.1) and 2.4 (95% CI 1.3–4.4), respectively). Patients with adult-onset asthma with elevated blood eosinophils exhibit a distinct profile, which can readily be recognised in clinical practice