The Fractional exhaled Nitric Oxide (FeNO)- test as add-on test in the diagnostic work-up of asthma:a study protocol

Background: Asthma is a common disease characterized by chronic inflammation of the lower airways, bronchial hyperactivity, and (reversible) airway obstruction. The Global Initiative of Asthma Guideline recommends a flowchart to diagnose asthma with first-step spirometry with reversibility and a bronchial challenge test (BPT) with histamine or methacholine as a second step [1]. The BPT is considered burdensome, time-consuming for patients and staff, can cause side effects, and is expensive. In addition, this test strongly encumbers lung function capacity. Elevated Nitric Oxide (NO) is associated with airway eosinophilic inflammation in asthma patients and can be measured in exhaled air with the Fractional exhaled (Fe) NO-test. This low-burden FeNO-test could be used as an ‘add-on’ test in asthma diagnostics [2, 3]. Methods and analysis: This multi-center prospective study (Trial number: NCT06230458) compares the ‘standard asthma diagnostic work-up’ (spirometry with reversibility and BPT) to the ‘new asthma diagnostics work-up’ (FeNO-test as an intermediate step between the spirometry with reversibility and the BPT), intending to determine the impact of the FeNO-based strategy, in terms of the number of avoided BPTs, cost-effectiveness and reduced burden to the patient and health care. The cost reduction of incorporating the FeNO-test in the new diagnostic algorithm will be established by the number of theoretically avoided BPT. The decrease in burden will be studied by calculating differences in the Visual Analogue Scale (VAS) -score and Asthma Quality of Life Questionnaire (AQLQ) -score after the BPT and FeNO-test with an independent T-test. The accuracy of the FeNO-test will be calculated by comparing the FeNO-test outcomes to the (gold standard) BPTs outcomes in terms of sensitivity and specificity. The intention is to include 171 patients. Ethics and dissemination: The local medical ethics committee approved the proposed study and is considered a low-burden and risk-low study. The local medical ethics committee registration number: R23.005. Strengths and limitations of this study: Strengths: This is the first study that investigates the value of the FeNO-test (cut off ≥ 50 ppb) as an add-on test, to determine the impact of the FeNO-based strategy, in terms of the number of avoided BPTs, cost-effectiveness, and reduced burden on the patient and health care. Limitations: High FeNO levels may also be observed in other diseases such as eosinophilic chronic bronchitis and allergic rhinitis. The FeNO-test can be used to rule in a diagnosis of asthma with confidence, however, due to the poor sensitivity it is not suitable to rule out asthma.</p

The Fractional exhaled Nitric Oxide (FeNO)- test as add-on test in the diagnostic work-up of asthma:a study protocol

Background: Asthma is a common disease characterized by chronic inflammation of the lower airways, bronchial hyperactivity, and (reversible) airway obstruction. The Global Initiative of Asthma Guideline recommends a flowchart to diagnose asthma with first-step spirometry with reversibility and a bronchial challenge test (BPT) with histamine or methacholine as a second step [1]. The BPT is considered burdensome, time-consuming for patients and staff, can cause side effects, and is expensive. In addition, this test strongly encumbers lung function capacity. Elevated Nitric Oxide (NO) is associated with airway eosinophilic inflammation in asthma patients and can be measured in exhaled air with the Fractional exhaled (Fe) NO-test. This low-burden FeNO-test could be used as an ‘add-on’ test in asthma diagnostics [2, 3]. Methods and analysis: This multi-center prospective study (Trial number: NCT06230458) compares the ‘standard asthma diagnostic work-up’ (spirometry with reversibility and BPT) to the ‘new asthma diagnostics work-up’ (FeNO-test as an intermediate step between the spirometry with reversibility and the BPT), intending to determine the impact of the FeNO-based strategy, in terms of the number of avoided BPTs, cost-effectiveness and reduced burden to the patient and health care. The cost reduction of incorporating the FeNO-test in the new diagnostic algorithm will be established by the number of theoretically avoided BPT. The decrease in burden will be studied by calculating differences in the Visual Analogue Scale (VAS) -score and Asthma Quality of Life Questionnaire (AQLQ) -score after the BPT and FeNO-test with an independent T-test. The accuracy of the FeNO-test will be calculated by comparing the FeNO-test outcomes to the (gold standard) BPTs outcomes in terms of sensitivity and specificity. The intention is to include 171 patients. Ethics and dissemination: The local medical ethics committee approved the proposed study and is considered a low-burden and risk-low study. The local medical ethics committee registration number: R23.005. Strengths and limitations of this study: Strengths: This is the first study that investigates the value of the FeNO-test (cut off ≥ 50 ppb) as an add-on test, to determine the impact of the FeNO-based strategy, in terms of the number of avoided BPTs, cost-effectiveness, and reduced burden on the patient and health care. Limitations: High FeNO levels may also be observed in other diseases such as eosinophilic chronic bronchitis and allergic rhinitis. The FeNO-test can be used to rule in a diagnosis of asthma with confidence, however, due to the poor sensitivity it is not suitable to rule out asthma.</p

Differentiating interstitial lung diseases from other respiratory diseases using electronic nose technology

Introduction: Interstitial lung disease (ILD) may be difficult to distinguish from other respiratory diseases due to overlapping clinical presentation. Recognition of ILD is often late, causing delay which has been associated with worse clinical outcome. Electronic nose (eNose) sensor technology profiles volatile organic compounds in exhaled breath and has potential to detect ILD non-invasively. We assessed the accuracy of differentiating breath profiles of patients with ILD from patients with asthma, chronic obstructive pulmonary disease (COPD), and lung cancer using eNose technology. Methods: Patients with ILD, asthma, COPD, and lung cancer, regardless of stage or treatment, were included in a cross-sectional study in two hospitals. Exhaled breath was analysed using an eNose (SpiroNose) and clinical data were collected. Datasets were split in training and test sets for independent validation of the model. Data were analyzed with partial least squares discriminant and receiver operating characteristic analyses. Results: 161 patients with ILD and 161 patients with asthma (n = 65), COPD (n = 50) or lung cancer (n = 46) were included. Breath profiles of patients with ILD differed from all other diseases with an area under the curve (AUC) of 0.99 (95% CI 0.97–1.00) in the test set. Moreover, breath profiles of patients with ILD could be accurately distinguished from the individual diseases with an AUC of 1.00 (95% CI 1.00–1.00) for asthma, AUC of 0.96 (95% CI 0.90–1.00) for COPD, and AUC of 0.98 (95% CI 0.94–1.00) for lung cancer in test sets. Results were similar after excluding patients who never smoked. Conclusions: Exhaled breath of patients with ILD can be distinguished accurately from patients with other respiratory diseases using eNose technology. eNose has high potential as an easily accessible point-of-care medical test for identification of ILD amongst patients with respiratory symptoms, and could possibly facilitate earlier referral and diagnosis of patients suspected of ILD.</p

Implementing integrated care guidelines in asthma and COPD:It ain’t easy!

Objective: To evaluate the implementation of a guideline-based, integrated, standardised, personal approach in patients with Chronic ObstructivePulmonary Disease (COPD) or Asthma in a real-life situation.Methods: Patients at the outpatient clinic of the department of pulmonary disease were included in a controlled cohort study, comparing the use ofdiagnostic items and ‘Personalised care plans’ (PCPs) in patients with obstructive lung disease before (2013) and after (2015) implementation of apersonalised diagnostic pathway. Results were compared with reference data (2016) from two control hospitals that used the same guidelines butdid not implement this pathway.Results: 100 patients were selected for all three cohorts. After implementing the diagnostic pathway in 2015, 35 % of patients visited attended allpre-planned appointments, whereas 65 % of patients did not: they were diagnosed using usual care. Factors contributing to patients not attendingthe diagnostic care pathway were: the logistical complexity and intensity of the 2-day pathway, patients willingness to participate in a personalisedpathway, and low social economic status or low literacy. After the implementation of the pathway, a significant improvement was seen in thenumber of PCPs (P &lt; 0.001) and the number of diagnostic items registered recorded in the patients’ electronic medical records (P &lt; 0.001).Conclusion: Implementing a standardised diagnostic pathway in a real-life population significantly improved the number of personalised care plans,demonstrating that the implementation of holistic care planning is feasible in this population. Nevertheless, the pathway needs further improvements to maximize the number of patients benefitting from it, including logistical streamlining, removing unnecessary diagnostic tools, andincreasing the focus on low literacy. Additionally, we found that implementing existing guidelines in a real life context is complex. Therefore, it isrequired to prioritize the translation of current guidelines into every-day practice, before expanding existing guidelines and protocol

Measuring burden of disease in both asthma and COPD by merging the ACQ and CCQ:less is more?

Symptoms of asthma and COPD often overlap, and both diseases can co-exist in one patient. The asthma control questionnaire (ACQ) and clinical COPD questionnaire (CCQ) were developed to assess disease burden in respectively asthma or COPD. This study explores the possibility of creating a new questionnaire to assess disease burden in all obstructive lung diseases by integrating and reducing questions of the ACQ and CCQ. Data of patients with asthma, COPD and asthma-COPD overlap (ACO) were collected from a primary and secondary care center. Patients completed ACQ and CCQ on the same day. Linear regression tested correlations. Principal Component Analysis (PCA) was used for item reduction. The secondary cohort with asthma and COPD patients was used for initial question selection (development cohort). These results were reproduced in the primary care cohort and secondary cohort of patients with ACO. The development cohort comprised 252 patients with asthma and 96 with COPD. Correlation between ACQ and CCQ in asthma was R = 0.82, and in COPD R = 0.83. PCA determined a selection of 9 questions. Reproduction in primary care data (asthma n = 1110, COPD n = 1041, ACO = 355) and secondary care data of ACO patients (n = 53) resulted in similar correlations and PCA-derived selection of questions. In conclusion, PCA determined a selection of nine questions of the ACQ and CCQ: working title ‘the Obstructive Lung Disease Questionnaire’. These results suggest that this pragmatic set of questions might be sufficient to assess disease burden in obstructive lung disease in both primary as secondary care.</p

SARS-Cov-2: The Relevance and Prevention of Aerosol Transmission

Coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), has claimed many victims worldwide due to its high virulence and contagiousness. The person-to-person transmission of SARS-Cov-2 when in close contact is facilitated by respiratory droplets containing the virus particles, and by skin contact with contaminated surfaces. However, the large number of COVID-19 infections cannot be explained only by droplet deposition or contact contamination. It seems very plausible that aerosols are important in transmitting SARS-Cov-2. It has been demonstrated that SARS-CoV-2 remains viable in aerosols for hours, facilitating rapid distribution of the virus over great distances. Aerosols may, therefore, also be responsible for so-called super-spreader events. Indirect evidence points to a correlation between ventilation and the transmission and spread of SARS-Cov-2, supporting ventilation as an important factor in preventing airborne transmission. Further actions to avoid transmission of COVID-19 include social distancing, hygiene measures, and barrier measures, such as face-coverings. Professional masks offer better protection than cloth masks. These protection measures are especially relevant to health care workers, when performing endotracheal intubation, but the risk from non-invasive ventilation and nebulizing treatment seems to be moderate

Diagnostic differentiation between asthma and COPD in primary care using lung function testing

Asthma and COPD are defined as different disease entities, but in practice patients often show features of both diseases making it challenging for primary care clinicians to establish a correct diagnosis. We aimed to establish the added value of spirometry and more advanced lung function measurements to differentiate between asthma and COPD. A cross-sectional study in 10 Dutch general practices was performed. 532 subjects were extensively screened on respiratory symptoms and lung function. Two chest physicians assessed if asthma or COPD was present. Using multivariable logistic regression analysis we assessed the ability of three scenarios (i.e. only patient history; diagnostics available to primary care; diagnostics available only to secondary care) to differentiate between the two conditions. Receiver operator characteristics (ROC) curves and area under the curve (AUC) were calculated for each scenario, with the chest physicians' assessment as golden standard. Results showed that 84 subjects were diagnosed with asthma, 138 with COPD, and 310 with no chronic respiratory disease. In the scenario including only patient history items, ROC characteristics of the model showed an AUC of 0.84 (95% CI 0.78-0.89) for differentiation between asthma and COPD. When adding diagnostics available to primary care (i.e., pre- and postbronchodilator spirometry) AUC increased to 0.89 (95% CI 0.84-0.93; p = 0.020). When adding more advanced secondary care diagnostic tests AUC remained 0.89 (95% CI 0.85-0.94; p = 0.967). We conclude that primary care clinicians' ability to differentiate between asthma and COPD is enhanced by spirometry testing. More advanced diagnostic tests used in hospital care settings do not seem to provide a better overall diagnostic differentiation between asthma and COPD in primary care patients

Intrinsic factors influence self-management participation in COPD: effects on self-efficacy

Public Health and primary carePrevention, Population and Disease management (PrePoD

Intrinsic factors influence self-management participation in COPD: effects on self-efficacy

Public Health and primary carePrevention, Population and Disease management (PrePoD