Fraction of exhaled nitric oxide is associated with disease burden in the German Asthma Net severe asthma cohort

Abstract

The fraction of exhaled nitric oxide (F ENO ) is a biomarker for type 2 asthma, reflecting the degree of local pulmonary inflammation linked to immune pathways, including interleukin (IL)-13 [1]. In clinical practice, F ENO is a reliable marker for inhaled corticosteroid (ICS) responsiveness [2] and the efficacy of biological therapies, such as those targeting IL-4/IL-13 pathways [3, 4], as well as the detection of steroid nonadherence or resistance in severe asthma [2]. The prospective Severe Asthma Registry of the German Asthma Net (GAN) enrols patients with severe asthma for in-depth assessment of phenotypes, underlying mechanisms and therapeutic strategies; GAN has been approved by respective ethics committees, with all included patients having signed informed consent [5]. Prior studies of F ENO either included patients with asthma of any severity [6] or did not involve a comprehensive analysis in a large cohort [7]. We therefore used cross-sectional data from GAN to determine the correlation of F ENO with epidemiological, laboratory, clinical, lung function, or quality of life parameters and the need for oral corticosteroid (OCS) maintenance therapy in a carefully selected severe asthma cohort to better characterise the severe asthma subtype with high F ENO values.At the time of data acquisition (October 2019), GAN included 1689 patients with severe asthma, as defined by the European Respiratory Society/American Thoracic Society [1], from multiple tertiary referral centres, mainly in Germany, but also in Slovenia, Austria and Croatia [5]. F ENO was measured using any available device, according to the manufacturer's instructions [8]. Patients were included in the analysis if a F ENO measurement was available and excluded only if essential data were missing. Consistent with German and international guidelines [1, 9], F ENO values ⩾25 ppb were considered elevated; exacerbations were defined as events requiring OCS for ⩾3 days, doubling of established OCS dose, or hospitalisation; and thresholds for lung function parameters and exacerbation frequency were established. Controlled asthma was defined by Asthma Control Questionnaire-5 (ACQ-5) score <1.5, or Asthma Control Test (ACT) score ⩾20, with better asthma quality of life defined by mini Asthma Quality of Life Questionnaire (mAQLQ) score ⩾5.4 [1, 9]. Hypoxaemia was defined as partial pressure of oxygen in the blood (P O 2 ) <72 mmHg, and obesity as body mass index (BMI) ⩾30 kg•m −2 . Total IgE cut-off was aligned with the German criteria for anti-IgE therapy of 75 U•mL −1 [9]. Information bias was addressed by requiring an online form to be completed on assessment of the patient. The study was approved by the ethics committee of the Medical University of Vienna (EK 1849/2019), as well as by further local committees as per local requirements. Since the registry was initiated as a longitudinal project, data acquisition was not selective or biased towards any hypotheses. The significance level for hypothesis testing was set to 0.05. Due to the exploratory charac...

S2k-Leitlinie zur fachärztlichen Diagnostik und Therapie von Asthma 2023

“…Auch die passive Exposition mit Zigarettenrauch hat einen negativen Einfluss auf die Lungenfunktion, insbesondere in der frühen Kindheit und durch die Mutter während der Schwangerschaft (dieser Effekt beruht nicht auf einer Förderung von Allergien) [42]. Akute Tabakrauchexposition senkt die FeNO-Werte bei Patienten mit Asthma [43]. Die Bedeutung einer chronischen Tabakrauchexposition für die Asthma-typische Atemwegsentzündung und die Typ-2-Marker-Expression (wie Eosinophile oder FeNO) ist weniger klar, da bei Patienten mit schwerem Asthma und erheblicher Rauchanamnese (> 10 Packungsjahre) eine starke Typ-2-Marker-Expression nicht selten ist [44,45].…”

Exhaled Biomarkers for Point-of-Care Diagnosis: Recent Advances and New Challenges in Breathomics

“…Physiological changes, such as exercise, have also been shown to cause a change in the breathprint detected by the e-nose, and this was confirmed by the changes in VOCs determined by mass spectrometry [ 60 , 291 , 292 ]. There is an expert consensus-based recommendation for technical standards to be applied when using e-noses for exhaled breath testing [ 293 ].…”

Update on the Role of FeNO in Asthma Management

“…Elevated FeNO levels have also been associated with asthma control and risk of asthma exacerbation [ 31 ]. In a German cohort of individuals with severe asthma where elevated FeNO levels were associated with poor asthma control, lower lung function and increased frequency of asthma exacerbations [ 32 ]. In this study, FeNO levels of ≥25 ppb had 65% sensitivity in predicting two or more annual exacerbations.…”