Background: Asthma is a chronic respiratory disease comprising different pheno‐ and endotypes. Diagnostic tools for the identification of allergic versus non‐allergic asthma are needed for new precision medicine‐based treatments. Objective: To determine IgE sensitization profiles to multiple micro‐arrayed allergen molecules in adult patients with asthma in the Austrian LEAD (Lung, hEart, sociAl, boDy) cohort; to compare IgE‐ and non‐IgE sensitized patients with asthma; and to define possible allergen‐specific immunotherapy concepts for sensitized patients. Methods: Out of 893 patients with a history of asthma, patients with current asthma ( n = 436) were analyzed for IgE sensitizations to 110 micro‐arrayed molecules from airborne and food allergen sources and by skin prick testing (SPT) with 10 allergen extracts (English plantain, mugwort, ragweed, timothy grass, ash tree, mites, dog, cat, Alternaria alternata , and Fagales mix). Clinical asthma‐related parameters were compared between patients with IgE sensitization to asthma allergen molecules and non‐IgE sensitized patients with asthma. Results: IgE sensitization was detected in 73.2% of patients with asthma using 63 micro‐arrayed respiratory allergens. The most recognized respiratory outdoor allergen molecules were Bet v 1 (32.8%) and Ole e 1 (23.2%) followed by grass pollen, ragweed, and mugwort allergens. Fel d 1 was the most frequently recognized respiratory indoor allergen molecule (42.7%) followed by house dust mite and dog allergen molecules. Micro‐arrayed allergens allowed the identification of IgE reactivity profiles indicative of genuine sensitizations to different allergen sources. IgE‐sensitized patients were significantly younger than non‐IgE‐sensitized patients with asthma (median age 44 versus 58 years). Patients sensitized to respiratory allergens showed significantly better lung function (FEV1, FVC and FEV/FVC) and less dyspnea but more allergic bronchitis than non‐IgE‐sensitized patients with asthma. More IgE‐sensitized patients used antihistamines but fewer inhaled corticosteroids than non‐IgE‐sensitized patients with asthma. Interestingly, eosinophil counts were lower both in ICS‐treated as well as untreated sensitized patients than in non‐sensitized patients with asthma. Conclusion: Molecular allergy diagnosis allowed the detection of genuine IgE sensitizations in adult patients with asthma; enabling stratification for precision medicine‐based forms of personalized treatments such as allergen‐based immunotherapy (AIT) and/or administration of biological treatments in asthma.

Background and Objective: This study aims to assess the prevalence and longitudinal transitions of spirometric patterns defined by the lower limit of normal ( LLN ) criteria: normal airflow ( FEV ₁ / FVC ≥ LLN , FEV ₁ ≥ LLN ); preserved ratio impaired spirometry ( PRISm ; FEV ₁ / FVC ≥ LLN , FEV ₁ < LLN ); or obstruction ( FEV ₁ / FVC < LLN ). Methods: Post‐bronchodilator values of pulmonary function tests in the transitional states of these spirometric patterns were examined in the population‐based Austrian LEAD study at visits 1 ( V1 ) and 2 ( V2 ). 7232 (aged ≥ 18 years) were re‐examined after 4.3 ± 0.6 years and categorized into different spirometric patterns. Changes in static lung volumes and flow rates were additionally examined to better characterize changes in spirometric patterns and associated spirometric measurements. Results: Whilst abnormal spirometry was found in 6.7% individuals at baseline, the prevalence of PRISm (2.2% and 1.6%), but not obstruction (4.5% and 6.1%), remained consistent over time (V1 and V2 respectively). Individuals with PRISm‐V1 exhibited substantial rates of transition (48.9%) whilst individuals with obstruction‐ V1 remained relatively stable (77.8%). Most individuals who reverted from obstruction to improved spirometry had baseline FEV1 / FVC values closer to the LLN threshold (optimal cut‐off: 64.5%) while those who progressed to obstruction had an optimal predicted threshold of approximately 75%. Changes in pulmonary function tests over time were substantially different between transitional states, and notably more so in those with incident PRISm compared to incident obstructive individuals. Conclusion: We demonstrate the changes in lung function in different transitional states of spirometric patterns over time which thereby illustrate the need for repeated spirometric assessments combined with lung volume measurements for accurate monitoring and diagnosis. image

The utility of fractional exhaled nitric oxide (FeNO) was evaluated alongside blood eosinophils in phenotyping mild asthma. Inclusion of FeNO improved classification accuracy and calibration in an adapted ISAR-based model; however, its predictive improvement was modest and its susceptibility to transient elevations suggests limited added value for routine clinical classification. Simplified algorithms may offer more accurate phenotyping in population-based settings with real-world constraints.

One aspect of reproducibility in preclinical research that is frequently overlooked is the physical condition in which physiological, pharmacological, or behavioural recordings are conducted. In this study, the physical conditions of mice were altered through the attachments of wireless electrophysiological recording devices (Neural Activity Tracker-1, NAT-1). NAT-1 devices are miniaturised multichannel devices with onboard memory for direct high-resolution recording of brain activity for >48 h. Such devices may limit the mobility of animals and affect their behavioural performance due to the added weight (total weight of approximately 3.4 g). The mice were additionally treated with saline (control), N-methyl-D-aspartate (NMDA) receptor antagonist MK801 (0.85 mg/kg), or the muscarinic acetylcholine receptor blocker scopolamine (0.65 mg/kg) to allow exploration of the effect of NAT-1 attachments in pharmacologically treated mice. We found only minimal differences in behavioural outcomes with NAT-1 attachments in standard parameters of locomotor activity widely reported for the open field test between the drug treatments. Hypoactivity was globally observed as a consistent outcome in the MK801-treated mice and hyperactivity in scopolamine groups regardless of NAT-1 attachments. These data collectively confirm the reproducibility for combined behavioural, pharmacological, and physiological endpoints even in the presence of lightweight wireless data loggers. The NAT-1 therefore constitutes a pertinent tool for investigating brain activity in, e.g., drug discovery and models of neuropsychiatric and/or neurodegenerative diseases with minimal effects on pharmacological and behavioural outcomes.

Background: In patients with airflow obstruction, the levels of biomarkers of Type-2 (T2) inflammation serve to predict the effectiveness of inhaled corticosteroid and biological therapies. Elevated biomarkers of T2 inflammation, including fractional exhaled nitric oxide (FeNO, ≥20 ppb) and blood eosinophil counts (BEC, ≥300 cells/µL), were investigated in a population-based cohort of the Austrian LEAD study. Methods: A total of 4976 individuals (aged 18–82 years) were categorised into four groups based on their FeNO and BEC levels: normal with FeNO < 20 ppb and BEC < 300 cells/µL (n = 2634); FeNO ≥ 20 ppb only (n = 1623); BEC ≥ 300 cells/µL only (n = 340); and FeNO ≥ 20 ppb and BEC ≥ 300 cells/µL (n = 379). Results: In age- and sex-adjusted regression models, individuals with elevated BEC only were most associated with chronic cough and sputum production (odds ratios [95% CI]: 1.22 [0.78, 1.84] and 1.37 [1.13, 2.62], respectively), whilst individuals with both elevated T2 biomarkers were most associated with wheezing, dyspnoea and asthma (odds ratios [95% CI]: 2.27 [1.56, 3.26], 1.32 [0.64, 2.50] and 3.63 [2.69, 4.88] respectively). Elevated levels of both FeNO and BEC presented an additive effect in extrapulmonary conditions, particularly in allergy, eczema and rhino conjunctivitis (odds ratios [95% CI]: 2.30 [1.84, 2.88], 1.37 [1.03, 1.81] and 2.95 [2.34, 3.70], respectively). Conclusions: T2 inflammation marked by elevated levels of FeNO and/or BEC is not only associated with respiratory conditions but also extends to extrapulmonary characteristics, with an additive effect.

Background: The pattern of preserved ratio impaired spirometry (PRISm) has gained increased attention in the last few years. While PRISm has been linked to increased morbidity and mortality, the underlying physiological causes remain unclear and the stability of PRISm over time remains uncertain. Methods: We investigated 6571 individuals (≥25 years, 51.4% female) from the Austrian population-based, longitudinal LEAD (Lung, hEart, sociAl, boDy) study who underwent post-bronchodilator spirometry and body plethysmography twice within a 4-year interval. Individuals were classified into normal spirometry (forced expiratory volume in 1 s (FEV ₁ )/forced vital capacity (FVC)≥0.7 and FEV ₁ ≥80% predicted Global Lung Function Initiative (GLI)); airflow limitation (AFL) (FEV ₁ /FVC<0.7); and PRISm (FEV ₁ /FVC≥0.7 and FEV ₁ <80% predicted GLI). Body composition was assessed by bone density scanning. Results: PRISm was present in 2.6% of individuals (n=171) at baseline. Different subgroups of PRISm were identified: after 4 years, 45.6% had persistent PRISm, 37.4% PRISm-to-normal and 17.0% had PRISm-to-AFL. Persistent PRISm individuals were characterised by significantly lower total lung capacity (TLC), with two-thirds meeting TLC criteria for restriction. PRISm-to-AFL had a higher TLC and lower airway conductance as well as a higher FEV ₁ decline. Participants with new PRISm after 4 years (n=71) had the highest decline of vital capacity and TLC. Smoking status was not associated with PRISm progression or resolution as never- and ever-smokers with PRISm showed no difference in frequency of transitions after 4 years. Conclusion: PRISm is primarily defined by low lung volumes and is characterised by a dynamic course, with more than two-thirds demonstrating stable or improving lung function. Lung volume assessment in PRISm is mandatory for precise evaluation of pulmonary function. Similar transition patterns in smokers and never-smokers challenge the assumption of PRISm as an early smoking-related obstructive state and emphasise the importance of repeated lung function testing over time.