The IL-36 subfamily, a member of the IL-1 superfamily, is thought to promote type 2 (T2) and non-T2 inflammation and involved in autoimmune and airway disease progression. However, its role in asthma remains unclear.

We sought to determine the contribution of the IL-36 subfamily to the clinical manifestation of asthma.

The levels of serum IL-36α, IL-36β, and IL-36γ, recognized as IL-36 subfamily agonists, and IL-36 receptor antagonist (IL-36Ra) and IL-38, recognized as IL-36 subfamily antagonists, were measured by ELISA in 110 asthma patients (55 with nonsevere and 55 with severe asthma) aged ≥20 years and 31 healthy individuals. The association of IL-36 with clinical indices and inflammatory mediators was examined. The characteristics of high and low IL-36 subgroups were explored.

IL-36α, IL-36γ, and IL-36Ra levels were significantly higher in asthma patients, especially patients with severe asthma, than in healthy controls. The high IL-36γ group exhibited lower Asthma Control Test scores (P = .01), more frequent asthma exacerbations (AEs), and higher hazard ratio for AEs. The high IL-36Ra group exhibited higher values of forced expiratory volume in 1 second, more frequent severe AEs, and higher hazard ratio for severe exacerbations. The IL-36 cytokine levels, except for IL 36α, were positively correlated with IL-6, IL-13, IL-17, and/or IFN-γ levels. IL-36Ra was positively correlated with age-adjusted forced expiratory volume and forced vital capacity.

A systemically high IL-36 level is associated with asthma severity and with both T2 and non-T2 cytokines, and it implies poor condition and enhancement of risk of AEs in asthma patients.

The Oxidative Balance Score (OBS) is a new indicator of overall antioxidant/oxidant balance that provides a comprehensive picture of the body's overall oxidative stress status, with higher OBS indicating greater antioxidant exposure. A limited number of studies have examined the association between OBS and lung function and FeNO, and we aimed to investigate the possible relationship between OBS and lung function and FeNO.

Data utilized in this study were sourced from the 2007-2012 NHANES. Multivariable logistic regression was employed to investigate the association between OBS/lifestyle OBS (lifestyle antioxidants such as physical activity, etc., and lifestyle pro-oxidants such as alcohol, smoking, etc.)/dietary OBS (dietary antioxidants such as fiber, β-carotene, riboflavin, etc., and dietary pro-oxidants, such as total fat, etc.) and FEV1, FVC, PEF, FEF 25%- 75%, FeNO, as well as obstructive ventilation dysfunction. The dose-response association between the OBS and FEV1, FVC and PEF was explored using RCS analysis. Subgroup analysis and interaction tests were also conducted. We also used multivariable Cox regression modeling to explore the between OBS/lifestyle OBS/dietary OBS and all-cause and respiratory-related mortality.

A total of 8,568 participants were enrolled. A statistically significant association was observed between OBS/lifestyle OBS/dietary OBS and FEV1, FVC, and PEF levels. There was no statistical association between OBS, lifestyle OBS, dietary OBS, and FeNO levels. RCS revealed a linear relationship between OBS and both FEV1 and FVC levels. Notably, the positive correlation between OBS and dietary OBS with FEV1 was more significant in male participants. Conversely, the relationship between OBS and FVC levels was influenced by gender and BMI. The effects of the overall OBS, lifestyle OBS, and dietary OBS on lung function parameters were independent of whether participants had restrictive ventilatory dysfunction or obstructive ventilatory dysfunction.In addition, both the overall OBS and dietary OBS demonstrated significant inverse associations with all-cause mortality, whereas no statistically significant relationships were observed between these scores and respiratory-related mortality. Notably, only lifestyle OBS exhibited a significant inverse association with respiratory-related mortality.

In this study, OBS, lifestyle OBS, and dietary OBS levels were positively correlated with lung function parameters (FEV1, FVC and PEF) in U.S. adults. Exploring this association can enhance our understanding of how oxidative homeostasis influences lung function changes. This could provide valuable interventions for lung function decline. We also found that higher OBS was associated with lower all-cause mortality. Adopting a healthy lifestyle and consuming an antioxidant-rich diet may significantly improve the prognosis of patients by reducing oxidative stress-related damage.

This study aimed to investigate the effect of fractional exhaled nitric oxide (FeNO), a marker of airway inflammation, together with small airway function tests in diagnosing cough variant asthma (CVA), particularly in patients with gastroesophageal reflux disease (GERD).

This retrospective cohort study included adult patients with chronic cough for more than eight weeks who were divided into a CVA group and a control group. Participants underwent pulmonary function tests and FeNO measurements. Statistical tests and ROC curve analysis were used to assess diagnostic accuracy.

CVA patients had higher FeNO levels than controls, regardless of with or without GERD. There were no significant differences in FEV1, FVC, and FEV1/FVC ratio between the control and CVA groups, but CVA patients had significantly lower MEF25, MEF50, MEF75, and MMEF values. FeNO was negatively correlated with MEF50, MEF75, and MMEF. The AUC of FeNO in diagnosing CVA was 0.862. Combining FeNO with MMEF resulted in the highest diagnostic accuracy (AUC = 0.909). The diagnostic benefits of FeNO and FeNO + MMEF were similar in GERD patients.

Combining FeNO with small airway function tests, especially MMEF, can improve the diagnostic accuracy of CVA, while FeNO and FeNO + MMEF performed similar diagnostic accuracy in patients with GERD.

Not applicable.

The precise quantification of gaseous radicals in exhaled breath, such as fractional exhaled nitric oxide, serves as an invaluable noninvasive clinical diagnosis particularly in discerning various respiratory disorders. To date, the development of high-performance nitric oxide sensors compatible to modern electronic devices remains fundamentally challenging. We report that metal-organic frameworks (MOFs) with ligand spin immobilization demonstrate superior chemispintronic sensitivity and selectivity toward nitric oxide. Tetrathiafulvalene radical cations (TTF·+) within the MOF lattice considerably enhance the nitric oxide recognition via spin exchange interactions, leading to a five-order of magnitude reduction in the limit of detection (LOD), as compared to volatile organic compounds (VOCs) via carrier-doping mechanism. Record-low LOD of 0.12 parts per billion was achieved in M-TTF-spin (M = cobalt, zinc, and cadmium) MOFs, which also demonstrates exceptional selectivity over typical nitrogen oxides (NOx) and VOCs. This work opens up a distinct sensing platform for radical-like analytes through strategic design of spin-immobilized molecular functional motifs toward the spintronic device configurations.

Exposure-related changes in exhaled nitric oxide (FeNO) and sputum eosinophils have not been thoroughly compared in the investigation of occupational asthma.

This study aimed at comparing the accuracies of the changes in FeNO concentrations and sputum eosinophil counts in identifying asthmatic reactions induced by occupational agents during specific inhalation challenges (SICs).

This retrospective multicenter study included 321 subjects who completed an assessment of FeNO and sputum eosinophils before and 24 h after SICs with various occupational agents, of whom 156 showed a positive result.

Post-challenge changes in FeNO and sputum eosinophils showed similar accuracies, with areas under the receiver operating characteristics curve of 0.78 (95% confidence interval [95% CI], 0.72-0.83) and 0.81 (95% CI, 0.76-0.86), respectively. Increases in FeNO level ≥ 13 ppb and sputum eosinophils ≥ 1.25% were identified as the optimal threshold values for differentiating positive from negative SICs. Using these thresholds, the changes in FeNO and sputum eosinophils each achieved a ≥ 95% specificity but a low sensitivity (55% and 62%, respectively). FeNO and sputum eosinophils showed discordant increases in 38% of subjects with a positive SIC. Combining either a rise in FeNO ≥ 13 ppb or an increase in sputum eosinophils ≥ 1.25% increased the sensitivity to 77%.

Increases in FeNO concentration and/or sputum eosinophils after exposure to occupational agents strongly support a diagnosis of occupational asthma. The assessment of both markers of airway inflammation should be regarded as a reliable complementary tool to spirometry for identifying bronchial responses to occupational agents.

In this study, a non-invasive device based on ultraviolet differential absorption spectroscopy (UV-DOAS) technology for detecting fractional exhaled nitric oxide (FeNO)was developed and clinically validated in patients with various lung diseases. The diagnostic potential of FeNO was explored by analysing subgroups of patients with lung cancer, nodules, and other disease. The results showed that FeNO concentrations were significantly higher in patients with malignant tumours than in healthy controls (p < 0.01). The diagnostic efficacy of FeNO in different lung diseases was confirmed by ROC analysis: the AUC values were 0.925 for malignant tumours, 0.925 for suspected malignant/benign tumours, 0.792 for benign lesions, and 0.938 for infectious/inflammatory diseases. The significant postoperative FeNO level decrease supports the diagnostic use of FeNO in different stages of the disease. Compared with conventional electrochemical, chemiluminescent and fluorescent probe methods, the UV-DOAS technique has significant advantages regarding sensitivity and portability, suggesting its potential for clinical application.

The clinical and inflammatory characteristics of occupational asthma (OA) caused by persulfate salts (PS) in hair bleaches have not yet been comprehensively characterized.

This study aimed to compare the phenotypic characteristics of PS-induced OA with those of OA due to other low-molecular-weight (LMW) agents.

This study was conducted in a retrospective multicenter cohort of subjects with OA ascertained by a positive specific inhalation challenge (SIC). The clinical and inflammatory characteristics of hairdressers with PS-induced OA (n = 107) were compared with those of subjects who showed a positive SIC to isocyanates (n = 128) or various other LMW agents (n = 164).

Subjects with PS-induced OA had a longer duration of exposure to the offending agent before the onset of asthma than those with OA caused the other LMW agents. They reported more frequently work-related rhinitis (76%) and showed a lower post-SIC level of fractional exhaled nitric oxide (median, 18 ppb [25th-75th percentile, 13-26]) compared with OA caused by both isocyanates (36%, P < .001 and 35 ppb [21-80], P < .001, respectively) and the other LMW agents (53%, P < .001 and 27 ppb [14-52], P < .001). Subjects with PS-induced OA showed the highest rate of isolated late asthmatic reactions (49%), but the difference reached statistical significance only when compared with LMW agents other than isocyanates (31%, P < .002).

The PS-induced OA is associated with a higher prevalence of work-related rhinitis and lower levels of fractional exhaled nitric oxide compared with OA caused by other LMW agents. These findings further indicate substantial phenotypic heterogeneity among this broad category of agents.

The international and national guidelines for asthma management are typically comprehensive and designed for respiratory specialists, making them less practical for primary care physicians who handle most asthma cases. Recognizing the need for more accessible guidelines, the Japan Asthma Society developed the Practical Guidelines for Asthma Management (PGAM). PGAM aims to provide a concise summary of key asthma management principles, increasing awareness, education, and support among nonspecialists and patients alike. It includes user-friendly tables and lists outlining common symptoms, triggers, diagnostic criteria, and basic management strategies, along with frequently encountered treatable traits and comorbidities. These elements are presented through simple, clinically relevant algorithms. A notable feature of PGAM is the "Basic Roadmap for Asthma Management," which outlines a clear sequence for patient assessment, diagnosis, and treatment from initial consultation onward, offering an easy-to-follow visual guide. Additionally, the guidelines include methods for assessing airway inflammation, enabling patient phenotyping and endotyping. This supports a personalized treatment approach, particularly with biologics, aimed at achieving clinical remission.

Interstitial lung diseases (ILDs) are a group of pulmonary disorders characterized by fibrosis, inflammation, and lung tissue deterioration. Anti-melanoma differentiation-associated gene 5-positive dermatomyositis-associated interstitial lung disease (MDA5-ILD), a subtype, is associated with high mortality due to rapid progression and severe lung damage. Volatile organic compounds (VOCs) in exhaled breath, reflecting metabolic changes, have been identified as potential non-invasive biomarkers for various diseases, including respiratory conditions. However, their role in MDA5-ILD has not been extensively studied. This retrospective cohort study included 45 exhaled breath samples from 19 ILD patients, with 31 samples from 9 patients with MDA5-ILD and 10 samples from 7 patients with non-MDA5-ILD. VOCs were collected using thermal desorption tubes and analyzed via gas chromatography-mass spectrometry (GC-MS). Clinical data, including the APACHE II score, were integrated with VOC profiles. Two logistic regression models were developed: Model 1 based on 11 clinical indicators, and Model 2 integrating 11 clinical indicators with 5 VOC features. Model performance was evaluated using receiver operating characteristic (ROC) curve analysis, sensitivity, specificity, and accuracy metrics. Five VOCs-N-(2-Aziridinyl)ethanamine, Cyclohexanone, Nonanal, Dodecamethylcyclohexasiloxane, and 4-Methyltetradecane-were identified as significant biomarkers distinguishing MDA5-ILD from non-MDA5-ILD. Model 2, which integrated VOC data, outperformed Model 1, achieving an area under the curve (AUC) of 0.93 compared to 0.70. Model 2 also demonstrated enhanced accuracy (84.6% vs. 76.9%), specificity (66.7% vs. 33.3%), precision (90.0% vs. 81.8%), and F1-score (90.0% vs. 85.7%). Additionally, 1,3-Pentadiene and 3-Methylundecane were identified as potential markers of disease severity, with 1,3-Pentadiene negatively correlating and 3-Methylundecane positively correlating with both APACHE II scores and creatinine levels. VOCs in exhaled breath significantly enhance the diagnostic sensitivity and accuracy for detecting MDA5-ILD. In addition, VOCs show promise as disease severity markers, potentially aiding in the assessment of disease severity and progression. While the integration of VOCs holds great potential for improving diagnostic performance, further validation through larger, multicenter studies is necessary.

Background and objectives: Increased levels of nitric oxide (NO) are produced in various inflammatory diseases like allergic asthma. Fractional exhaled NO has been studied as a biomarker of type 2 inflammation in asthma, while the use of nasal NO (nNO) as a diagnostic tool for allergic rhinitis (AR) is less established. In the present study, we investigated nNO as a potential biomarker for differentiating AR from nonallergic rhinitis (NAR). Materials and methods: Medical students were invited to complete a questionnaire on rhinitis symptoms. Individuals who reported nasal symptoms were invited to participate in the clinical phase of the study, which included considering the patient's medical history, clinical examination, skin-prick tests (SPTs) for the 14 most relevant allergens in the region, and nNO measurement using the NIOX VERO portable nitric oxide analyzer. Informed consent was obtained at each stage of recruitment and clinical assessment. Results: Overall, 62 out of 122 volunteers recruited reported rhinitis symptoms and were investigated further with nNO measurements and SPTs. In total, 39 had SPT-confirmed AR, while 23 were classified as NAR subjects. Both nNO measurements and SPTs were performed on the same day, during the pollen season. The comparison of mean nNO concentrations (830 ± 247 ppb and 851 ± 373 in AR and NAR groups, respectively) showed no statistically significant difference. Conclusions: we concluded that nNO is not a reliable independent biomarker in the diagnosis of AR.

Treatable trait-based personalised medicine improves outcomes in severe asthma clinics. We assessed the feasibility of a randomised controlled trial (RCT) of protocolised treatable trait-guided asthma management in patients not under a severe asthma clinic.

Ten week single-group cohort study. Participants had a doctor's diagnosis of asthma, Asthma Control Questionnaire-5 (ACQ-5) score > 1, and ≥ 1 exacerbation in the last year.

biomarker-guided asthma medication according to a protocolised algorithm, targeting traits of type-2 inflammation and airflow obstruction. Feasibility outcomes: recruitment rates, acceptability of intervention, willingness to enrol in an RCT, need for 'extended' trait assessment after 10 weeks, and estimation of trait prevalence.

Recruitment ceased with 29/50 participants after 14 months due to difficulties associated with COVID-19. Recruitment rate: 29/118 (25%) of those invited to participate (95% CI 17 to 33). 24/26 (92%) participants found the intervention acceptable and were willing to participate in a future study. After 10 weeks, 65% remained not well controlled (ACQ-5 > 1) and would have required the 'extended' assessment. Participants had a mean (SD) 4.8 (2.3) of 13 traits assessed. ACQ-5 improved during the study by -1.0 (0.3 to 1.8) units, and post-bronchodilator airflow limitation reduced from 59% of participants to 35%. 12/29 (41%) participants received continuous oral corticosteroids at some point during the study.

Protocolised treatable trait management was acceptable to participants, associated with significant clinical benefit, and a full RCT appears feasible. Targeting type-2 inflammation and airflow obstruction was insufficient to control asthma in the majority of patients, despite marked systemic corticosteroid exposure.

ACTRN12620000935932.

Background: Early identification of septic patients in the ED is important, but high patient volumes and lengthy wait times often delay workups, and typically used noninvasive triage screening tools such as vital signs and qSOFA have poor sensitivity. Nitric oxide (NO) is a molecule in the blood that has been found to be upregulated in sepsis. Since it has a very short half-life in blood, its measurement can be challenging. We aimed to determine if exhaled NO could be used to help predict bacterial infection and sepsis. Methods: Emergency department patients with concern for infection were assessed for enrollment. Patients were included if blood cultures were ordered by the ED provider. The exhaled breath NO levels of enrolled subjects were measured. A score (vital signs and nitric oxide [VSNO]) was then created that included triage vital signs and NO level. Results: 104 patients (41 female) were enrolled. The median exhaled NO level was 9.8 parts per billion (ppb) (IQR: 5.6-17.0). Sixty-two (60%) patients were diagnosed with bacterial infection, and of those, 54 (52%) patients were diagnosed with sepsis. Using cut points of < 7 or > 12 ppb, the VSNO score demonstrated a sensitivity of 0.89 (95% CI: 0.77-0.96) and a specificity of 0.48 (95% CI: 0.34-0.63) for predicting sepsis. The score showed a sensitivity of 0.82 (95% CI: 0.70-0.91) and a specificity of 0.45 (95% CI: 0.30-0.64) for predicting bacterial infection. Conclusions: Exhaled NO measurement combined with vital signs has a high sensitivity for the detection of bacterial infection and sepsis. In a clinical setting, this score would be immediately available at the point of patient triage and would help to direct downstream evaluation and care. Further research is warranted.

Exhaled nitric oxide (FeNO) is a marker for airway inflammation measured by hand-held or stationary analyzers, but their usability was not previously assessed. NIOX VERO (CN), NObreath (BN), Vivatmo pro (BV), and CLD88 analyzer (reference, EC) were compared in a prospective study of the general population LEAD (Lung, hEart, sociAl, boDy) cohort, including the System Usability Scale and tests for equivalence at a clinically relevant range of ≤ 70 ppb with linear models and Bland-Altman plots. In 486 participants (62.4 ± 14.2 years old, 48.1% female), all hand-held analyzers had a good usability score, with BN scoring best. BV required the fewest attempts and time to measurement success, followed by BN. The FeNO results were clinically equivalent between devices (difference to EC 0.7-7.5 ppb) with increasing variability at higher FeNO values. The analyzers had an agreement of ≥ 95% at the threshold of ≥ 40 ppb. CN showed the lowest difference to EC, followed by BV. All portable analyzers showed good usability with an above-average usability score. The best usability score was observed with the BN device, while the BV device had the shortest measuring time and the fewest additional attempts. The lowest difference to the stationary EC analyzers was observed with the CN device.

Although the performance of dupilumab in severe asthma has been evaluated, the detailed mechanism underlying its effect remains unclear.

To analyze the effect of dupilumab on serum club cell secretory protein 16 (CC16).

A total of 25 patients who were administered dupilumab and underwent computed tomography before and approximately 4 months after the introduction of dupilumab were included. Clinical and computed tomography parameters before and after dupilumab administration, such as mucus plug score and wall area measurement, were compared along with serum CC16 levels. The correlation between the clinical background and treatment effects was also evaluated.

The number of mucus plugs and airway wall area decreased significantly after dupilumab introduction. The number of mucus plugs was positively correlated with both age and serum IgE levels. The number of mucus plugs and airway wall area was inversely correlated with percent of predicted forced expiratory volume in 1 second (FEV1) and maximal mid-expiratory flow. Dupilumab treatment resulted in a significant increase in serum CC16 levels and led to a significant improvement in asthma symptoms, quality-of-life scores, FEV1, and exacerbation frequency. In addition, changes in CC16 were significantly correlated with changes in the fraction of exhaled nitric oxide, IgE, quality-of-life score, FEV1, maximal mid-expiratory flow, and mucus plug score.

These data suggest that dupilumab improves symptoms and respiratory functions by altering the airway epithelial environment.

Background/Objective: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have a high morbidity of anosmia, yet there are few noninvasive biomarkers to measure treatment response. Nitric oxide (NO) is found in the paranasal sinuses at 100 times higher levels than in the lungs and is vital for antimicrobial and/or mucociliary activities and vasodilatory properties. Dupilumab has been shown to improve anosmia in 2 weeks as measured by the University of Pennsylvania Smell Identification Test (UPSIT), 22-item Sinonasal Outcome Test (SNOT-22), and Loss of Smell (LoS) scoring. We examined the use of NO in various collection methods to monitor anosmia improvement with dupilumab treatment. Methods: Adults with CRSwNP confirmed by computer tomography or endoscopy consented to receive dupilumab 300 mg every two weeks for 16 weeks. Subjects with polyposis despite treatment with steroids and/or a history of sinus surgery were recruited. Measurements of sinus NO (sNO) from the nostril while humming, nasal NO (nNO) while breath-holding, and fractional exhaled nitric oxide (FeNO) while exhaling were collected at baseline and at 1, 2, 4, 8, 12, 16 weeks. Olfactory impairment was measured by using the UPSIT, SNOT-22, and LoS scoring at every visit. Results: Sixteen adults, with a mean (range) age of 43 years (25-53 years) were predominantly women (12/16). Baseline mean (range) sNO values of 434 ppb (203-665 ppb) significantly increased at 2 weeks to a mean (range) of 1150 ppb (684-1616 ppb) (p < 0.05). Significant improvements in the UPSIT, SNOT-22, and LoS scores were found at 2 weeks; a weak correlation of the sNO level with the UPSIT and SNOT-22 scores was noted. No significant changes in the FeNO or nNO values were found. Significant improvement was found specifically with anosmia by the end of 2 weeks. Conclusion: Our small pilot study revealed increased sNO levels in the sinuses as early as 2 weeks after the initial dupilumab administration. Thus, in patients with CRSwNP without asthma, the sNO value has the potential to be used as a noninvasive, objective biomarker for early treatment improvement in anosmia.

Non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is a phenotype of bronchial asthma that is characterized by a severe course and the presence of chronic rhinosinusitis (CRS) with nasal polyps. MicroRNAs (miRNAs) belong to a family of small, non-coding RNAs whose primary function is to regulate gene transcription. The aim of this study was to determine the miRNA profile and to validate selected miRNAs in biological material from the upper respiratory tract collected with a minimally-invasive method in patients with N-ERD.

The miRNA profile was assessed in subjects with N-ERD, CRS, and allergic asthma (AA), as well as healthy controls (HCs), using microarray technique. Following this, 6 miRNAs were validated using reverse transcription polymerase chain reaction in 77 subjects.

The profiling identified 23 miRNAs whose expression significantly differed between patients with N-ERD and HCs. Based on these results, 6 miRNAs were selected for further validation. It was found that patients with N-ERD had significantly different expressions of miR-34a-5p and miR-22-5p compared to those with AA. In the whole study group, significant correlations were found between miR-7d-3p/miR-34a-5p/miR-22-5p and the presence of blood eosinophilia (r = 0.25, r = 0.28 and r = 0.26, for all P < 0.05). Forced expiratory volume in 1 second/forced vital capacity was correlated with miR-149a-5p expression (r = 0.27, P < 0.05).

The results indicate that the miRNA profile in nasal mucosal lining fluid of patients with N-ERD differs from patients with AA, CRS, and compared to HCs. Some of the miRNAs selected on the basis of profiling may be involved in the regulation of eosinophilic inflammation in the respiratory tract. Our findings suggest that specific miRNAs may be considered as potential biomarkers of N-ERD.

Nasal epithelial cells from young adults with a history of very preterm birth show delayed closure following scratch-wounding. Repair correlated with lung function, suggesting epithelial barrier integrity may play a role in preterm-associated lung disease. https://bit.ly/4dJnvWO.

Background: Allergy to Alternaria alternata (Alt a), although often underdiagnosed, is a significant global health issue. In the allergen immunotherapy (AIT) field, novel therapeutic strategies are emerging, particularly with the advent of polymerized allergoids. This study aims to evaluate the efficacy of subcutaneous immunotherapy (SCIT) based on these innovative molecules in children with respiratory allergies, assessing clinical and functional parameters. Methods: We enrolled 42 patients aged between 6 and 16 years, all of whom had allergic rhinitis (AR) and concomitant asthma and all of whom were monosensitized to Alt a. Between December 2020 and December 2021, 17 patients initiated SCIT with Modigoid® for Alt a1, while 25 patients continued with standard therapy. At the initial visit (T0), all the patients underwent nasal and bronchial evaluation, including exhaled nitric oxide (eFeNO) measurement and spirometry. The Asthma Control Test (ACT) was used to evaluate the control of asthma symptoms. Patients were followed up every 6 months, with a comprehensive re-evaluation at 24 months (T1) replicating the initial assessments. Results: After 24 months of SCIT with the new polymerized molecular allergoid Alt a1 (Modigoid®), children showed a statistically significant reduction in eFeNO levels, improved FEV1 values, and enhanced ACT scores. Conclusions: SCIT with the new molecular allergoid Alt a1 significantly improves functional parameters (FEV1 and eFeNO) and subjective asthma symptoms (ACT scores) in children with AR and objective asthma signs. This treatment represents an effective preventive strategy that can be used to halt the progression of the classic atopic march from AR to asthma and potentially reverse the atopic march.

Background: Emerging evidence suggests that nutraceuticals, alongside standard therapy, may benefit children with allergic rhinitis (AR). This study aimed to compare the efficacy of Quertal® (Neopharmed Gentili S.p.A., Milano, Italy), a nutraceutical supplement based on Perilla frutescens, Quercetin, and vitamin D3, combined antihistamines per os versus antihistamines alone, in improving AR symptoms considering respiratory functional and laboratory biomarkers in pediatric age. Materials and Method: This study included 100 children, 50 in the case group (Quertal® plus antihistamines) and 50 in the control group (antihistamines alone), with mild/moderate AR sensitized to grass pollens. They underwent assessments of respiratory function (rhinomanometry-AAR, spirometry), inflammation markers (Nasal Nitric Oxide [nFeNO]; exhaled Nitric Oxide [eFeNO]; nasal cytology), and laboratory assays (blood eosinophils, total IgE and specific IgE to Phl p1). Results: After three months of treatment, the case group showed statistically significant improvement in nFeNO and eFeNO values compared to controls (p < 0.001), as well as a reduction in nasal eosinophils (p < 0.001). Conclusions: Adding Quertal® to standard antihistamine therapy may reduce nasal inflammation and improve AR symptoms in pediatric patients. This combination therapy shows promise as a practical, well-tolerated approach to managing AR and may have broader implications for enhancing long-term outcomes.

Type 2 inflammation in the airways and lungs is inflammation induced by type 2 cytokines such as IL-4, IL-5, and IL-13, produced primarily by type 2 helper T cells and type 2 innate lymphoid cells, and causes changes in the physiology and structure of the airways. Type 2 inflammation is currently in the spotlight because of its direct link to the treatment of several airway and lung diseases. Abundant evidences have accumulated that inflammatory biomarkers such as blood eosinophils, fractional exhaled nitric oxide, and IgE are essential clinical tools in the diagnosis and management of asthma and COPD. It is well known that asthma and COPD have diverse inflammatory phenotypes even when clinical features are similar, and it has been demonstrated that assessment of airway inflammation with biomarkers can improve diagnostic accuracy, determine safer and more effective treatment strategies, and predict future risks such as exacerbations and lung function decline. The Japanese Respiratory Society has published clinical practice guidelines for the evaluation of type 2 inflammation in the airways and lungs. In addition to asthma and COPD, the guide covers a wide range of airway and lung diseases, including interstitial lung disease, allergic bronchopulmonary mycosis, allergic rhinitis, and eosinophilic chronic rhinosinusitis. It also provides comprehensive guidelines covering a variety of clinical biomarkers. The purpose of this guidance is to provide evidences for the interpretation of type 2 inflammation measurements and to promote the widespread use of inflammation assessment to further improve the efficiency of airway and respiratory disease management.

Asthma is a major public health challenge in China. Although chest pain variant asthma (CPVA) is not common in clinical practice, there are still a few people who only or mainly manifest as chest pain. Here, we aim to introduce the characteristics of their symptoms, lung function and chest imaging features to arouse the attention of physicians to know better of the disease.

We retrospectively analyzed thirty-one patients who had been diagnosed with CPVA based on clinical data and positive bronchial provocation tests (BPTs).

The mean age of all enrolled patients was forty-seven years, and females accounted for 64.5%. Main features of chest pain manifested as dull pain and mild pain with unfixed location, and several patients were presented with distending pain, pinprick pain, chest pain related to breathing, chest pain position-related and chest pain like angina pectoris. The median duration of their chest pain was four months, and 77.4% of the patients did not find any trigger. Among the 31 patients, 10 were with normal lung function, 14 were with mild obstructive ventilation dysfunction, 6 were with small airway dysfunction and 1 was with mild restrictive ventilation dysfunction. The predicted values of forced expiratory volume in 1 s (FEV1) were greater than 80% in 29 out of 31 patients, and the values of other two patients were 74% and 79%, respectively. Additionally, 35.5% of the patients meanwhile had allergic rhinitis, and 64.5% of the patients exhibited type 2 inflammation. Among the 31 patients, 22 (71.0%) showed abnormalities on inspiratory computed tomography (CT) scans, including bronchiolar (38.7%), bronchial (25.8%) or pulmonary parenchyma abnormalities (32.3%). Only 7 patients (22.6%) had normal inspiratory CT scans.

CPVA is relatively rare in clinical practice. Understanding its manifestations, lung function, chest CT features and comorbidities is helpful for diagnosis and evaluation of patients with such symptoms.

This study aimed to assess the acute effects of two isoenergetic but micronutrient-diverse meals-a Mediterranean-like meal (MdM) and a fast food-like meal (FFM)-on the autonomic nervous system (ANS), lung function, and airway inflammation response.

Forty-six participants were enrolled in a randomized crossover clinical trial, consuming two isoenergetic meals: FFM (burger, fries, and sugar-sweetened drink) and MdM (vegetable soup, whole-wheat pasta, salad, olive oil, sardines, fruit, and water). Pupillometry assessed parasympathetic (MaxD, MinD, Con, ACV, MCV) and sympathetic (ADV, T75) nervous system outcomes. Lung function and airway inflammation were measured before and after each meal through spirometry and fractional exhaled nitric oxide (FeNO), respectively.

Mixed-effects model analysis showed that the MdM was associated with a hegemony of parasympathetic responses, with a significant increase of MaxD associated with a faster constriction velocity (ACV and MCV); on the other side, the FFM was associated with changes in the sympathetic response, showing a quicker redilation velocity (a decrease in T75). After adjusting for confounders, the mixed-effects models revealed that the FFM significantly decreased T75. Regarding lung function, a meal negatively impacted FVC (ae = -0.079, p < 0.001) and FEV1 (ae = -0.04, p = 0.017); however, FeNO increased, although after adjusting, no difference between meals was seen.

Our study showed that the FFM counteracted the parasympathetic activity of a meal, while a meal, irrespective of the type, decreased lung function and increased airway inflammation.

The significance of measuring Fractional Exhaled Nitric Oxide (FeNO) has grown, particularly in monitoring respiratory diseases like asthma. FeNO levels indicate inflammation and a rise in response to respiratory irritants. This study investigates whether repeated exposure to irritants in metal casting and coating leads to respiratory inflammation and assesses the benefits of including FeNO measurement in periodic occupational health screenings.

This cross-sectional study involved 99 workers aged 18-65 in the foundry and metal coating sectors in the İkitelli Organized Industrial Zone. The study group included 54 workers exposed to metal dust and fumes, while the control group comprised 45 workers in non-exposure roles (e.g., secretarial, assembly, packaging). Data were collected through face-to-face interviews, recording demographics, smoking habits, symptoms. FeNO levels were measured and analyzed with pulmonary function test parameters.

FeNO levels were significantly higher in the study group compared to the control group (p = 0.02). No significant relationships were found between FeNO levels and age, height, weight, BMI, waist circumference, years of work, or symptom presence, but a significant negative correlation was observed between FeNO levels and FEV1/FVC. Additionally, current smokers had significantly lower FeNO levels compared to those who had quit or never smoked (study, p = 0.014; control, p = 0.011).

Monitoring FeNO levels in occupational health assessments may facilitate early intervention and preventive measures, protecting worker health. Incorporating FeNO measurement into periodic screenings could enhance occupational health practices.

Particulate matter exposure has been linked to impaired respiratory health in children, but the respiratory benefits of air purification have not been fully elucidated.

To assess the respiratory health outcomes among children exposed to multisetting air purification vs sham purification.

This cluster randomized, double-blind, crossover trial was conducted among healthy school-aged children (10-12 years) in China from April to December 2021. Data were analyzed from December 2021 to July 2024.

A multisetting (both in classrooms and bedrooms) air purification intervention compared with sham purification in a 2-stage intervention with more than 2 months (76 days) for each period and a washout period (88 days) to estimate the respiratory benefits of air purification.

The primary outcomes were pulmonary function, airway inflammation markers, and metabolites in exhaled breath condensate (EBC) before and after the air purification intervention. Linear mixed-effects models were used to estimate the respiratory benefits of children related to air purification. Differential metabolites in EBC were identified using metabolomics analysis to explore their possible mediation roles.

A total of 79 children (38 male [48%]; mean [SD] age, 10.3 [0.5] years) were included in the statistical analyses. During the study period, the mean (SD) concentration of outdoor fine particulate matter (PM2.5) at the school site was 32.53 (24.06) μg/m3. The time-weighted personal PM2.5 concentration decreased by 45.14% during the true air purification period (mean [SD], 21.49 [8.72] μg/m3) compared with the sham air purification period (mean [SD], 39.17 [14.25] μg/m3). Air purification improved forced expiratory volume in 1 second by 8.04% (95% CI, 2.15%-13.93%), peak expiratory flow by 16.52% (95% CI, 2.76%-30.28%), forced vital capacity (FVC) by 5.73% (95% CI, 0.48%-10.98%), forced expiratory flow at 25% to 75% of FVC by 17.22% (95% CI, 3.78%-30.67%), maximal expiratory flow at 75% of FVC by 14.60% (95% CI, 0.35%-28.85%), maximal expiratory flow at 50% of FVC by 17.86% (95% CI, 3.65%-32.06%), and maximal expiratory flow at 25% of FVC by 18.22% (95% CI, 1.73%-34.70%). Fractional exhaled nitric oxide in the true air purification group decreased by 22.38% (95% CI, 2.27%-42.48%). Several metabolites in EBC (eg, L-tyrosine and β-alanine) were identified to mediate the effect of air purification on respiratory health.

This randomized clinical trial provides robust and holistic evidence that indoor air purification notably improved pulmonary health in children, highlighting the importance of intensified indoor air purification in regions with high air pollution levels.

ClinicalTrials.gov Identifier: NCT04835337.

Prolonged or recurrent cough is a common reason for referral to pediatric pulmonologists, yet few studies have assessed its causes. We examined records of children visiting respiratory outpatient clinics in Switzerland and assessed how diagnoses vary by age.

We analyzed data from the multicenter Swiss Paediatric Airway Cohort study. We included 363 children (median age 6 years, range 0-16) referred for prolonged or recurrent cough. From outpatient records, we extracted information on diagnostic investigations, final diagnoses proposed by pediatric pulmonologists, and treatments prescribed.

Asthma and asthma-like conditions (cough variant asthma, episodic viral wheeze, and recurrent obstructive bronchitis) were diagnosed in 132 (36%) of 363 children, respiratory tract infections (RTI) including protracted bacterial bronchitis (PBB) in 51 (14%), upper airway cough syndrome (UACS) in 48 (13%), and postinfectious cough in 36 (10%); other diagnoses including gastroesophageal reflux disease (GERD) and somatic cough syndrome or tic cough were found in 23 (6%). No etiology was found in 73 children (20%). Asthma was diagnosed 3.5 times more often in schoolchildren while RTI including PBB was diagnosed three times more often in preschoolers. Inhaled corticosteroids were prescribed for 84% of children diagnosed with asthma and asthma-like conditions, antibiotics for 43% of children with RTI, and nasal corticosteroids for 83% of those with UACS.

Coughing children received a wide spectrum of diagnoses that differed between preschool and schoolchildren. Asthma accounted for 36% of diagnoses, which emphasizes the importance of comprehensive investigation beyond asthma in children with prolonged or recurrent cough.

To evaluate the effect of short-term inhalational exposure to nanoparticles released during dental composite grinding on oxidative stress and antioxidant capacity markers.

Twenty-four healthy volunteers were examined before and after exposure in dental workshop. They spent 76.8 ± 0.7 min in the testing room during grinding of dental nanocomposites. The individual exposure to aerosol particles in each participant´s breathing zones was monitored using a personal nanoparticle sampler (PENS). Exhaled breath condensate (EBC), blood, and urine samples were collected pre- and post-exposure to measure one oxidative stress marker, i.e., thiobarbituric acid reactive substances (TBARS), and two biomarkers of antioxidant capacity, i.e., ferric-reducing antioxidant power (FRAP) and reduced glutathione (GSH) by spectrophotometry. Spirometry and fractional exhaled nitric oxide (FeNO) were used to evaluate the effect of acute inhalational exposure.

Mean mass of dental nanocomposite ground away was 0.88 ± 0.32 g. Average individual doses of respirable particles and nanoparticles measured by PENS were 380 ± 150 and 3.3 ± 1.3 μg, respectively. No significant increase of the post-exposure oxidative stress marker TBARS in EBC and plasma was seen. No decrease in antioxidant capacity biomarkers FRAP and GSH in EBC post-exposure was seen, either. Post-exposure, conjunctival hyperemia was seen in 62.5% volunteers; however, no impairment in spirometry or FeNO results was observed. No correlation of any biomarker measured with individual exposure was found, however, several correlations with interfering factors (age, body mass index, hypertension, dyslipidemia, and environmental pollution parameters) were seen.

This study, using oxidative stress biomarker and antioxidant capacity biomarkers in biological fluids of volunteers during the grinding of dental nanocomposites did not prove a negative effect of this intense short-term exposure. However, further studies are needed to evaluate oxidative stress in long-term exposure of both stomatologists and patients and diverse populations with varying health statuses.

The forced oscillation technique (FOT) is a minimally invasive test to evaluate asthma during resting ventilation. However, its role in longitudinal assessments, such as clinical remission, remains unclear.

To longitudinally assess asthma clinical remission and identify parameters that predict clinical remission at 12 months from baseline FOT.

Adult patients with asthma at our university hospital between April 2022 and May 2023 were enrolled in this prospective observational study. They were evaluated for 12 months after enrollment to determine whether they met the following clinical remission criteria: asthma control test score of more than or equal to 20 at enrollment and 12 months, no asthma exacerbations for 12 months, and no regular oral corticosteroid use during the 12 months. FOT parameters at enrollment were analyzed for associations with clinical remission.

A total of 94 patients with asthma completed the study and were categorized into clinical and nonclinical remission groups. Comparison of pulmonary function tests, including the FOT, between the 2 groups revealed significant differences in resistance at 5 Hz and resistance at 20 Hz (R20) but not in forced expiratory volume in 1 second. Multivariate logistic regression analysis revealed that R20 was associated with clinical remission, with adjusted odds ratios of 0.32 (95% CI: 0.12-0.91, P = .033) for R20.

R20 can be a useful predictor of future exacerbations in patients with asthma. These findings may assist in evaluating adult patients with asthma and normal forced expiratory volume in 1 second.

Despite the availability of numerous guidelines for asthma management, their recommendations are not consistently implemented in clinical practice. This discrepancy between guidelines and real-world practice among Italian healthcare professionals was explored during the "Revolution in Asthma" training program, which identified "gray areas" and barriers preventing clinicians from adopting guideline-based approaches.

This study aims to analyze the key challenges in asthma management and provide evidence-based solutions to improve adherence to guidelines in clinical practice.

A group of experts from the Scientific Committee of the Revolution in Asthma project reviewed the program's findings, focusing on three main areas of asthma management: diagnosis, control, and treatment. The experts summarized clinicians' main needs and questions for each area and provided evidence-based responses and practical recommendations.

The study highlights critical challenges in asthma treatment, addressing two key questions: (a) What are the possible uses and indications for short-acting β-agonists in asthma patients? (b) How should asthma treatment be initiated and adjusted based on asthma control? The expert panel developed practical, operational tools to support general practitioners and specialists (pulmonologists and allergists) in optimizing asthma management.

This paper serves as a knowledge co-creation initiative, bridging the gap between clinical guidelines and daily practice. By offering concrete recommendations, it aims to enhance the application of guideline-based asthma management among healthcare professionals.

Global Initiative for Asthma (GINA) recently recommends clinicians to reduce inhaled corticosteroid doses in patients with severe asthma who respond positively to monoclonal antibodies (MAbs).

As we operated this reduction even before the document, we analysed our cohort of subjects on treatment with a MAbs for at least 24 months.

Data stored in our electronic archive and at the 6-month follow-up (FU) were registered and patients' adherence to asthma therapy was derived by electronic pharmacy claim database.

Sixty-three subjects were enrolled. A complete asthma remission and reduction to GINA Step 3 was obtained in 41 % and 61 % of them, respectively. Non-adherent subjects to inhaled and oral asthma therapy were 45 % of them, with a higher percentage among those in complete remission (59 % vs 33 %).

In our cohort, stepping down asthma therapy from 5 to 3 level in severe asthmatic patients on Mabs is without any negative consequences on asthma control, even in the case of non-adherence.

Sarcoidosis is considered a T-helper (Th) 1 related disease, but a transition from Th1 to Th2 pathway activation has been postulated in sarcoidosis-associated pulmonary fibrosis (SAPF). Fraction of exhaled nitric oxide (FENO) is a marker of Th2 airway inflammation, but alveolar concentration of nitric oxide (CANO) can be measured to assess Th2 inflammation in the periphery of the lung. The aim of this study is to assess whether CANO can be considered a biomarker of SAPF or active pulmonary sarcoidosis. In this single-center retrospective study, we compared exhaled NO levels of patients with pulmonary sarcoidosis without fibrosis (N= 11) with those obtained from patients with SAPF (N= 15). Clinical data, as well as respiratory function tests, were also analyzed. FENO (28.5 ± 16 ppb vs 30.9 ± 17.2 ppb,p= 0.72) and CANO (4.4 ± 3.5 ppb vs 3.2 ± 1.7 ppb,p= 0.73) levels did not differ significantly between patients with or without SAPF, even when dividing them according to treatment or disease activity. CANO appeared reduced in patients with active sarcoidosis (2.1 ± 0.8 ppb vs 4.1 ± 3 ppb,p< 0.05). In conclusion, CANO cannot be considered a biomarker of SAPF. Its lower level in patients with active disease confirms the prevalence of Th1 inflammation in granuloma formation and suggests its potential role as a biomarker of active pulmonary sarcoidosis, but further studies with larger samples are needed to confirm this hypothesis.

The concentrations of nasal nitric oxide (nNO) vary in patients with chronic rhinosinusitis (CRS) supposedly depending upon whether the paranasal ostia are open or obstructed. Our aim was to assess whether nNO levels and their response to topical xylometazoline (a local vasoconstrictor used to alleviate nasal congestion) in patients with CRS differ between those with open or obstructed ostia and if the results were altered by the use of nasal corticosteroids. Sixty-six patients with CRS (43% with nasal polyps) or recurrent acute rhinosinusitis and 23 healthy controls were included. Nasal NO was measured (EcoMedics CLD 88p analyser) before and after two xylometazoline sprays during three consecutive visits: with the medication they were using when they were referred, after 4 weeks of medication pause, and after 4 weeks of using intranasal fluticasone propionate. The relative difference between the nNO before and after dosing of xylometazoline was calculated, and ostial obstruction was evaluated with cone-beam computed tomography at every visit. The nNO measurements were lowest in the patients with CRS and obstructed paranasal ostia. The presence or absence of nasal polyps did not affect the results. Xylometazoline did not significantly affect nNO in the subjects with obstructed ostia, but there was a significant reduction of nNO in those with open ostia. The Xylometazoline-induced change in nNO between the groups with open or obstructed ostia was significantly different at each visit: 'on previous medication' 10% (-5-25) versus -14% (-19 to -9),p= 0.004, 'after medication pause' 6% (-5-17) versus -16% (-23 to -9),p= 0.001 and 'after regular fluticasone spray' 6% (-3-15) versus -9% (-16 to -3),p= 0.04. The native nNO and xylometazoline-induced change in nNO can be used to detect the status of ostial obstruction in patients with CRS irrespective of their topical corticosteroid usage.

It remains unclear whether baseline FeNO levels can predict response to anti-IL5/5R biologic treatment in patients with severe asthma.

We recruited 104 patients with severe eosinophilic asthma treated with anti-IL5/anti-IL5R for at least one year who had measured FeNO values before the beginning of anti-eosinophilic treatment. Population was divided into subjects with FeNO < 25 and ≥25 ppb. In each group we evaluated the changes in pulmonary function (FEV1% and FEF25-75%), clinical (ACT and exacerbations) and steroid-sparing effect, expressed as the modification of daily dosage of inhaled corticosteroids (ICS) and oral corticosteroids (OC), after anti-IL5/anti-IL5R.

FEV1 changes after treatment were 3.34 ± 15,97% in subjects with low baseline FeNO, whereas 11.2 ± 16.1% in individuals with FeNO ≥ 25 ppb (p = 0.012). Also, FEF25-75% variations after treatment were different in the two groups: 2.1 ± 10.7% vs 9.6 ± 18% in individuals with FeNO < 25 and ≥25 respectively (p = 0.05). Conversely, ACT (4.4 ± 4.2 vs 5.9 ± 4.6; p = 0.147), exacerbation changes (-2.46 ± 1.5 vs -2.9 ± 1.6; p = 0.137) after treatment were similar in both groups where ICS dosages reduction was alike. On the contrary, the percentage of subjects that reduced/stopped OC treatment after anti-IL5/anti-IL5R was 71.7% in the group with FeNO < 25 ppb whereas 94.1% in individuals with FeNO ≥ 25 (p = 0.06). Multivariate analysis adjusted for all confounding factors also confirmed the relationship between FeNO ≥ 25 and improvement in FEV1%/FEF25-75% (β = 8.372, p = 0.013 and β = 8.883; p = 0.062 respectively) and the increased probability of discontinuing/reducing OC use (OR:17.838 [95%CI:3.159-100.730]; p = 0.001) in the high FeNO group.

Pre-biologic FeNO might predict a greater response to treatment with anti-IL-5/5R especially in terms of lung function and OC sparing in subjects with severe eosinophilic/allergic asthma. This could likely be a biomarker that can better guide in choosing an anti-IL5/5R in severe overlapping asthma (eosinophilic/allergic) to maximize treatment effects.

Indoor environment and health have drawn public attention worldwide. However, the joint health effects and mechanisms of exposure to different types of indoor environmental factors remain unclear. We established an exploratory panel study on indoor environment and health effects among young adults in China (the China IEHE Study) to comprehensively investigate 3M issues, including multiple indoor environmental factors, multiple health effects, and multiple omics methods for mechanism exploration. This protocol aims to systematically introduce the entire China IEHE Study. Eighty-one young adults aged 18-28 years from a university adjacent to traffic arteries in Beijing were recruited and followed up four times. Sham/real air purification intervention was simultaneously applied in a randomized crossover order. A broad range of indoor physical, chemical, and biological factors were characterized through real-time monitoring and external and internal exposure analyses. Subclinical health indices reflecting cardiopulmonary, sleep, and cognitive health were repeatedly measured in a prospective order. Various biosamples including fasting venous blood, morning urine, nasal mucosal lining fluid, and exhaled breath condensate were collected to explore the underlying biological mechanisms. The China IEHE Study comes up with an enlightening framework for future prospective studies associated with the exploration of multisystem health effects and underlying biological mechanisms of indoor exposure.

Most physiological production of Fractional exhaled Nitric Oxide (FeNO) occurs in the small airways, but studies on the relationship between FeNO and small airway dysfunction (SAD) in asthma are scant.

To investigate the relationship between asthma control, changes of FeNO in relation to airway bronchodilation (BD), and SAD.

Baseline conventional spirometry, impulse oscillometry, and FeNO pre- and post-BD (salbutamol 400 μg) were tested on consecutive community-treated adult patients with asthma. Results were stratified by FeNO response (change in FeNO [ΔFeNO]), being FeNO "responder" if the increase is greater than 10% post-BD compared with the basal values and "nonresponder" if less than or equal to 10%.

When measured, post-BD FeNO greater than 25 parts per billion was found in an additional 31.5% of patients. Of the 92 patients included, 61% were classified as FeNO "responders" and 39% as "nonresponders." A significant moderate-to-strong correlation was observed between ΔFeNO and R5R20, a functional marker of SAD (R = 0.52, P < .0001), whereas the correlations between spirometry markers and ΔFeNO were not significant (P > .05). Both R5R20 and ΔFeNO inversely correlated with asthma control (P < .0001). Using causal mediation analysis modeling, the effect of asthma control on ΔFeNO was mediated by SAD, with a strong indirect effect of asthma control on ΔFeNO mediated by SAD (β value: -7.04, 95% CI: -11.80 to -3.53, P < .0001), without a significant direct effect (β value: -4.96, 95% CI: -9.15 to 0.11, P = .056).

Changes in FeNO values pre-/post-BD can improve the identification of patients with "TH2 high" asthma. The relationship between ΔFeNO and asthma control is mainly mediated by SAD, highlighting its contribution to asthma control.

Air purifiers can enhance indoor air quality and health outcomes, and studies have primarily focused on filters and particulate matter (PM) in households. Photocatalytic oxidation (PCO) is a promising technique for eliminating gaseous pollutants and bioaerosols. However, no field study was conducted in household. Therefore, this study evaluated the effects of the PCO and PCO + filters intervention on indoor air pollutants and cardiopulmonary endpoints in households.

A randomized, double-blind crossover clinical trial was conducted. Indoor air pollutants, including PM, bioaerosols, and gaseous pollutants and cardiopulmonary endpoints including lung function, fractional exhaled nitric oxide (FeNO), respiratory symptoms, and blood pressure were assessed before and after intervention.

This was the first study to evaluate the effects of PCO and PCO + filters interventions on indoor air pollutants and cardiopulmonary health in households. Indoor total volatile organic compounds (TVOC) and sulfur dioxides (SO2) significantly reduced after PCO intervention, however, we also observed the significant reduction in percentage of predicted values of forced vital capacity (FVC%) and forced expiratory volume in 3 s (FEV3%) and increased in FeNO after 13 days of PCO intervention. The PCO + filters intervention significantly reduced the levels of indoor PM1, PM2.5, PM4, PM10, total suspended particulate matter, ultrafine particles, airborne bacteria, fungi, endotoxin, mites, TVOC, nitrogen dioxide, and SO2, and marginal reduction in carbon monoxide. However, indoor carbon dioxide significantly increased after PCO/PCO + filters intervention. As for cardiopulmonary health, FVC%, and FEV1 % marginally increased 7 days after the PCO + filters intervention.