Device comparison study to measure nasal nitric oxide in relation to primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a genetic respiratory disease characterized by chronic cough, recurrent respiratory infections, and rhinosinusitis. The measurement of nasal nitric oxide (nNO) against resistance has been suggested as a sensitive screening method. However, current recommendations argue for the use of expensive, chemiluminescence devices to measure nNO. This study aimed to compare nNO measurement using three different devices in distinguishing PCD patients from healthy controls and cystic fibrosis (CF) patients and to evaluate their diagnostic precision. The study included 16 controls, 16 PCD patients, and 12 CF patients matched for age and sex. nNO measurements were performed using a chemiluminescence device (Eco Medics CLD 88sp), and two devices based on electrochemical sensors (Medisoft FeNO+ and NIOX Vero) following standardized guidelines. Correlation estimation, Bland-Altman, ROC curve, and one-way ANOVA were used to assess device differences and diagnostic performance. Significantly lower nNO output values were observed in PCD and CF patients compared to controls during exhalation against resistance. The correlation analysis showed high agreement among the three devices. ROC curve analysis demonstrated 100% sensitivity and specificity at different cut-off values for all devices in distinguishing PCD patients from controls (optimal cut-offs: EcoMedics 73, Medisoft 92 and NIOX 87 (nl min-1)). Higher nNO output values were obtained with the Medisoft and NIOX devices as compared to the EcoMedics device, with a bias of-19 nl min-1(95% CI: -73-35) and -21 nl min-1(-73-31) accordingly. These findings indicate that all three tested devices can potentially serve as diagnostic tools for PCD if device specific cut-off values are used. This last-mentioned aspect warrants further studies and consideration in defining optimal cut-offs for individual device.

Persistent Aspergillus fumigatus infection in cystic fibrosis: impact on lung function and role of treatment of asymptomatic colonization-a registry-based case-control study.

BACKGROUND: Aspergillus fumigatus is the most common filamentous fungus isolated from the airways of people with cystic fibrosis (CF). The aim of this study was to investigate how chronic A. fumigatus colonization affects lung function in people with CF, to identify risk factors for colonization, and to evaluate antifungal treatment of asymptomatic Aspergillus colonization. METHODS: Data from 2014-2018 was collected from the Swedish CF registry and medical records. Baseline data before the start of A. fumigatus colonization was compared with the two succeeding years to evaluate how colonization and treatment affected lung function and other clinical aspects. RESULTS: A total of 437 patients were included, of which 64 (14.6%) became colonized with A. fumigatus during the study period. Inhaled antibiotics was associated with A. fumigatus colonization (adjusted OR 3.1, 95% CI 1.6-5.9, p < 0.05). Fungal colonization was not associated with a more rapid lung function decline or increased use of IV-antibiotics compared to the non-colonized group, but patients with A. fumigatus had more hospital days, a higher increase of total IgE, and higher eosinophil counts. In the Aspergillus group, 42 patients were considered to be asymptomatic. Of these, 19 patients received antifungal treatment. Over the follow up period, the treated group had a more pronounced decrease in percent predicted Forced Expiratory Volume in one second (ppFEV1) compared to untreated patients (- 8.7 vs - 1.4 percentage points, p < 0.05). CONCLUSION: Inhaled antibiotics was associated with A. fumigatus colonization, but no association was found between persistent A. fumigatus and subsequent lung function decline. No obvious benefits of treating asymptomatic A. fumigatus colonization were demonstrated.

Cross-sectional study on exhaled nitric oxide in relation to upper airway inflammatory disorders with regard to asthma and perennial sensitization.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is a well-known marker of type-2 inflammation. FeNO is elevated in asthma and allergic rhinitis, with IgE sensitization as a major determinant. OBJECTIVE: We aimed to see whether there was an independent association between upper airway inflammatory disorders (UAID) and FeNO, after adjustment for asthma and sensitization, in a multi-centre population-based study. METHODS: A total of 741 subjects with current asthma and 4155 non-asthmatic subjects participating in the second follow-up of the European Community Respiratory Health Survey (ECRHS III) underwent FeNO measurements. Sensitization status was based on measurement of IgE against airborne allergens; information on asthma, UAID and medication was collected through interview-led questionnaires. Independent associations between UAID and FeNO were assessed in adjusted multivariate regression models and test for interaction with perennial sensitization and asthma on the relation between UAID and FeNO were made. RESULTS: UAID were associated with higher FeNO after adjusting for perennial sensitization, asthma and other confounders: with 4.4 (0.9-7.9) % higher FeNO in relation to current rhinitis and 4.8 (0.7-9.2) % higher FeNO in relation to rhinoconjunctivitis. A significant interaction with perennial sensitization was found in the relationship between current rhinitis and FeNO (p = .03) and between rhinoconjunctivitis and FeNO (p = .03). After stratification by asthma and perennial sensitization, the association between current rhinitis and FeNO remained in non-asthmatic subjects with perennial sensitization, with 12.1 (0.2-25.5) % higher FeNO in subjects with current rhinitis than in those without. CONCLUSIONS & CLINICAL RELEVANCE: Current rhinitis and rhinoconjunctivitis was associated with higher FeNO, with an interaction with perennial sensitization. This further highlights the concept of united airway disease, with correlations between symptoms and inflammation in the upper and lower airways and that sensitization needs to be accounted for in the relation between FeNO and rhinitis.

Exhaled and nasal nitric oxide in relation to lung function, blood cell counts and disease characteristics in cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis (CF) have similar or lower exhaled nitric oxide (FeNO) and lower nasal nitric oxide (nNO) levels than controls. There are divergent results on alveolar NO (CalvNO) concentrations in relation to CF. There are inconsistent results on correlation between different nitric oxide parameters and lung function and inflammation in CF. AIM: To compare FeNO, CalvNO and nNO levels between subjects with CF, asthma and healthy controls and to study whether these parameters are related to lung function, blood cell counts or clinical characteristics in CF patients. MATERIAL AND METHODS: Measurements of FeNO at multiple exhalation flow rates, nNO and spirometry were done in 38 patients (18 adults) with CF. Blood cell counts and CF clinical characteristics were recorded. Thirty-eight healthy controls and 38 asthma patients, gender- and age-matched, were included as reference groups. RESULTS: FeNO levels were lower in CF patients (7.2 [4.7-11.2] ppb) than in healthy controls (11.4 [8.3-14.6] ppb) and asthma patients (14.7 [8.7-24.7] ppb) (both p < 0.005). These differences were consistent in adults. No difference in CalvNO was seen between the groups. nNO levels in CF patients (319 [193-447] ppb) were lower than in healthy controls (797 [664-984] ppb) and asthma patients (780 [619-961] ppb) (both p < 0.001). FeNO positively related to FEV1 (rho = 0.51, p = 0.001) in CF patients and this was consistent in both adults and children. A negative correlation was found between FeNO and blood neutrophil counts (rho = -0.37, p = 0.03) in CF patients. CONCLUSION: CF patients have lower FeNO and nNO and similar CalvNO levels as healthy controls and asthma patients. Lower FeNO related to lower lung function in both adults and children with CF. Furthermore, in CF, lower FeNO also related to higher blood neutrophil counts.