Telemedicine and home spirometry in cystic fibrosis: A prospective multicenter study.

OBJECTIVES: Telehealth and home spirometry feasibility for children has been established, but their impact on cystic fibrosis (CF) disease progression remains unassessed. We aimed to evaluate the effects of telehealth and home spirometry on CF disease progression and care. METHODS: Children with CF aged 5-17 years from all Swedish CF centers were provided with home spirometers. A minimum of two in-person visits were replaced with telemedicine visits and participants were instructed to conduct home spirometry before visits. Linear mixed-effects models were used to compare annual CF disease trajectories during the intervention period and prepandemic period (1 January 2019 to 28 February 2020). Participants and caregivers completed study questionnaires. RESULTS: A total of 59 individuals completed the study over a mean (SD) period of 6.8 (1.4) months, made 3.1 (1.0) physical visits and 2.2 (0.6) telehealth visits per patient year during the study period. The mean difference (95% CI) between the intervention and prepandemic period progression rate for FEV1%, lung clearance index and BMI were -0.4 (-1.3 to 0.5, p = 0.39), 0.11 (-0.07 to 0.28, p = 0.25) and -0.02 (-0.13 to 0.08, p = 0.70), respectively. There were no major shifts in the incidence of airway pathogens, sputum cultures, or antibiotics use between the periods (p > 0.05). The intervention did not increase stress. Almost all participants and caregivers expressed a desire to continue with home spirometry and telemedicine. CONCLUSION: Combining telehealth and physical visits with access to home spirometry demonstrated comparable effectiveness as exclusively in-person care with enhanced flexibility and personalization of CF care.

Clinical, economic, and societal burden of cystic fibrosis and the impact of the CFTR modulator, lumacaftor/ivacaftor: an assessment using linked registry data in Sweden.

AIMS: We aimed to describe the clinical, economic, and societal burdens of cystic fibrosis (CF) and impact of CF transmembrane conductance regulator modulator (CFTRm) treatment on people with CF, caregivers, and healthcare systems. MATERIAL AND METHODS: This retrospective study used linked real-world data from Swedish national population-based registries and the Swedish CF Quality Registry to assess clinical, economic, and societal burden and CFTR impact in CF. Records from people with CF and a ten-fold control population without CF matched by sex, birth year, and location were compared during 2019. Outcomes for a subset aged >6 years initiating lumacaftor/ivacaftor (LUM/IVA) in 2018 were compared 12 months pre- and post-treatment initiation. RESULTS: People with CF (n = 743) had >10 times more inpatient and outpatient specialist visits annually vs controls (n = 7406). Those aged >18 had an additional 77·7 (95% CI: 70·3, 85·1) days of work absence, at a societal cost of €11,563 (95% CI: 10,463, 12,662), while caregivers of those aged <18 missed an additional 6.1 (5.0, 7.2) workdays. With LUM/IVA treatment, people with CF (n = 100) had significantly increased lung function (mean change in ppFEV1 [3·8 points; 95% CI: 1·1, 6·6]), on average 0·5 (95% CI: -0·8, -0·2) fewer pulmonary exacerbations and 45·2 (95% CI: 13·3, 77·2) fewer days of antibiotics. Days of work lost by caregivers of people with CF aged <18 decreased by 5·4 days (95% CI: 2·9, 7·9). CONCLUSION: CF is associated with a high clinical economic and societal burden in Sweden. Improvements in clinical status observed in people with CF treated with LUM/IVA were reflected in reduced caregiver and societal burden.

Cystic fibrosis (CF) is a disease caused by a single faulty gene called CFTR, which affects the lungs, pancreas, and other organs. Medications known as CFTR modulators help improve the function of this faulty gene and have shown benefits for people with CF. In Sweden, two such medicines, lumacaftor and ivacaftor (LUM/IVA), have been available since July 2018 for treating CF. This study looks at the impact of CF on patients, caregivers, and the healthcare system, as well as the benefits of CFTR modulators. Using data from Swedish national healthcare and social insurance registries, the study compared 743 people with CF in 2019 to about 7400 people without CF, matched by sex, birth year, and location. The findings show that people with CF had 24 times higher direct healthcare costs, including outpatient visits, hospitalizations, and CF-related medications, totaling 23,233 Euros. Indirect costs, such as work absences for those over 18 with CF anssd caregivers' absences to care for sick children, were 9,629 Euros, which is five times higher than the general population. Those over 6 years old treated with LUM/IVA showed improved lung health, reduced hospitalizations (though not significantly), and needed fewer antibiotics. Caregivers' work absences decreased, but there was no change in work absences for adults with CF. Overall, treatment with LUM/IVA improved clinical outcomes and reduced the burden on caregivers and society.

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.

Nasal nitric oxide in relation to asthma characteristics in a longitudinal asthma cohort study.

OBJECTIVE: Cross-sectional studies report relations between low nasal nitric oxide (nNO) and poor asthma control and between low nNO and chronic rhinosinusitis (CRS). In our cohort study, we studied if changes in nNO related to changes in asthma control, symptoms of CRS, or asthma or rhinitis medication. METHODS: A total of 196 subjects with predominantly mild to moderate asthma, aged 10-35 years, performed nNO measurements at both baseline and follow-up after a median of 43 (range 23-65) months. Asthma control, CRS symptoms, and medication, were questionnaire-assessed at both timepoints. IgE sensitisation against aeroallergens was quantified at baseline. RESULTS: There was an increase in nNO between baseline and follow-up (764 ± 269 ppb vs. 855 ± 288 ppb, p < 0.001). When adjusted for covariates, a larger increase in nNO was found in subjects sensitised to perennial aeroallergens than those not sensitised (92 (16-167) ppb), as well as in subjects with daily use of inhaled corticosteroids (ICS) at baseline but not at follow-up than those on ICS daily at both timepoints (146 (51-242) ppb). In the same model, subjects using nasal steroids daily at both timepoints had decreased nNO compared with those without such treatment at both timepoints (-185 (-321-(-48)) ppb). No relations between changes in nNO levels and changes in asthma control or symptoms of CRS were found. CONCLUSION: Longitudinal changes in nNO were not related to changes in asthma control, but were related to changes in asthma or rhinitis medication.

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.