Evidence for using telehealth in Cystic Fibrosis (CF) is growing rapidly. A study evaluating digital technologies in the management of CF adults showed an improvement in patients' quality of life. The behavior of CF patients and their adherence regarding these new approaches need further investigations. The aim was to assess patient's adherence of using the NuvoAir Home platform as part of a virtual model of care.

BACKGROUND:The combination of cystic fibrosis transmembrane conductance regulator (CFTR) modulators elexacaftor, tezacaftor and ivacaftor (ELX/TEZ/IVA) has been approved for treatment of cystic fibrosis (CF) patients (pwCF) homozygous and heterozygous for Phe508del. We aim to assess the long-term effects of ELX/TEZ/IVA therapy on clinical outcomes in severe pwCF. METHODS:Lung function, pulmonary exacerbation (PEx), sweat chloride concentration, body mass index (BMI) and the respiratory domain of the cystic fibrosis questionnaire-revised (CFQ-R RD) were prospectively evaluated in a cohort of pwCF who were candidates for inclusion in a compassionate program of ELX/TEZ/IVA therapy. All procedures were performed at baseline and then at 12 and 24 months after initiation of modulator therapy. The number of PExs in the year before the study enrollment was collected from our records. RESULTS:Thirty-six adult pwCF (median age 36.7 years; BMI 19.8 kg/m2; FEV1 36.5% predicted) were recruited from 2019. At 12 and 24 months after initiation, the absolute change in ppFEV1 (percent predicted forced expiratory volume in 1 s) from baseline was +12.5% (p < 0.0001) and +13% (p < 0.0001), respectively. A median of 4.0 exacerbations per patient was reported in the preceding year, while the median number of PExs was 0.0 and 1.0 after 12 and 24 months, respectively, of modulator therapy (both p < 0.0001). After 12 and 24 months of ELX/TEZ/IVA therapy, the CFQ-R RD score improved by 22.4 points (p < 0.0001) and 16.7 points (p < 0.0001), and sweat chloride levels decreased by 65.5 mmol/L (p < 0.0001) and 60 mmol/L (p < 0.0001), respectively. BMI significantly increased. CONCLUSIONS:Long-term ELX/TEZ/IVA combination therapy markedly impacts the clinical status of patients with severe CF, showing a sustained improvement in lung function and PEx rate.

Background The combination of cystic fibrosis transmembrane conductance regulator (CFTR) modulators elexacaftor, tezacaftor and ivacaftor (ELX/TEZ/IVA) has been approved for treatment of cystic fibrosis (CF) patients (pwCF) homozygous and heterozygous for Phe508del. We aim to assess the long-term effects of ELX/TEZ/IVA therapy on clinical outcomes in severe pwCF. Methods Lung function, pulmonary exacerbation (PEx), sweat chloride concentration, body mass index (BMI) and the respiratory domain of the cystic fibrosis questionnaire-revised (CFQ-R RD) were prospectively evaluated in a cohort of pwCF who were candidates for inclusion in a compassionate program of ELX/TEZ/IVA therapy. All procedures were performed at baseline and then at 12 and 24 months after initiation of modulator therapy. The number of PExs in the year before the study enrollment was collected from our records. Results Thirty-six adult pwCF (median age 36.7 years; BMI 19.8 kg/m2; FEV1 36.5% predicted) were recruited from 2019. At 12 and 24 months after initiation, the absolute change in ppFEV1 (percent predicted forced expiratory volume in 1 s) from baseline was +12.5% (p < 0.0001) and +13% (p < 0.0001), respectively. A median of 4.0 exacerbations per patient was reported in the preceding year, while the median number of PExs was 0.0 and 1.0 after 12 and 24 months, respectively, of modulator therapy (both p < 0.0001). After 12 and 24 months of ELX/TEZ/IVA therapy, the CFQ-R RD score improved by 22.4 points (p < 0.0001) and 16.7 points (p < 0.0001), and sweat chloride levels decreased by 65.5 mmol/L (p < 0.0001) and 60 mmol/L (p < 0.0001), respectively. BMI significantly increased. Conclusions Long-term ELX/TEZ/IVA combination therapy markedly impacts the clinical status of patients with severe CF, showing a sustained improvement in lung function and PEx rate.

Digital service, compliments usual services, encouraged self-management and self-awareness of the relationship between treatment and health status and quality of life in adults with Cystic Fibrosis (CF). As technology has ongoing financial implications and is a continuous investment as new patients arrive, further investigations of costs are required. The aim of this study was to assess the long-term economic impact of the application of e-health as part of a virtual model of care in CF. NuvoAir Home platform consists of a smartphone application, Bluetooth spirometer and a clinician portal. Patients were trained to use the platform and asked to do home spirometry monthly. Patients continued face-to-face visit alternate to two time virtually via video call. Number of visits, pulmonary exacerbations, hospital admission, antibiotics cost, travel time and cost, time saved off work were prospectively collected. Costs are compared with data presented in the year before the study enrollment. Two-sided Wilcoxon signed-rank test was applied to all comparisons of before and after values. A cohort of 43 CF patients were recruited (26 females; mean age 31.6 ± 6.8; 16 homozygous for delta F508; FEV1 48.4 ± 16.3% predicted). Sustained improvement in travel cost and travel time was seen through 12 months, p < 0.02 and p < 0.05. We found significant improvement in time saved off work p <0.002. The average of number of exacerbations per person was 0.84 1-year before vs 0.09 1-year after the use of digital technology, p <0.0001. Health costs per person were 8.037,00 euro 1-year before vs 6.404,55 1-year after, mean change – 1.632,45 euro, p = 0.05. The application of digital technologies in the management of adults with CF showed an improvement in days off work, travel and health costs. As technology has financial implications, our data of a digital intervention may serve for planning future funding provision.

Introduction: Digital service, compliments usual services, encouraged self-management and quality of life in adults with Cystic Fibrosis (CF). As technology has ongoing financial implications, further investigations of costs are required. Aims and objectives: To assess the long-term economic impact of the application of e-health as part of a virtual model of care. Methods: NuvoAir Home platform consists of a smartphone application, Bluetooth spirometer and a clinician portal.Patients were trained to use the platform and asked to do home spirometry monthly.Patients continued face-to-face visit alternate to two time virtually via video call.Number of visits, pulmonary exacerbations, hospital admission, antibiotics cost, travel time and cost, time saved off work were prospectively collected.Costs are compared with data presented in the year before the study enrollment. Two-sided Wilcoxon signed-rank test was applied to all comparisons of before and after values. Results: 43 CF patients were recruited (26 females;mean age 31.6±6.8;16 homozygous for delta F508;FEV1 48.4±16.3 % predicted).Sustained improvement in travel cost and travel time was seen through 12 months, p< 0.02 and p<0.05.We found significant improvement in time saved off work p <0.002.The average of number of exacerbations per person was 0.84 1-year before vs 0.09 1-year after the use of digital technology, p <0.0001.Health costs per person were 8.037,00 euro 1-year before vs 6.404,55 1-year after, mean change -1.632,45 euro, p=0.05. Conclusions: The application of digital technologies in the management of adults with CF showed an improvement in days off work, travel and health costs. Our data of digital intervention may serve for planning future funding provision.

Background: The aim of this study was to assess the long-term clinical impact of the application of e-health as part of a virtual model of care in patients with Cystic Fibrosis (CF). Methods: Digital care group (DCG) were deemed suitable for using the NuvoAir Home platform to monitor their disease at home as part of a virtual model of care project. The usual care group (UCG) remained on usual care. NuvoAir Home platform consists of a smartphone application, Bluetooth spirometer and a clinician portal. Data on pulmonary function, Cystic Fibrosis Questionnaire-Revised (CFQR) and pulmonary exacerbations were collected at baseline and after twelve months. A survey for the digital care group was emailed to evaluate their experience using the technology. Results: Between February 2020 and May 2020 a cohort of 43 CF patients were recruited for the DCG (26 females; mean age 31.6 +/- 6.8; 16 homozygous for delta F508; FEV1 48.4 +/- 16.3% predicted) and 36 CF patients for UCG (18 females; mean age 29.1 +/- 9.4; 6 homozygous for delta F508; FEV1 77.0 +/- 25.0% predicted). CFQ-R score improved significantly through 12 months in the DCG with a mean change of 13.8 points, p < 0.0001, and no changes for the UCG (p = 0.73). When we analyzed the subgroup of CF patients on digital and usual care who did not receive CFTR modulator therapy, we found a change in CFQ-R score which was significantly associated with the use of digital technology while adjusting for baseline differences (p = 0.020). There was no significant difference in the change in lung function and number of exacerbations. 90% of patients reported they understood their CF better using the NuvoAir Home platform. No changes in medical treatment were reported during that time. Conclusions: The application of digital technologies in the management of adults with CF showed an improvement in patients' quality of life. Using a virtual model of care was well accepted by CF patients and improved their understanding of their medical condition.

Figure 1.Values before and 4 to 8 weeks after starting treatment with elexacaftor/ tezacaftor/ivacaftorConclusions: These seven patients with N1303K and a second nonresponsive mutation demonstrated significant clinical improvement after treatment with ELX/TEZ/IVA.A controlled clinical trial is needed to confirm these results and allow people with the N1303K mutation to register and be reimbursed.

Background: Over the last decades aggressive interventions have been successful to improve nutritional outcomes in people with cystic fibrosis (CF). As a result, with improvement of life expectancy and new CFTR modulators, overweight and obesity are progressively becoming a source of concern for adult population and in developed countries. Methods: This was a multicenter, observational, cross-sectional study of 321 adults with CF at three large CF centers in Italy. Patients were divided into three groups according to BMI classes, overweight and obesity (OW) group including patients with BMI >= 25 kg/m(2), normal weight (NW) group with BMI 18.6-24.9 kg/m(2) and underweight (UW) group with BMI <= 18.5 kg/m(2). Results: We demonstrated that prevalence of OW in adults with CF in Italy is 22%. OW status is independently associated with male sex (OR 3.520, P = 0.001), pancreatic sufficiency (OR 2.873, P = 0.014) and older age at diagnosis (1.015, P = 0.042). BMI correlated with ppFEV1 (r = 0.337; P<0.0001) with median ppFEV1 significantly higher in patients with OW than comparisons. We also reported preliminary data on unfavorable cardiovascular risk factors in a subgroup of patients, where median blood levels [IQR] of cholesterol and systemic hypertension [%] were significantly higher in the OW group than in the NW and UVV. Conclusions: People with CF and OW is a relevant patient group that might deserve better definition and proper clinical management. (C) 2021 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Introduction: Cystic Fibrosis (CF) centers globally increased the number of telehealth clinics during the Covid-19 pandemic and developed processes utilizing telemedicine to replace a standard clinic visit. Whether these new approaches provide an opportunity to improve patients’ clinical condition need further investigations. Aims and objectives: To assess the short-term clinical impact of using the NuvoAir Home platform to monitor children and adolescents with CF at home for six months as part of a virtual model of care. Methods: The NuvoAir Home platform consists of a smartphone application, Bluetooth spirometer and clinician portal. Patients and/or parents were trained to use the platform and asked to do home spirometry monthly. Cystic Fibrosis Questionnaire-Revised (CFQ-R) was collected at the time of study entry and after six months. We calculated the percentage of change between "pre" and "post" conditions of the variables. Results: Sixteen children and adolescent CF patients from Federico II Hospital, Naples, Italy (9 females; mean age 16.3±0.9; 5 homozygous for delta F508; FEV1 79.5±26.2 % predicted; FVC 91.6±23.6 % predicted; BMI 21.5±3.8) were recruited from June 2021. All patients had completed six months follow-up. CFQ-R revealed higher scores indicating a higher patient-reported quality of life with regard to “health perception” + 3%, “social limitations” + 11%, “digestive symptoms” + 6%. We observed a 2 % improvement from baseline in FEV1 % predicted. There was no difference in pulmonary exacerbation versus the previous year. No changes of medical treatment were reported during that time. Conclusions: Digital technology for home monitoring in children and adolescents with cystic fibrosis led to improved quality of life and lung function.

Rationale: A common symptom of worsening respiratory disease is an increase in cough. Patients currently self-report changes in cough as part of routine follow-up. However, self-reports are inaccurate. This project evaluated an automated process for quantifying cough during sleep. Methods: A proprietary deep learning model was developed to detect “cough-events” from audio collected with a smartphone. The model was trained using data from 169 subjects from publicly available sources and the University of Ioannina, Greece. Data consisted of coughs from healthy controls and patients with asthma and COPD. The trained model was evaluated in a quiet ‘nighttime like’ environment at the University of Ioannina, Greece with a new cohort of 40 subjects (15 male, age 54.6±12.2, 21 healthy controls, 5 asthmatics, 11 COPD and 3 other respiratory diseases). A total of 5 coughs were recorded from each subject at intervals of 30 seconds. Recordings were annotated by a respiratory physician and analyzed offline using the trained model. Results: In total 218 events were counted by the physician and 221 detected by the model. The model showed good agreement with the physician annotations, with a true positive rate (precision) of 84% and recall rate of 85%. On average, there was a 1.1±1.45 difference between physician counted events and the model. Comparing healthy and unhealthy subjects there was an average difference between annotator and system of 1.28±1.7 for healthy patients, and 0.95±1.2 for unhealthy patients Conclusion: The model shows good agreement with annotations from a respiratory physician. The recall and precision of the model was sufficiently high to give an accurate measurement of a patient’s nocturnal cough trend.

Objectives: The effect of the COVID-19 pandemic on the quality of life (QOL) of people with cystic fibrosis ( pwcf ) remains unclear.This study investigated the change in QOL, measured by the CFQ-R, in adult pwcf prior to and during the COVID-19 pandemic.Methods: The CFQ-R scores of 88 adult pwcf completed at two routine clinic appointments (one prior to first COVID-19 case in Wales 28/2/20 and one post) were retrospectively reviewed.Any change in CFTR modulator therapy between these dates was recorded along with demographics, FEV 1 % and BMI.Results: 88 (52 male, 36 female) with mean age, FEV 1 % and BMI of 32.2 years, 61.6% and 22.7 kg/m 2 respectively had two consecutive CFQ-R results in the above time frame.Overall, mean social domain scores significantly declined (60.4 to 54.2 p < 0.001) and mean emotion scores fell from 69.3 to 65.9 ( p = 0.07).Results did not vary between males and females.59/88 had a change in modulator status during this period, mainly commencing Symkevi ® or triple modulator therapy, and this group experienced a significant increase in FEV 1 % ( p < 0.01) and BMI ( p = 0.02) and a statistically significant improvement in every domain of the CFQ-R except emotion, eating, digestion and social.Their mean social score dropped significantly 59.5 to 54.2 ( p = 0.018).Of the 29 pwcf with no change in modulator status, there was no significant change in FEV 1 % or BMI.Mean emotion domain scores, which assesses feelings of being sad, useless, lonely and difficulty making future plans, significantly worsened from 78.1 to 70.6 ( p = 0.018).Mean social scores decreased from 62.1 to 54.2 ( p = 0.037).Conclusion: This is the first study looking at QOL during COVID-19 in pwcf.During the COVID-19 pandemic there have been developments in access to highly effective modulators, but despite improvements in FEV 1 %, BMI and many CFQ-R domains suggesting improved health, emotion and social domain scores fell.This is likely to reflect the effect of the COVID-19 pandemic.

In the physiopathology of cystic fibrosis (CF), oxidative stress implications are recognized and widely accepted. The cystic fibrosis transmembrane conductance regulator (CFTR) defects disrupt the intracellular redox balance causing CF pathological hallmarks. Therefore, oxidative stress together with aberrant expression levels of detoxification genes and microRNAs (miRNAs/miRs) may be associated with clinical outcome. Using total RNA extracted from epithelial nasal cells, the present study analyzed the expression levels of oxidative stress genes and one miRNA using quantitative PCR in a representative number of patients with CF compared with in healthy individuals. The present pilot study revealed the existence of an association among CFTR, genes involved in the oxidative stress response and miR-125b. The observed downregulation of CFTR gene expression was accompanied by increased expression levels of Nuclear factor erythroid derived-2 like2 and its targets NAD(P)H:Quinone Oxidoreductase and glutathione S-transferase 1. Moreover, the expression levels of heme oxygenase-1 (HO-1) and miR-125b were positively correlated with a forced expiratory volume in 1 sec (FEV1) >60% in patients with CF with chronic Pseudomonas aeruginosa lung infection (r=0.74; P<0.001 and r=0.57; P<0.001, respectively). The present study revealed the activation of an inducible, but not fully functional, oxidative stress response to protect airway cells against reactive oxygen species-dependent injury in CF disease. Additionally, the correlations of HO-1 and miR-125b expression with an improved FEV1 value suggested that these factors may synergistically protect the airway cells from oxidative stress damage, inflammation and apoptosis. Furthermore, HO-1 and miR-125b may be used as prognostic markers explaining the wide CF phenotypic variability as an additional control level over the CFTR gene mutations.

Hintergrund: Die Lockdown-Phasen während der anhaltenden Coronavirus-Pandemie mit der Erkrankung COVID-19 haben die Art und Weise verändert, wie Personen und Gemeinschaften leben, arbeiten und interagieren. Fallvorstellung: Der vorliegende Fallbericht beschreibt eine ungewöhnliche, aber bedeutende Manifestationsform der allergischen bronchopulmonalen Aspergillose (ABPA) bei einem zuvor gesunden Mann, der zu Beginn des landesweiten Lockdowns in Italien während der COVID-19-Pandemie beschloss, in den Keller seines Hauses zu ziehen. Da eine hochauflösende Computertomographie (HRCT) des Thorax bei Aufnahme des Patienten diffuse miliäre Noduli zeigte, bestand initial der Verdacht auf eine Miliartuberkulose. Weitergehende Untersuchungen führten allerdings zur Diagnose einer ungewöhnlichen Manifestationsform der ABPA. Schlussfolgerungen: Der vorliegende Fall unterstreicht die Bedeutung einer ungebrochenen Aufmerksamkeit in Bezug auf Aspergillus-assoziierte Erkrankungen des Respirationstrakts während der COVID-19-Pandemie, insbesondere aufgrund dessen, dass Änderungen der Lebensführung im Zusammenhang mit häuslicher Isolation mit dem erhöhten Risiko für eine Exposition gegenüber Schimmelpilzsporen in einigen Wohnräumen verbunden sind.

Objectives: The aim of this study was to assess the long-term clinical impact of using the NuvoAir Home platform to monitor patients with cystic fibrosis (CF) for more than six months as part of a virtual model of care. Methods: The NuvoAir Home platform consists of a smartphone application, Bluetooth spirometer and a clinician portal. Patients were trained to use the platform and asked to do home spirometry monthly. After each consultation, a survey was emailed to patients to evaluate their experience with the technology. Results: Forty-five consecutive adult CF patients from Federico II Hospital, Naples, Italy (18 males; mean age 31.6±6.7; 17 homozygous for delta F508; FEV1 48.1±16.5 % predicted; FVC 62.9±18.2 % predicted; BMI 22.8±2.8) were recruited from May 2020. A total of 22 (49 %) had completed six months follow-up. Survey responses from all patients showed that the NuvoAir Home platform was easy to use and was a good tool to monitor lung function at home. The vast majority of patients (91,0%) reported that using the NuvoAir Home platform to share results with their CF team improved consultations and that they understood their CF better (81,8%). After six months of using the NuvoAir Home platform, we observed a 5.4% improvement from baseline in FEV1 % predicted, 14.3% in FVC % predicted and 66% reduction in pulmonary exacerbation vs. the previous year. No changes of medical treatment were reported during that time. Conclusions: The NuvoAir Home platform was well accepted by patients with CF and improved their understanding of their medical condition. Using the NuvoAir Home platform led to improved lung function and a reduction in pulmonary exacerbations.

BACKGROUND:During the ongoing pandemic of coronavirus disease 2019 (COVID-19), lockdown periods have changed the way that people and communities live, work and interact.CASE PRESENTATION:This case report describes an uncommon but important presentation of allergic bronchopulmonary aspergillosis (ABPA) in a previously healthy male, who decided to live in the basement of his house when Italy entered a nationwide lockdown during the COVID-19 pandemic. As high resolution computed tomography (HRCT) of the chest on admission showed diffuse miliary nodules, a miliary tuberculosis was initially suspected. However, further investigations provided a diagnosis of unusual presentation of ABPA.CONCLUSIONS:This case highlights the importance of maintaining awareness of Aspergillus-associated respiratory disorders during the COVID-19 pandemic, especially because lifestyle changes associated with home isolation carry an increased risk of exposure to mold spores present in some indoor environments.

Overweight and obesity are progressively becoming a source of concern in cystic fibrosis (CF) care, especially in adult population and in developed countries. The main objectives of this study is to investigate the epidemiological impact of overweight in a large multicentric population of adults with CF. We performed a cross-sectional analysis of the Milano-Roma database enrolling adult CF patients and followed up from 2006 to 2016 at three major CF centers in Italy. Three groups were selected according to BMI classes: overweight group (OW) including BMI >=25 kg/m2, normal weight group (NW) including BMI 18.1 - 24.9 kg/m2 and underweight group (UW) including BMI <=18 kg/m2. A total of 321 patients were included. Median BMI in our cohort was 22.3 kg/m2 (20.9-24.4) with 4% UW. Patients with OW were 71 (22%). OW group were likely to be male (OR 3.212, p <0.0001), older at diagnosis (OR 0.995, p 0.003), pancreatic sufficiency (OR 2.656, p <0.0001), lower prevalence of P. aeruginosa infection (OR 1.250, p 0.032) and less pulmonary exacerbations in the previous year (OR 1.011, p 0.014). Genotypes with at least one residual function mutation were more prevalent in OW than in UW (21.1% vs 0%, p 0.023). FEV1 was significantly higher in OW group than NW and UW (91.0 vs 70.0 vs 49.0, P< 0.0001) and showed a positive correlation with BMI (R 0.337, P< 0.0001). OW group showed total cholesterol levels significantly higher than other groups (p 0.006). OW status was common in a large cohort of patients from Italy. Respiratory parameters were better in the OW group compared to the others, while blood lipid levels were higher in OW.