Background: To limit the progression of disease, people with cystic fibrosis (pwCF) perform daily respiratory physiotherapy, which is perceived as the most burdensome routine in managing their condition. The elexacaftor–tezacaftor–ivacaftor (ETI) combination has changed respiratory management. Objective: To investigate how the perceived treatment burden changed in 1 year of treatment with ETI. Design: Prospective observational study. Methods: Ad hoc questionnaires for the pwCF and for the caregivers of pwCF < 18 years were administered before the initiation of ETI therapy and then at 6–12 months. The Cystic Fibrosis Questionnaire-Revised (CFQ-R) and the Sinonasal Outcome Test (SNOT-22) were administered to explore disease-related symptoms and social limitations. The International Physical Activity Questionnaire was used to determine levels of physical activity. Mixed-effect models were fitted to explore whether the time engaged in respiratory physiotherapy changed during 1 year. Results: The study included 47/184 pwCF aged 21.4 (5.7) years, who completed 1 year of ETI therapy. At 6 months, time on aerosol therapy was decreased by 2.5 (95% CI −32.9 to 27.8) min/day, time on airway clearance therapies (ACTs) was decreased by 8.8 (95% CI −25.9 to 8.3) min/day, and time for cleaning and disinfecting respiratory equipment was decreased by 10.6 (95% CI −26.5 to 5.3) min/day. At 1 year, gains in time saved were nearly 15 min/day on average. At 1 year, 5/47 (10.6%) pwCF reported that they had discontinued positive expiratory pressure mask. Conclusion: PwCF on ETI may note less time engaged in their daily respiratory physiotherapy routine. Nonetheless, aerosol therapy, ACTs and maintaining respiratory equipment were still perceived as time-consuming daily activities.

Background: Can physiotherapy with a positive expiratory pressure (PEP) mask improve peripheral ventilation inhomogeneity, a typical feature of children with cystic fibrosis (cwCF)? To answer this question, we used the nitrogen multiple-breath washout (N2MBW) test to measure diffusion-convection-dependent inhomogeneity arising within the intracinar compartment (S-acin*VT). Methods: For this randomized, sham-controlled crossover trial, two N2MBW tests were performed near the hospital discharge date: one before and the other after PEP mask therapy (1 min of breathing through a flow-dependent PEP device attached to a face mask, followed by three huffs and one cough repeated 10 times) by either a standard (10-15 cmH(2)0) or a sham (<5 cmH(2)0) procedure on two consecutive mornings. Deception entailed misinforming the subjects about the nature of the study; also the N2MBW operators were blinded to treatment allocation. Study outcomes were assessed with mixed-effect models. Results: The study sample was 19 cwCF (ten girls), aged 11.4 (2.7) years. The adjusted S-acin*VT mean difference between the standard and the sham procedure was -0.015 (90% confidence interval [CI]: -infinity to 0.025) L-1. There was no statistically significant difference in S-cond*VT and lung clearance index between the two procedures: -0.005 (95% CI: -0.019 to 0.01) L-1 and 0.49 (95% CI: -0.05 to 1.03) turnovers, respectively. Conclusion: Our findings do not support evidence for an immediate effect of PEP mask physiotherapy on S-acin*VT with pressure range 10-15 cmH(2)0. Measurement with the N2MBW and the crossover design were found to be time-consuming and unsuitable for a short-term study of airway clearance techniques.

BackgroundAn exercise test combined with a multiple breath washout nitrogen test (MBWN2) may offer a comprehensive clinical evaluation of cystic fibrosis (CF) disease in children with normal spirometry. The purpose of the present study is to explore whether information derived from spirometry, MBWN2, and exercise tests can help the CF multidisciplinary team to characterize time free from hospitalization due to pulmonary exacerbation (PE) in a cohort of pediatric patients with CF.MethodsThis prospective observational study was carried out at the Lombardia Region Reference Center for Cystic Fibrosis in Milano, Italy. In 2015, we consecutively enrolled children and adolescents aged <18 years with spirometry, MBWN2, and Godfrey exercise test performed during an outpatient visit.ResultsOver a median follow-up time of 2.2 years (interquartile range [IQR], 2.01; 3.18), 28 patients aged between 13.0 and 17.4 years were included. When lung functions were outside the normal range, 50% of patients were hospitalized 4 months after the outpatient visit, and their response to exercise was abnormal (100%). Half of the individuals with normal forced expiratory volume in the first second (FEV1) and abnormal lung clearance index (LCI) experienced the first hospital admission 9 months after the clinic visit, and 84.2% presented an abnormal response to exercise. Conversely, 15.8% had abnormal exercise responses when lung functions were considered normal, with half of the adolescents hospitalized at 11 months.ConclusionMaintaining ventilation homogeneity, along with a normal ability to sustain intense work, may have a positive impact on the burden of CF disease, here conceived as time free from hospitalization due to PE.

Abstract Background Lung clearance index (LCI) is accepted as an early marker of lung disease in cystic fibrosis (CF), however the utility of LCI to identify subgroups of CF disease in the paediatric age group has never been explored. The aim of the study was to characterize phenotypes of children with CF using LCI as a marker of ventilation inhomogeneity and to investigate whether these phenotypes distinguished patients based on time to pulmonary exacerbation (PE). Methods Data were collected on patients with CF aged < 18 years old, attending the CF Center of Milan during outpatient follow-up visits between October 2014 and September 2019. Cluster analysis using agglomerative nesting hierarchical method was performed to generate distinct phenotypes. Time-to-recurrent event analysis investigated association of phenotypes with PE. Results We collected 313 multiple breath washout tests on 125 children aged 5.5–16.8 years. Cluster analysis identified two divergent phenotypes in children and adolescents of same age, presenting with almost normal FEV1 but with substantial difference in markers of ventilation inhomogeneity (mean LCI difference of 3.4, 95% Confidence Interval [CI] 2.6–4.2). A less severe phenotype was associated with a lower risk of PE relapse (Hazard Ratio 0.45, 95% CI 0.34–0.62). Conclusions LCI is useful in clinical practice to characterize distinct phenotypes of children and adolescents with mild/normal FEV1. A less severe phenotype translates into a lower risk of PE relapse.

Background Individuals with cystic fibrosis (CF) are deemed to have a higher risk of developing urinary incontinence (UI), likely due to repeated increasing pressure on the pelvic floor. We aimed to determine the prevalence of female UI in a large CF referral center, and to assess the association between UI and severity of CF disease. Methods We consecutively recruited female patients regularly attending our CF center, aged >= 6 years and with a confirmed diagnosis of CF. Prevalence, severity, and impact of UI were assessed by administering two validated questionnaires. Relationship between variables was evaluated by means of multiple correspondence analysis, whereas a logistic model was fitted to capture the statistical association between UI and independent variables. Results UI was present in 51/153 (33%, 95% confidence interval [CI]: 26%-41%) females. Among children and adolescents, the prevalence was 12/82 (15%, 95% CI: 8%-25%) whereas among adults was 39/71 (55%, 95% CI: 43%-67%). The only explanatory variable associated with UI was age, with children presenting the lowest risk (odds ratio, 0.32; 95% CI: 0.05-0.93). Females presenting low or high nutritional status show higher profile risk of having UI. Conclusions Stress UI is a common complication in females with CF since childhood. Although it frequently occurs in older patients with a more severe phenotype, much attention should be paid to adults and to their nutritional status.

PURPOSE:The 2010 Lung Allocation Score (LAS) version considers the estimated survival benefit offered by lung transplantation (LTx) and uses 6-minute Walk Test (6MWT) distance as a dichotomous covariate of whether an individual can walk more than 150 ft or 45.7 m in 6 min. This study aimed to provide evidence that 6MWT gives no clinically meaningful information to be used in the current LAS for candidates to LTx with cystic fibrosis (CF). MATERIALS AND METHODS:We collected data from 6MWTs performed since 2003 at our CF centre. A joint model was fitted to describe the effect of changes in walked distance on the hazard of LTx or death. RESULTS:Up to 2019, 552 6MWTs were performed on 163 individuals with CF. None of the individuals included walked for less than 45.7 m during the 6MWT. Based on the joint modelling, the association of walked distance with the hazard ratio (HR) of LTx or death was significant (HR 0.99, 95% Credible Interval [CI]: 0.99 to 1.00). CONCLUSIONS:When adopted dichotomously for LAS calculation, walked distance does not add any useful information about exercise capacity. Longitudinal trajectories of walked distance may provide complementary information about prognosis in individuals with CF.Implications for rehabilitationDichotomized walked distance does not contribute to lung allocation score in candidates to lung transplantation with cystic fibrosisChanges in the longitudinal trajectory of walked distance can be clinically meaningful for prognostication.Sensitive outcomes to be incorporated in the lung allocation scoring system for individuals with CF are yet needed to catch rapid falls in functional capacity.

Background During Coronavirus Disease 2019 (COVID-19) outbreak in Lombardia, people were recommended to avoid visiting emergency departments and attending routine clinic visits. In this context, it was necessary to understand the psychological reactions of patients with chronic diseases. We evaluated the psychological effects on patients with chronic respiratory conditions and inflammatory bowel disease (IBD) through the analysis of their spontaneous contacts with their referral centres. Methods Cross-sectional study was conducted from February 23 to April 27, 2020 in patients, or their parents, who contacted their multidisciplinary teams (MDT). E-mails and phone calls directed to the MDT of the centre for cystic fibrosis (CF) in Milano and for paediatric IBD in Bergamo, were categorised according to their contents as information on routine disease management, updates on the patient's health status, COVID-19 news monitoring, empathy towards health professionals, positive feedback and concern of contagion during the emergency. Results One thousand eight hundred and sixteen contacts were collected during the study period. In Milano, where the majority of patients were affected by CF, 88.7% contacted health professionals by e-mail, with paediatricians receiving the largest volume of emails and phone calls compared with other professionals (P< .001). Compared with Milano, the centre for IBD in Bergamo recorded more expression of empathy towards health professionals and thanks for their activity in the COVID-19 emergency (52.4% vs 12.7%, P< .001), as well as positive feedback (64.3% vs 2.7%, P = .003). Conclusion One of the most important lessons we can learn from COVID-19 is that it is not the trauma itself that can cause psychological consequences but rather the level of balance, or imbalance, between fragility and resources. To feel safe, people need to be able to count on the help of those who represent a bulwark against the threat. This is the role played, even remotely, by health professionals.

Inhaled therapies are relatively simple and easy to be managed however ineffective use of aerosols when self-administered may occur. We described variation of the number of clinic visits, lung function and number of antibiotic courses performed over 12 months in participants with cystic fibrosis (CF), when supervised or not by physiotherapists (PTs) at home. Participants in 8 Italian CF centers with a prescription of dry-powder antibiotic choose whether to be supervised at home (PT-FU) or not (non-PT-FU), in adjunct to routine clinic visits. PTs assisted participants with their inhaled therapies regimen and reviewed the airway clearance program in use. Mixed-effect regression models were fitted to evaluate the variation of selected endpoints over time. A total of 163 participants were included. Lung function declined over time in both groups, at higher extent in the non-PT-FU group at 6 months (-1.8, 95%CI: -4.4 to 0.7 % predicted), without reaching statistical significance, whereas in the PT-FU group only, nearly one visit less was recorded (p = 0.027). Regardless the type of supervision adopted, the number of antibiotic courses did not change compared to the previous year. We counted 19/90 (21.1%) drop-out in the PT-FU, double compared to the group followed up at the clinics (p=0.065). Participants under a course of an inhaled antibiotic therapy showed a 1-year decline in lung function, whereas only the group receiving home supervision counted nearly one visit less at the CF center, whose clinical relevance should be further discussed.

shows there is a need for standardisation when predicting MVV.

BACKGROUND:Lung clearance index (LCI2.5 ) is a marker of overall lung ventilation inhomogeneity and has proven to be able to detect early peripheral damage in subjects with cystic fibrosis (CF), with greater sensitivity than conventional spirometry. Combining its sensitivity with the output of an incremental exercise testing, we hypothesized that any sign of ventilation inhomogeneity in subjects without severe airflow obstruction and with a normal exercise tolerance could be relevant for the CF team, tracking early lung disease and potential exercise limiting factors. METHODS:Patients with CF in clinical stable conditions were recruited between 2015 and 2017. Available spirometry, nitrogen multiple-breath washout test and symptoms-limited exercise testing performed as parts of patients' annual routine evaluation were considered for this cross-sectional study. To describe the relationship between exercise intensity and ventilation inhomogeneity, a linear regression analysis was performed using backward elimination based on Akaike information criteria. RESULTS:Seventy-seven patients (38 females) were included. Sacin and LCI2.5 were significantly higher in patients with an overall reduced exercise tolerance. Peak work developed during exercise was associated with body mass index (b = 5.25; 95% confidence interval [CI] = 1.53-8.98), forced expiratory volume in 1 second (FEV1 ; b = 3.71; 95% CI = 1.96-5.46), Pseudomonas aeruginosa chronic infection (b = -8.84; 95% CI = -15.84 to -1.84) but not with LCI2.5 . CONCLUSION:Exercise capacity and airflow obstruction are associated in this Italian CF cohort. Considering the greater discriminatory power of LCI2.5 over FEV1 and peak work, the Godfrey protocol without gas analysis cannot provide detailed information about lung function or efficiency. However, this incremental protocol without gas exchange measures can still provide the CF team with information about exercise tolerance and disability.

Background: Time spent by patients in daily management of cystic fibrosis (CF) affects adherence, therefore the choice of aerosol delivery device system becomes important, in order to achieve good lung deposition and satisfactory compliance. The I-Neb Adaptive Aerosol Delivery (AAD) system results in shorter treatment times and better deposition of the drug, if used properly. Most importantly, this device allows patients, caregivers and CF team to have feedback on the ongoing therapy. The aim of this study was to evaluate the change in recorded adherence and inhalation technique of patients with CF using I-Neb after an educational intervention (EI). Methods: This descriptive study was run at the CF Paediatric Centre of Milan. All patients using I-Neb and registered to online software “Insight Online” (IoL) were evaluated by respiratory physiotherapists during regular outpatient visits. EI consisted of 2 sessions: some theory to explain the technical characteristics of the device and cleaning and disinfection procedures, and some practice using a training software with visual feedback to optimize inhalation. Baseline and one-month follow-up data about adherence, inhalation, nebulization time before and after EI was analysed. Privacy rule authorization was obtained according to the local Ethics Committee. Results: 24 patients (14 females) with CF, aged 5 to 34 y old, with a mean (SD) kg/m2 of 78(22)%pred. were included: 22 used Target Inhalation Mode (TIM) and 2 Tidal Breathing Mode (TBM). I-Neb compliance before EI was 74.5(33.7)%. Using TIM, mean nebulization time was 2.8(2.2) min; mean time with TBM was higher: 5.5(1.2) min. The mean inhalation time per breath using TIM was 2.8(2.5) s while using TBM was 1.4(1.1) s. The mesh performance was 84.6(38.5)%. After EI, the I-Neb use increased by 11.8%, the mesh performance grew of 6.4%. The rest time decreased by 2.9%. The inhalation time per breath using TIM increased of 1.2 s, using TBM 0.7 s. Nebulization time decreased for patients using TIM (0.4 min) while increased of 2.7 min using TBM. Conclusions: There was space for little improvements in the inhalation technique and device maintenance in the observed sample, even considering the optimal starting level. TIM offers several advantages over TBM, increasing the likelihood of a more effective inhaled therapy with shorter administration time. EI should be always part of the routine evaluation of patients with CF.

acceptability; rates of recruitment, retention and completion of measures (adherence [DPD], parental depression/anxiety [HADs], and care challenges [CLCF-SF]); change in outcome scores.Assessed at baseline and after 4 and 8 weeks.Qualitative interviews explored parents' experiences/ acceptability of the intervention.Inclusion criteria: child with CF aged 1 month to ≤8 years old whose parent/carer administers home physiotherapy.Results: Community recruitment failed.71% of 14 invited NHS clinics took part (N = 10).75% of 292 screened patients were eligible (N = 219).NHS recruitment rate (11%), participant recruitment (100%) and retention (85%), measure completion (100%), intervention acceptability (100%) and scores on measures exceeded targets of 10%, >50%, ≥70%, ≥80%, ≥75% and "stay the same/improve" respectively.23 parents returned completed consent forms; 20 were contacted, recruited and took part.Attrition was 15% (N = 3).17 parents (100%) used the film which they saw as acceptable (supportive, non-patronising).Only 7 used the action plan due to lack of perceived need related to high baseline adherence (N = 14/20 adherent).Overall, 8 weeks after baseline, the trend for adherence increased (mean difference in N physiotherapy sessions = 0.68 (5.07)).Reported parental anxiety (mean difference = -2.53(2.38), depression (mean difference = -0.71(1.92)) and perceived care challenges decreased (mean difference = -2.33 (6.26)).

Purpose: The aim of this study was to determine the level of consensus among Italian health care professionals (HCPs) regarding factors that influence adherence to cystic fibrosis (CF) treatments. Methods: A Delphi questionnaire with 94 statements of potential factors influencing adherence was developed based on a literature review and in consultation with a board of experts (n = 4). This was distributed to a multidisciplinary expert panel of HCPs (n=110) from Italian CF centers. A Likert scale was used to indicate the level of agreement (1= no agreement to 9= maximum agreement) with each statement. Three rounds were distributed to establish a consensus (>= 80% of participant ratings within one 3-point region) and, at the third round, assign a ranking to each statement with a high level of agreement (consensus in the 7-9 range) only. Results: Of 110 HCPs (from 31 Italian CF centers who were surveyed), responses were obtained from 85 (77%) in the first, 78 (71%) in the second, and 72 (65%) in the third round. The highest degree of agreement (95.8%) was reached with the statement that the HCP needs to build a relationship with the patient to influence adherence. A high level of agreement was not reached for statements that morbidity and mortality are influenced by the level of adherence to therapy, and no consensus was reached on the statement that age of the patient influences adherence to treatment. Conclusion: We found that Italian HCPs endorsed a strong relationship with the patient as being a key driver in improving adherence. There were several areas, such as the influence of adherence on morbidity and mortality, where the consensus of Italian HCPs differed from the published literature. These areas require investigation to determine why these discrepancies exist.

OBJECTIVE:A 6-minute walk work (6MWW), that is the product of distance walked at the 6-minute walk test (6MWT) multiplied by body weight, has been suggested as an appropriate variable for estimating functional capacity. Under the hypothesis that 6MWW strongly correlates with expiratory muscle strength (PE max), as found in Chronic Obstructive Pulmonary Disease (COPD), the aim of the study was to determine the degree of this correlation in adults with cystic fibrosis.METHODS:A cross-sectional study was carried out at the Regional Referral Centre for Cystic Fibrosis, where patients with cystic fibrosis attending their regular follow-up, aged 18 years or older with mild-to-normal lung disease, were asked to participate. Dietitians determined nutritional status before subjects performed spirometry and static measurement of respiratory muscles. The 6MWT was performed as the last study procedure. Spearman correlation test was used to correlate PE max with 6MWW and other study variables.RESULTS:Twenty-five cystic fibrosis subjects aged 18-30 years and with FEV1 values ranging from 42.4% to 123.4% predicted completed the study. PE max strongly correlated with 6MWW (rho .72, p = .0001) whereas it did not correlate with other study variables, including distance at the 6MWT. Distance walked multiplied by body weight (p = .0019) and body mass index (p = .0238) were significantly lower in those with PE max below the lower limits of normal.CONCLUSION:Increased functional exercise tolerance is related to higher static expiratory pressure in patients with mild-to-normal cystic fibrosis lung disease. Difference in exercise performance might reflect a possible difference in body composition that needs to be further investigated.

When you walk through the halls of any museum, you usually want to remember as much information as possible. But so often it happens that, when you walk out the front door, you can't remember half of all that you learned or saw. If even adults cannot remember most part of the newly acquired information, you can imagine what happens in the children's heads. School Museum of "Russian Folk Art" located in Zelenograd, Moscow, collected during several years a huge quantity of historical interesting props. As time passed, it became increasingly difficult to conduct educational excursions. In such a context, the idea of an interactive guidebook has come to life. The main goal of this project is to involve all visitors "into the game" and help them remember the main route, interesting objects and useful information. Passing quests, each visitor becomes an active participant in the excursion. Small tasks help memorize more information, develop team skills and fix memorable impressions. In this paper we want to share our experience and methodology in the creation of educational routes in our museum.

of antifungal therapy in CF is unknown.We retrospectively reviewed the outcomes and tolerability of antifungal therapy in adults with CF.Methods: Patients receiving antifungal therapy at our centre from September 2006 to September 2016 were identified.Data were collected from hospital notes and electronic records.Results: 21 patients (12 male, 9 female) received a total of 41 courses of antifungal therapy.Indication for treatment was: ABPA n = 13 (61.9%),Aspergillus bronchitis n = 6 (28.6%),Aspergillus sensitisation n = 1 (4.8%) and Penicillium sp.infection n = 1 (4.8%).20/21 patients (95%) had ≥1 sputum positive for fungi prior to antifungals treatment.Within the ABPA group, 1 patient also had co-infection with Rasamsonia sp. and Exophiala sp while another also isolated Scedosporium sp.Therapy was itraconazole only n = 14; itraconazole followed by voriconazole n = 6; itraconazole, amphotericin B, caspofungin and voriconazole sequentially n = 1.Median length of treatment with itraconazole was 327 days (range 31-1,897).2 patients stopped itraconazole treatment before three months due to alopecia and abdominal pain.Median length of treatment with voriconazole was 89 days (range 31-841). 1 patient stopped voriconazole due to deranged liver function.12/13 patients with ABPA received oral prednisolone prior to antifungals.Mean total IgE at start of antifungals was 1419.6 ku/L (SD 1714.8 ku/L) and 705.4 ku/L (SD 843.4 ku/L) at 3 months ( p = 0.003).Mean Aspergillusspecific IgE fell from 29.1 ku/L (SD 27.5 ku/L) to 21.6 kuA/L (SD 19.6 ku/L) at 3 months ( p = 0.008).Mean Aspergillus precipitins were 3.6 lines (SD 1.9) at baseline and 3.3 lines (SD 2.0) at 3 months ( p = 0.12).Conclusion: Antifungals were well tolerated and associated with improvements in Aspergillus serology.Prospective studies of antifungals in CF are needed.