Perceived burden of respiratory physiotherapy in people with cystic fibrosis taking elexacaftor-tezacaftor-ivacaftor combination: a 1-year observational study.

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.

Understanding the challenges of respiratory physiotherapy in individuals with cystic fibrosis using triple therapy: a one-year study.In order to slow down the progression of their disease, people with cystic fibrosis typically do daily respiratory physiotherapy, which they find to be the most challenging part of managing their condition. The elexacaftor-tezacaftor-ivacaftor combination has changed how they manage their respiratory health. We wanted to see how the perceived difficulty of the treatment changed over one year of using elexacaftor-tezacaftor-ivacaftor. We gave questionnaires to people with cystic fibrosis and to their caregivers before they started the triple therapy and again at 6-12 months. We also used two international questionnaires to learn about symptoms and social limitations related to the disease. The International Physical Activity Questionnaire helped us understand their physical activity levels. We used statistical models to see if the time spent on respiratory physiotherapy changed over the year. Our study involved 47 individuals with cystic fibrosis, with an average age of 21 years, who completed one year of elexacaftor-tezacaftor-ivacaftor therapy. After 6 months, time spent on aerosol therapy decreased by 2.5 minutes per day, time on airway clearance therapies decreased by 8.8 minutes per day, and time for cleaning respiratory equipment decreased by 10.6 minutes per day. By the end of the year, they were saving almost 15 minutes per day on average. At one year, 5 out of 47 said they had stopped using the positive expiratory pressure mask. People with cystic fibrosis using elexacaftor-tezacaftor-ivacaftor may find that they spend less time on their daily respiratory physiotherapy routine. However, activities like aerosol therapy, airway clearance therapies, and maintaining respiratory equipment were still seen as time-consuming.

Short-term effects of positive expiratory pressure mask on ventilation inhomogeneity in children with cystic fibrosis: A randomized, sham-controlled crossover study.

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 (Sacin*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 cmH20) or a sham (<5 cmH20) 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 Sacin*VT mean difference between the standard and the sham procedure was -0.015 (90% confidence interval [CI]: -∞ to 0.025) L-1. There was no statistically significant difference in Scond*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 Sacin*VT with pressure range 10-15 cmH20. 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.

Limitations of the dichotomized 6-minute walk distance when computing lung allocation score for cystic fibrosis: a 16-year retrospective cohort study.

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.

Time Free From Hospitalization in Children and Adolescents With Cystic Fibrosis: Findings From FEV1, Lung Clearance Index and Peak Work Rate.

Background: An 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. Methods: This 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. Results: Over 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. Conclusion: Maintaining 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.

Lung clearance index to characterize clinical phenotypes of children and adolescents with cystic fibrosis.

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.

Prevalence and factors associated with urinary incontinence in females with cystic fibrosis: An Italian single-center cross-sectional analysis.

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.

Remote support by multidisciplinary teams: A crucial means to cope with the psychological impact of the SARS-COV-2 pandemic on patients with cystic fibrosis and inflammatory bowel disease in Lombardia.

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.

Home physiotherapists assisting follow-up treatment in cystic fibrosis: a multicenter observational study.

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.

Exercise capacity and ventilation inhomogeneity in cystic fibrosis: A cross-sectional study.

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.

Delphi poll to assess consensus on issues influencing long-term adherence to treatments in cystic fibrosis among Italian health care professionals.

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.

Expiratory muscle strength and functional exercise tolerance in adults with cystic fibrosis: a cross-sectional study.

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.

Ventilatory limitation and dynamic hyperinflation during exercise testing in Cystic Fibrosis.

OBJECTIVE: To investigate the presence of dynamic hyperinflation after the Modified Shuttle Test (MST) and its relationship with lung function, exercise tolerance, and clinical symptoms in Cystic Fibrosis (CF). METHODS: Retrospective observational study. Subjects in clinically stable condition with a CF diagnosis based on a positive sweat test (chloride >60 mEq/L) and/or presence of two disease causing mutations, with available data on MST, spirometry, maximal voluntary ventilation, and inspiratory capacity manoeuvres were considered for the analysis. Breathing reserve was calculated and a threshold value of 0.7 was subsequently chosen as a value of pulmonary mechanical limit. Subjects were then categorized into two groups according to the change in the inspiratory capacity from rest to peak exercise. Unconditional logistic regression was used to estimate unadjusted odds ratios, 95% confidence intervals and P-values. RESULTS: Twenty-two subjects demonstrated evidence of dynamic hyperinflation during the MST. Thirteen out of 22 subjects were ventilatory limited during exercise including 5 of those without evidence of dynamic hyperinflation (P = 0.24). No combination of variables resulted in a parsimonious regression model. CONCLUSIONS: Dynamic hyperinflation is common in CF and it is not associated with traditionally defined ventilatory limitation parameters during the MST. Pediatr Pulmonol. 2017;52:29-33. © 2016 Wiley Periodicals, Inc.

Pilot Randomized Controlled Trial Evaluating the Effect of Hypertonic Saline With and Without Hyaluronic Acid in Reducing Inflammation in Cystic Fibrosis.

BACKGROUND: Hypertonic saline (HS) has been established as a therapy aimed at restoring the surface liquid of airways liquid and enhancing mucociliary clearance in patients with cystic fibrosis (CF). A formula containing 7% HS and 0.1% hyaluronic acid (HA) is also available, basing its use on the protective effects of HA against elastin injury and on its greater ease of administration (i.e., the perceived acceptability of inhalation). This study explores the effect of HA+HS in reducing the inflammation of airways, by measuring cytokine levels in sputum, its safety profile, and the prevalence of commonly reported symptoms like cough, throat irritation, and saltiness. METHODS: In a pilot, double-blind, randomized controlled, parallel-group, 1:1 trial, clinically stable CF patients older than 6 years of age and with a FEV1pred. >40% were randomized to one of the treatment arms, HS or HS+HA, to be administered twice a day at home. Clinical data, inflammatory markers (IL-1ß, IL-6, IL-8, IL-10, TNF-α, VEGF) in sputum, and judgments on the tolerability and pleasantness were collected at the beginning and after 28 days. RESULTS: HA+HS had no significant effect on inflammatory markers versus HS alone, as shown by broad confidence intervals. In the HS+HA group, the highest decrement from baseline values was observed for IL-1ß (-58.8%) followed by VEGF (-49.9%), whereas in the HS group a significant increment of IL-10 levels (+83.0%; p = 0.011) was the only significant finding. Prevalence of unfavorable scores was 36.8% in HA+HS versus 55% in HS group (p = 0.207); no significant differences were detected in the prevalence of moderate/severe symptoms of cough, saltiness, and throat irritation in pulmonary functions tests after 28 days. CONCLUSIONS: HS+HA administration in CF patients does not show any significant effects on lung inflammation and function as compared to HS alone.

Aerosol delivery practice in Italian Cystic Fibrosis centres: a national survey.

BACKGROUND: Physiotherapists (PTs) are ideally positioned to assist patients and families with inhalation therapies through monitoring, communication and education about available therapies and their proper use; indeed aerosoltherapy management is listed as part of Italian PTs' core competence and in the core syllabus for post-graduate training in respiratory physiotherapy. The aim of this study was to outline the involvement of Italian PTs working in Cystic Fibrosis (CF) centres in the aerosol delivery practice. METHODS: Physiotherapist coordinators (n = 29) of all Italian CF centres were invited to participate in a cross-sectional survey and a semi-structured questionnaire was developed and sent by e-mail. RESULTS: A response rate of 69 % was achieved. The majority of participants were woman and the overall mean professional experience was twenty years. Italian PTs are involved in the aerosol delivery practice, managing education, drug-device combination, dilution and mixing of drugs. CONCLUSIONS: Physiotherapists play a key role in the care of Italian CF patients; nevertheless the Italian Group of Physiotherapists might plan interventions to harmonize the aerosol delivery practice in Italian CF centres and to sustain continuing education.

Isocapnic hyperpnea with a portable device in Cystic Fibrosis: an agreement study between two different set-up modalities.

To evaluate the bias and precision of the respiratory muscle training device formulas to predict respiratory minute volume (RMV) and volume of the reservoir bag (BV) on a cohort of subjects with Cystic Fibrosis (CF). CF patients with available pulmonary function tests and maximal voluntary manoeuvres were included in the study. Vital capacity and maximal voluntary ventilation were extracted from subjects' records and then inserted to the manufacturer's formulas to obtain RMV and BV (measured setting). RMV and BV were compared according to standard and measured formulas in males and females. Sample was described and then processed using Bland-Altman analysis. Bland-Altman analysis for RMV revealed a bias and precision of 8.8 ± 29 L/min in males and 28.8 ± 16 L/min in females; 0.4 ± 0.5 L in males and 0.7 ± 0.4 L in females for BV. Concordance correlation coefficients for RMV were -0.03 in males and 0.02 in females; 0.22 in males and 0.03 in females for BV, reinforcing an unsatisfactory concordance between measured and manufacturer setting. This study shows considerable discrepancies between the two methods, making the degree of agreement not clinically acceptable. This might cause inappropriate setting and disservice to patients with CF.