Current cough and sputum assessed by the cough and sputum assessment-questionnaire (CASA-Q) is associated with quality of life impairment in cystic fibrosis.

BACKGROUND: Cough and sputum are major symptoms in cystic fibrosis (CF) that contribute to the impairment of quality of life. METHODS: This prospective single centre cross-sectional pilot study aimed to evaluate the results of a self-administered questionnaire assessing cough and sputum symptoms (2 domains), and their impact (2 domains) on daily activities in the previous week, named the Cough and Sputum Assessment Questionnaire (CASA-Q) in CF adult patients at stable state, and to analyse associations with clinical, functional, microbiological, radiological data, and two quality of life scales: the Cystic Fibrosis Questionnaire Revised (CFQ-R) and the Saint George Respiratory Questionnaire (SGRQ). RESULTS: Forty-eight patients were included in this analysis (69% men; median age of 27.8 ± 8.1 years; median body mass index of 21.8 + 3.3 kg/m²; mean FEV1 of 64 ± 30% of the predicted value). The mean values of the CASA-Q domains were 58 ± 23 for cough symptoms, 77 ± 24 for cough impact, 62 ± 25 for sputum symptoms and 84 ± 21 for sputum impact. Impairment in CASA-Q cough and sputum domains was associated with dyspnea mMRC scale (p < 0.005 for all 4 domains of CASA-Q) and exacerbations in the previous year (p < 0.05 for CASA-Q symptoms domains). We also found correlations between all domains of the CASA-Q and quality of life questionnaires including SGRQ (p < 0.001) and to a lesser extend CFQ-R. We identified a clinical phenotype (female gender, ΔF508 heterozygous mutation, dyspnea mMRC scale) associated with an impairment of CASA-Q score and quality of life using a 2-step cluster analysis. CONCLUSIONS: CASA-Q allows the assessment of cough and sputum in CF adult patients and is associated with quality of life impairment. This simple easy-to-use tool could be used in routine clinical practice and in clinical studies to assess cough and sputum in CF patients. TRIAL REGISTRATION: The study was registered on ClinicalTrials.gov (NCT02924818, first posted on 5th October 2016).

Daily spirometry in an acute exacerbation of adult cystic fibrosis patients.

To help answer the question of length of intravenous antibiotics during an acute exacerbation of cystic fibrosis (CF), we had subjects to follow daily home spirometry while on intravenous antibiotics. CF patients, 18 and older, with an acute exacerbation requiring intravenous antibiotics had a daily FEV1. The average time to a 10% increase over their initial sick FEV1 was calculated, as well as the time to a new baseline. A total of 25 subjects completed the study. Ten of the 25 subjects did not have a sustainable 10% increase in FEV1. Of the 15 subjects with a sustainable 10% increase in FEV1, it took 5.2 days (±4.5) after day 1, while a new baseline was achieved on average at 6.6 days (±4.8) after day 1. Given the wide range of time to a 10% improvement and new baseline, it is recommended there should be flexibility in length of intravenous antibiotics in CF, not by a preset number.

Polish Cystic Fibrosis Patients' Health-Related Quality of Life and Its Influencing Factors: A Cross-Sectional, Single-Centre Study.

Cystic fibrosis (CF) is a disease characterized by long-term and troublesome symptoms that affect the patient's life. This study aimed to assess and compare the health-related quality of life (HRQoL) of Polish CF patients and identify factors influencing it. The study group consisted of 79 patients (6 to 42 years old), who filled in an age-appropriate Cystic Fibrosis Questionnaire-Revised. Medical data were collected from each patient's medical records. The domains with the highest HRQoL median were eating problems (88.89), digestive symptoms (77.78) and physical functioning (75.00). The lowest-rated domain was social functioning (61.90). Age negatively correlated with eight domains, and most strongly with treatment burden (rho = -0.474). Physical functioning positively correlated with all spirometry parameters, and most strongly with FEV1% (rho = 0.588). Treatment burden, body image and respiratory symptoms were positively correlated with all spirometry parameters except PEF%. Present exacerbations reduced scores in almost all domains, and in the MANCOVA model they were a significant factor differentiating patients' HRQoL. The univariate analysis of MANCOVA showed the significant effects of both health condition (F = 8.32, p = 0.005) and the COVID-19 pandemic (F = 5.89, p = 0.018) on social functioning domain, and of the place of residence on body image (F = 5.60, p = 0.21). A decreasing HRQoL with increasing age and during exacerbations indicates that it is important to focus on these aspects of patients' lives and ensure they received the necessary support from their healthcare providers.

Non-respiratory health-related quality of life in people with cystic fibrosis receiving elexacaftor/tezacaftor/ivacaftor.

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be safe and efficacious in people with cystic fibrosis (CF) heterozygous for F508del and a minimal function mutation (F/MF) or homozygous for F508del (F/F) in two pivotal Phase 3 trials, significantly improving percentage predicted forced expiratory volume in 1 second, Cystic Fibrosis Questionnaire-Revised, Respiratory Domain (CFQ-R RD) scores, and sweat chloride concentration. Here, we analyzed the 11 non-respiratory domains (non-RDs) of the CFQ-R, which assess general health-related quality of life (i.e., Physical Functioning, Role Functioning, Vitality, Health Perceptions, Emotional Functioning, and Social Functioning) and quality of life impacted by CF (i.e., Body Image, Eating Problems, Treatment Burden, Weight, and Digestive Symptoms), for participants in these two Phase 3 trials. ELX/TEZ/IVA treatment led to higher scores in all CFQ-R non-RDs, with improvements in most domains compared with control treatments. These findings demonstrate that ELX/TEZ/IVA improves a range of CF-specific symptoms and general functioning and well-being.

Pulmonary Function Tests in the Evaluation of Early Lung Disease in Cystic Fibrosis.

BACKGROUND: Properly evaluating respiratory system dysfunction is essential in children with cystic fibrosis (CF). This prospective study aimed to assess the course of early lung disease based on multiple breath nitrogen washout (MBNW), impulse oscillometry (IOS), and conventional techniques, such as spirometry and body plethysmography. METHODS: Over a 2 year recruitment period, subjects with CF aged 7-18 performed pulmonary function tests (PFTs). Moreover, the nutritional and microbiological status, frequency of pulmonary exacerbations (PExs), and patients' health-related quality of life (HRQoL) were assessed. RESULTS: The mean age of the children (n = 69) was 14.09 ± 3.26 years; F/M 37/32. Spirometry-based diagnoses of normal lung function (forced expiratory volume in 1 s, FEV1 ≥ 90%pred), mild (FEV1 70-89%pred) and moderate (FEV1 40-69%pred) lung diseases were established in 34 (49.3%), 25 (36.2%), and 10 (14.5%) patients, respectively. An elevated lung clearance index (LCI > 6.98) was observed in 85% of the subjects with normal FEV1. The presence of Pseudomonas aeruginosa infection (n = 16) and the number of PExs treated with IV antibiotics were associated with significantly worse PFT results. CONCLUSIONS: MBNW and IOS are more helpful tools than conventional techniques in assessing early lung disease in CF. LCI is a more useful parameter for detecting functional abnormalities than FEV1 in school-age children.

Health-Related Quality of Life in Adults with Cystic Fibrosis: Familial, Occupational, Social, and Mental Health Predictors.

BACKGROUND: Cystic Fibrosis (CF) adult patients experience daily physical symptoms and disabilities that may impact their quality of life and mental health. METHODS: This prospective study aimed to evaluate the relative contribution of the familial, occupational, and social environment, besides that of the main physical and mental health factors, to the quality of life of CF adult patients using the Cystic Fibrosis Questionnaire-Revised (CFQ-R) in a multivariate model. RESULTS: Fifty patients were analyzed (70% of men; median age of 25 years; median body mass index of 21 kg/m²; median FEV1 of 57%). Anxiety and depression scores were negatively associated with 9 of the 12 CFQ-R domains. When controlling for anxiety and depression, FEV1% and BMI were significant positive predictors of several domains of the CFQ-R. All the familial, occupational, and social components analyzed but one (professional training) were predictors of at least one domain of the CFQ-R. CONCLUSION: Anxiety and depression explained a greater proportion of the variance than physical variables (age, sex, BMI, FEV1%, and exacerbation in the last year) in CF HRQoL. Many familial, occupational, and social components were also specifically and independently predictors of some HRQoL domains. Their screening might help identifying CF patients eligible for specific interventions, focusing on the impaired QoL dimensions.

Use of estrogen supplementation is associated with higher quality of life scores in women with cystic fibrosis.

The association of estrogen supplementation use and quality of life in women with cystic fibrosis (CF) is not well characterized. In this cross-sectional study, women with CF completed quality of life questionnaires during a routine CF clinic visit. The use of estrogen supplementation was associated with higher quality of life scores in all domains of the CF questionnaire-revised (CFQ-R) and was significant in the role limitations and respiratory domains. Most participants who were not currently using estrogen supplementation had previously used estrogen supplementation. Most participants had used estrogen to regulate menses, prevent pregnancy and control symptoms around menses. Use of estrogen supplementation was not associated with differences in life-space mobility or screening for sexual dysfunction. This is the largest study to date investigating the association of estrogen supplementation and quality of life in women with CF. Prospective randomized studies are needed to clarify the association of estrogen supplementation and quality of life in women with CF.

Filamentous fungi in the airway of patients with cystic fibrosis: Just spectators?

BACKGROUND: There are important advances in the management of bacterial infection in patients with cystic fibrosis (CF), but there are many gaps in the field of fungal infections. AIMS: The aim of this study was to analyse whether chronic respiratory filamentous fungal colonization had clinical impact and whether antifungal treatment can change the disease. METHODS: The prospective, bicentric and descriptive study was carried out within a 3-year follow-up period, with four-month periodicity medical controls. Adult patients from two CF units of tertiary hospitals were included. Clinical, microbiological, analytical and spirometric variables were collected. Quality of life was evaluated in a subgroup, using the Spanish version of the Revised Cystic Fibrosis Quality of Life Questionnaire (CFQ-R). To statistically analyze the evolution of forced expiratory along time (volume of air blown out in 1 second -FEV1-) and the forced vital capacity (FVC), mixed linear models were carried out. RESULTS: From the ninety-eight patients under study, 40 suffered chronic filamentous fungal colonization. The presence of filamentous fungi in airway was associated to an annual fall of FEV1 and FVC of 0.029 and 0.017 litres, respectively (p<0.001). In addition, worse quality of life based on CFQ-R, significant when concerning physical condition and emotional state, was also linked with the fungal colonization. Protocolized antifungal therapy, nebulized or oral, improved FEV1 in 0.023 and 0.024 litres per year, respectively (p<0.001). CONCLUSIONS: Chronic filamentous fungal colonization in patients with CF is associated with a significant annual decline of lung function that persists over time. Chronic antifungal therapy slows down this progression, mainly in the patient with more advanced disease.

Antisense oligonucleotide eluforsen is safe and improves respiratory symptoms in F508DEL cystic fibrosis.

BACKGROUND: Eluforsen is an antisense oligonucleotide designed to bind to the mRNA region around the F508-encoding deletion and restore the cystic fibrosis transmembrane conductance regulator (CFTR) protein function in the airway epithelium. We assessed the safety and tolerability, pharmacokinetics and exploratory measures of efficacy of inhaled eluforsen in cystic fibrosis (CF) patients homozygous for the F508del-CFTR mutation. METHODS: This randomised, double-blind, placebo-controlled, dose escalation 1b study recruited adult CF subjects with a FEV1 > 70% predicted in four single ascending dose cohorts and four multiple ascending dose cohorts. Primary objectives were safety and tolerability. Secondary endpoints included pharmacokinetics, percent predicted forced expiratory volume in 1 s (ppFEV1), and Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Symptom Score (RSS). RESULTS: Single and multiple doses of inhaled eluforsen up to 50 mg were safe and well tolerated. A maximum tolerated dose was not established. Systemic exposure was low in all cohorts and lung function remained stable throughout the study. Three of four eluforsen-treated groups in the MAD study demonstrated an improvement in CFQ-R RSS at end of treatment with adjusted mean change from baseline values ranging from 6.4 to 12.7 points. In comparison, there was a mean decrease of 6.5 points in the placebo group from baseline to end of treatment. CONCLUSIONS: Inhaled eluforsen up to 50 mg dosed 3 times per week for 4 weeks was safe and well tolerated, showed low systemic exposure, and demonstrated improvement in CFQ-R RSS, a relevant measure of clinical benefit in CF patients.

Amikacin liposome inhalation suspension for chronic Pseudomonas aeruginosa infection in cystic fibrosis.

BACKGROUND: Shortcomings of inhaled antibiotic treatments for Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) include poor drug penetration, inactivation by sputum, poor efficiency due to protective biofilm, and short residence in the lung. METHODS: Eligible patients with forced expiratory volume in 1 s (FEV1) ≥25% of predicted value at screening and CF with chronic P. aeruginosa infection were randomly assigned to receive 3 treatment cycles (28 days on, 28 days off) of amikacin liposome inhalation suspension (ALIS, 590 mg QD) or tobramycin inhalation solution (TIS, 300 mg BID). The primary endpoint was noninferiority of ALIS vs TIS in change from baseline to day 168 in FEV1 (per-protocol population). Secondary endpoints included change in respiratory symptoms by Cystic Fibrosis Questionnaire-Revised (CFQ-R). RESULTS: The study was conducted February 2012 to September 2013. ALIS was noninferior to TIS (95% CI, -4.95 to 2.34) for relative change in FEV1 (L) from baseline. The mean increases in CFQ-R score from baseline on the Respiratory Symptoms scale suggested clinically meaningful improvement in both arms at the end of treatment in cycle 1 and in the ALIS arm at the end of treatment in cycles 2 and 3; however, the changes were not statistically significant between the 2 treatment arms. Treatment-emergent adverse events (TEAEs) were reported in most patients (ALIS, 84.5%; TIS, 78.8%). Serious TEAEs occurred in 17.6% and 19.9% of patients, respectively; most were hospitalisations for infective pulmonary exacerbation of CF. CONCLUSIONS: Cyclical dosing of once-daily ALIS was noninferior to cyclical twice-daily TIS in improving lung function. ClinicalTrials.gov Identifier: NCT01315678.

The impact of cystic fibrosis-related diabetes on health-related quality of life.

Cystic fibrosis-related diabetes (CFRD) is a well-known comorbidity among the CF population. To investigate whether CFRD impacts health-related quality of life (HRQoL), domain scores from the Cystic Fibrosis Questionnaire-Revised for adolescents and adults over 14 years old (CFQ-R 14+) were compared between CF individuals with CFRD on insulin, CFRD not on insulin, impaired glucose tolerance, and normal blood glucose tolerance. The median score for the Treatment Burden domain was significantly worse for individuals with CFRD on insulin (p < 0.001) compared to the other diagnostic groups, and this association remained significant following adjustment for confounding variables. In conclusion, the additional requirement for insulin significantly contributes to treatment burden in adults with CFRD and therefore novel strategies to reduce treatment burden for this group are urgently needed.

Treatment compliance in cystic fibrosis patients with chronic Pseudomonas aeruginosa infection treated with tobramycin inhalation powder: The FREE study.

BACKGROUND: A high treatment burden with nebulised therapies in cystic fibrosis (CF) patients is the major limitation for treatment compliance; moreover, studies on treatment compliance with inhaled antibiotics are limited. This study assessed compliance to TOBI® Podhaler™ (TIP) treatment in CF patients with chronic Pseudomonas aeruginosa (Pa) infections in a real-world setting using the Italian Treatment Adherence CF Questionnaire (ITA-CFq). METHODS: This longitudinal, multicentre, cohort study included 2 follow-up (FU) visits: FU-1 at 3-months±15-days from the baseline visit and FU-2 at the end of third TIP cycle (or 6-months after enrolment, whichever occurred first). The effect of TIP on quality-of-life (QoL) and treatment satisfaction were evaluated using Cystic Fibrosis Questionnaire-Revised (CFQ-R) and Treatment Satisfaction Questionnaire for Medication (TSQM), respectively. Overall compliance to treatments was assessed using ITA-CFq. RESULTS: Eighty-two patients (mean age, 24.8 ±â€¯7.9 years), including 22 paediatric patients (age, <18 years), were enrolled in the study; 56 (68.3%) patients, including 17 paediatric patients, completed the study. At baseline, the mean compliance score to aerosol antibiotic treatment was 7.8 ±â€¯3.2; upon introducing TIP, the compliance score improved to 9.4 ±â€¯1.2 at the FU-1 and thereafter remained stable at 9.5 ±â€¯1.2. TSQM was higher for the convenience domain (74.2 ±â€¯17.1 at enrolment and slightly improved to 77.8 ±â€¯15.9 at FU-2) following TIP initiation. No substantial effect of TIP was observed on the QoL when measured using the revised CFQ-R. The safety profile was in line with previous findings. CONCLUSION: TIP was convenient to use and led to improved treatment adherence in CF patients with chronic Pa-infection.

Psychometric evaluation of the Swedish translation of the revised Cystic Fibrosis Questionnaire in adults.

AIM: The CFQ-R is one of the most established disease-specific, health-related quality of life (HRQOL) measurements for patients with cystic fibrosis (CF). The aim was to evaluate the psychometric properties of the Swedish translation of CFQ-R in adults. METHOD: A total of 173 CF patients answered the CFQ-R. The CFQ-R was evaluated with regard to: (1) distributional properties; (2) reliability; and (3) construct validity. RESULTS: The majority of scales were negatively skewed with ceiling effects. Eight of the 12 scales had satisfactory homogeneity; 10 of the 12 scales had satisfactory test-retest reliability. On many of the CFQ-R scales expected differences were observed when patients were divided regarding disease severity, nutritional status, age, and gender. CONCLUSION: Some weaknesses were detected, but overall the instrument has satisfactory psychometric properties.

Rationale and design of a randomized trial of home electronic symptom and lung function monitoring to detect cystic fibrosis pulmonary exacerbations: the early intervention in cystic fibrosis exacerbation (eICE) trial.

BACKGROUND: Acute pulmonary exacerbations are central events in the lives of individuals with cystic fibrosis (CF). Pulmonary exacerbations lead to impaired lung function, worse quality of life, and shorter survival. We hypothesized that aggressive early treatment of acute pulmonary exacerbation may improve clinical outcomes. PURPOSE: Describe the rationale of an ongoing trial designed to determine the efficacy of home monitoring of both lung function measurements and symptoms for early detection and subsequent early treatment of acute CF pulmonary exacerbations. STUDY DESIGN: A randomized, non-blinded, multi-center trial in 320 individuals with CF aged 14 years and older. The study compares usual care to a twice a week assessment of home spirometry and CF respiratory symptoms using an electronic device with data transmission to the research personnel to identify and trigger early treatment of CF pulmonary exacerbation. Participants will be enrolled in the study for 12 months. The primary endpoint is change in FEV1 (L) from baseline to 12 months determined by a linear mixed effects model incorporating all quarterly FEV1 measurements. Secondary endpoints include time to first acute protocol-defined pulmonary exacerbation, number of acute pulmonary exacerbations, number of hospitalization days for acute pulmonary exacerbation, time from the end of acute pulmonary exacerbation to onset of subsequent pulmonary exacerbation, change in health related quality of life, change in treatment burden, change in CF respiratory symptoms, and adherence to the study protocol. CONCLUSIONS: This study is a first step in establishing alternative approaches to the care of CF pulmonary exacerbations. We hypothesize that early treatment of pulmonary exacerbations has the potential to slow lung function decline, reduce respiratory symptoms and improve the quality of life for individuals with CF.