Standards of care and educational gaps in adult cystic fibrosis units: a European Respiratory Society survey.

Background: Significant progress in the field of cystic fibrosis (CF) has substantially extended the life expectancy of patients with CF (pwCF). Consequently, the population of adult pwCF has outnumbered paediatric patients in most developed countries. Ageing is a new factor that can contribute to disease complexity and can require adaptation of CF units. Therefore, the necessity for standardised, specialised and multidisciplinary care is imperative. Concerns arise regarding the adequacy of current healthcare, therapeutic and educational offerings. Methods: To address these concerns, a multinational survey was conducted to assess the current state of care in specialised multidisciplinary adult and paediatric CF units and identify areas for improvement. Responses were collected from 44 centres providing regular care to CF patients. Results: The survey unveiled considerable disparities in the availability of critical resources, including diagnostic access, supplementary testing, treatment modalities, transplant and transition programmes, and healthcare professionals' training. Conclusion: This study underscores the urgent need to standardise care across these centres in order to minimise disparities in terms of available resources and training with a particular emphasis on adult pwCF who are becoming more numerous and showing different needs with ageing. The changing landscape of CF in adulthood will require constant monitoring to ensure proper adaptation of the current model of care.

Inhaled aztreonam lysine in the management of Pseudomonas aeruginosa in patients with cystic fibrosis: real-life effectiveness.

BACKGROUND: Inhaled antibiotics have achieved or stabilised the clinical condition of patients with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa infection. We aimed to determine the effectiveness of aztreonam lysine inhaled solution (AZLI) in patients with CF and chronic P. aeruginosa infection. METHODS: A retrospective observational study was conducted on patients with CF and chronic P. aeruginosa infection who received AZLI between July 2012 and September 2018 inclusive in three Spanish hospitals in a routine clinical practice setting. The primary endpoint was the absolute change in the percentage of predicted forced expiratory volume in 1 second (FEV1) compared with the previous 12 months, at the start of AZLI treatment and 12 months after starting the drug. Other variables analysed were exacerbations, hospitalisations, type and route of antibiotics prescribed, weight and body mass index (BMI) and adverse drug reactions. RESULTS: In a cohort of 52 patients, AZLI treatment led to stabilisation of FEV1, changing from a mean (SD) value of 55.60 (21.3)% at the start of treatment to 56.8 (20.4)% after 12 months of treatment (p=0.5296) in patients who had not previously received the drug. In addition, it significantly reduced exacerbations from a median (P25; P75) of 2.0 (1.0; 3.0) in the 12 months prior to AZLI to 1.0 (1.0; 2.0) in the 12 months after treatment initiation (p=0.0350). AZLI also reduced the need for other antibiotics and prevented a decrease in BMI, with an adequate safety profile. CONCLUSIONS: AZLI achieved stabilisation of lung function measured by FEV1 in patients with CF and chronic P. aeruginosa infection, along with an adequate safety profile.

Experience With Elexacaftor/Tezacaftor/Ivacaftor in Patients With Cystic Fibrosis and Advanced Disease.

INTRODUCTION: Elexacaftor/tezacaftor/ivacaftor (ETI) was used through the early access programme in Spain from December 2019 in cystic fibrosis (CF) patients with homozygous or heterozygous F508del mutation with advanced lung disease. METHODOLOGY: Multicentre, ambispective, observational, study in which 114 patients in follow-up in 16 national CF units were recruited. Clinical data, functional tests, nutritional parameters, quality of life questionnaires, microbiological isolates, number of exacerbations, antibiotic treatments and side effects were collected. The study also compared patients with homozygous and heterozygous F508del mutations. RESULTS: Of the 114 patients, 85 (74.6%) were heterozygous for F508del mutation, and the mean age was 32.2±9.96 years. After 30 months of treatment, lung function measured by FEV1% showed improvement from 37.5 to 48.6 (p<0.001), BMI increased from 20.5 to 22.3 (p<0.001), and all isolated microorganisms decreased significantly. The total number of exacerbations was also significantly reduced from 3.9 (±2.9) to 0.9 (±1.1) (p<0.001). All items in the CFQ-R questionnaire showed improvement, except for the digestive domain. Oxygen therapy use decreased by 40%, and only 20% of patients referred for lung transplantation remained on the active transplant list. ETI was well-tolerated, with only 4 patients discontinuing treatment due to hypertransaminemia. CONCLUSIONS: ETI decreases the number of exacerbations, increases lung function and nutritional parameters, decrease in all isolated microorganisms, for 30 months of treatment. There is an improvement in the CFQ-R questionnaire score except for the digestive item. It is a safe and well-tolerated drug.

Geographic distribution and phenotype of European people with cystic fibrosis carrying A1006E mutation.

BACKGROUND: A1006E is a Cystic Fibrosis (CF) mutation that is still not widely known. We report phenotypic features and geographic distribution of the largest cohort of people with CF (pwCF) carrying A1006E to date. METHODS: Study of European pwCF carrying A1006E mutation, included in the European CF Society Patient Registry (ECFSPR). Genotype, ancestries and all variables recorded were compared to a cohort of F508del/F508del patients. Rate of decline in percentage-of-predicted FEV1 (ppFEV1) was also analyzed using the 2010-2017 ECFSPR. RESULTS: 44 pwCF carrying A1006E were reported (59% males), median age 33 years old (3-58), 54.5% Spanish and 40.9% Italian, most with ancestry in Murcia (Spain) and Lazio (Italy) regions. Compared to F508del homozygous, A1006E-pwCF were significantly older (75% vs. 52.5% ≥ 18 years old) and diagnosed at later median age (6.98 vs. 0.29 years); showed lower rates of meconium ileus (2.33% vs. 17.7%), pancreatic insufficiency (27.91% vs. 99.26%), diabetes (2.33% vs. 21.98%), liver disease (6.98% vs. 36.72%) and Pseudomonas aeruginosa chronic colonization (30.95% vs. 42.51%); and presented better nutrition (BMI z-score 0.44 vs. -0.43) and ppFEV1 (90.8% vs. 78.6%), with 18.9% (most >40 years old) having a ppFEV1<70%. Additional ppFEV1 decline (0.96% per year) was attributed to F508del/F508del genotype (p = 0.0007). None died or needed organ transplantation during the study period. CONCLUSIONS: A1006E-pwCF are mainly of Western Mediterranean Spanish and Italian descent. When compared with F508del/F508del-pwCF, they usually have a milder form of the disease, associated with pancreatic sufficiency and slower FEV1 decline. However, some will develop progressive respiratory impairment during adulthood.

Impact of SARS-CoV-2 infection in patients with cystic fibrosis in Spain: Incidence and results of the national CF-COVID19-Spain survey.

BACKGROUND: Given the high incidence of confirmed infection by SARS-CoV-2 and mortality by COVID-19 in the Spanish population, its impact was analysed among persons with Cystic Fibrosis (CF) as a group at risk of a worse evolution. The possible causes of the incidence observed in them are explained and how CF Units have faced this health challenge is detailed. METHODS: Retrospective descriptive observational study, for which a Spanish CF Patients with Confirmed COVID-19 Registry is created, requesting information on number of people affected between 8 March-16 May 2020 and their clinical-demographic characteristics from the CF Units participating in the European Cystic Fibrosis Society Patient Registry (ECFSPR). The accumulated incidence is calculated, compared with that of the general population. Additionally, a survey (CF-COVID19-Spain) is carried out on prevention of SARS-CoV-2 infection, workings of CF Units and possible reasons for the incidence observed. RESULTS: COVID-19 was diagnosed in eight CF patients, one of whom had received a lung transplant. The accumulated incidence was 32/10000 in CF patients and 49/10000 in the general population. General death rate was 5.85/10000 while no CF patients included in the ECFSPR died. The characteristics of those affected and the results of the survey are described. CONCLUSIONS: Despite being considered a disease at high risk of severe COVID-19, the low incidence and mortality in CF patients in Spain contrasts with the figures for the general population. The possible factors that would explain such findings are discussed, with the help of the results of the CF-COVID19-Spain survey.