Alan R Smyth’s research while affiliated with Queen's University Belfast and other places

... Although ETI has only been available since 2019, studies have shown that the Pa bacterial load decreases overall but remains at detectable levels (>10 2 ) following the initiation of ETI therapy [33][34][35][36]. Recent studies post-ETI have shown that the colony-forming units of Pa in sputum are lowered 10-fold when compared to ivacaftor alone [37]. ...

Reference:

Highly Effective Modulator Therapy: Implications for the Microbial Landscape in Cystic Fibrosis

... In a large observational US study in pwCF aged 12 years and above, there was no change in pancreatic insufficiency 6 months after ETI treatment [51]. In analyses of the US and UK registries, there was a decline in the use of pancreatic enzyme replacement therapy after ivacaftor licensing in the US CF population, but these results were not replicated in the UK CF population [52]. Longitudinal and large studies in pwCF on ETI are needed to evaluate the possible effects of CFTR modulators on exocrine pancreatic function and requirements of pancreatic enzyme replacement therapy. ...

Reference:

New drugs, new challenges in cystic fibrosis care

... The improvements of survival in CF have been accompanied by an increasing treatment burden, with treatment regimens often including 10-15 drugs and 2-3 h daily devoted to routine therapies [4]. Frequently used drug therapies include airway medications, gastrointestinal therapies, antibiotics and endocrine medications [5]. ...

Reference:

Impact of elexacaftor/tezacaftor/ivacaftor on utilization of routine therapies in cystic fibrosis: Danish nationwide register study

... Physical activity is broadly defined as any bodily movement requiring energy expenditure, whilst exercise is a structured, purposeful subcomponent of physical activity, typically involving aerobic and/or resistance training; both currently recommended standard clinical care for pwCF. 2 ExACT, however, is distinct from both physical activity and general exercise. Developed through close collaboration with the CF community, 3 ExACT is a bespoke exercise-based intervention, 3,4 consisting of aerobic activity with vibration, that must be undertaken at a certain intensity, and specifically incorporates assessment breaths, huffs, and coughs to maximise airway clearance. ...

Reference:

Exercise as an airway clearance technique (ExACT) is not simply physical activity

... E-cigarette vapor contains particulates, solvents, and flavorings that may negatively impact the delicate respiratory epithelium, especially during development. Use of e-cigarettes has been associated with increased cough, asthma exacerbations, and fibrosis markers in some studies (Addissouky et al. 2023a;Song et al. 2023;White et al. 2023). ...

Reference:

Oxidative stress and inflammation: elucidating mechanisms of smoking-attributable pathology for therapeutic targeting

... Our agile, evidence-based methodology for constructing statements and gaining consensus in a timely manner are described in detail in previous papers in this series [1][2][3]. Briefly, the multidisciplinary core committee created the framework for the 4-paper series, and invited authors to contribute short narrative sections and more directive statements. The field of CF is changing rapidly. ...

Reference:

Standards for the care of people with cystic fibrosis (CF); Planning for a longer life

... [47][48][49] The relevance of the study is that new evidence on the role of different probiotics, prebiotics and their synbiotic combinations on CF gut dysbiosis has been generated, in an emerging study field where scarce or null knowledge is available. 50,51 The new findings are to be interpreted with caution as the study was carried out in an in vitro setting. Besides, we acknowledge the limitation of the colonic fermentation model, which despite being adapted to the CF intestinal conditions, might not be fully representative of a CF colon. ...

Reference:

In vitro screening of the impact of dietary prebiotic components, probiotic strains, and their symbiotic combinations on colonic microbiota in children with cystic fibrosis

... Previous studies investigating CFTR modulators and microbiota within the gastrointestinal tract have been mostly limited to Ivacaftor [15][16][17][18] and a couple of dual-modulator studies [17], including our previous work investigating the impact of Tezacaftor/Ivacaftor [19]. With respect to the microbiota structure, previous findings vary across studies incorporating different modulators, patient demographics, and treatment lengths [15][16][17][18]. ...

Reference:

WS09.01 Impact of long-term elexacaftor/tezacaftor/ivacaftor therapy on lung infection microbiota in adults with cystic fibrosis

... © questionnaires were collected previous to ETI initiation and n=156 during ETI therapy, which, throughout the entire observation time frame, resulted in a median of 6 questionnaires (IQR: 4, 7) per patient. [14,24] years; min, max: 12, 55 years), i.e. two per patient: one before and one after the start of ETI (8). Effects of ETI on CFAbd-Score.kid in cwCF aged 6-11 ...

Reference:

The novel CFAbd-Score.kid© reveals a significant decline of abdominal symptoms in children with Cystic fibrosis aged 6 through 11 years on Elexacaftor/Tezacaftor/Ivacaftor — first results

... On top of these new challenges, classic challenges regarding antibiotic therapy persist : selection of antibiotic-resistant bacteria, adverse events with tissue or organ damage,and lack of microbial selectivity and therefore unwanted effect on bronchial and digestive microbiota 27 . New techniques for the detection of lung infectious diseases,better management of antibiotic adverse effect and simplification of treatment burden are 3 of the top 10 updated priorities highlighted by the James Lind Alliance in order to help clinicians take on the new therapeutic challenges raised by the HEMT era 28 . ...

Reference:

One year of ETI reduces lung bacterial colonisation in adults with cystic fibrosis