Objectives: Spirometry measurement is the gold standard for assessing disease severity in cystic fibrosis (CF). Poor-quality spirometry tests can result in inaccurate measurement of FEV1 and FVC. Manchester Adult CF Centre has transformed from hospital to home-based spirometry testing during COVID-19. Unlike hospital-based spirometry, home-based spirometry relies entirely on the subject to obtain good quality spirometry. Therefore, we sought to ascertain the quality of home-based spirometry and the test errors in our patients. Methods: A convenience sample of adults with CF attending Manchester Adult CF Centre were provided with a NuvoAir home-based spirometer to perform routine lung function between March–October 2020. NuvoAir respiratory platform consists of a mobile phone application, Bluetooth spirometer and an online results portal. The spirometer also provides feedback to patients’ spirometry quality. Initial patient set-up was performed in-hospital or virtually with a member of the CF clinical team. All patient sessions were included irrespective of quality of spirometry test session. Acceptability and repeatability criteria were applied as per NuvoAir software in line with ATS/ERS guidelines, along with assigning a quality grading A–Faccording to ATS/ERS standardised pulmonary function report criteria at time of testing. Results: 66 CF patients (32 female) mean age 31.3 (18–55) performed 343 spirometry sessions totaling 1,041 individual spirometry tests with a NuvoAir device were graded as follows: Grade A = 30.3%, Grade B = 36.2%, Grade C = 3.5%, Grade D = 2.6%, Grade E = 16.6%, Grade F = 10.8%. Further analysis of all 1,041 tests for common errors indicated BX – Back extrapolation 2%, TP- Time to Peak (slow start) 14.6%, CO – Cough 1.4%, ET – Early termination 0.5%, CE – Cessation or glottic closure 12.9%. Overall, general tests A–C considered usable was 70%. Conclusion: The results show good-quality standards can be achieved through home-based spirometry.

Aim: Evaluated etiological factors that cause lung infections in cystic fibrosis (CF) patients and how these pathogens affected lung function.Methods: We performed sputum examination in 80 patients with CF (aged from 3 months to 40 years) and spirometric examination in 34 of these patients (aged from 5 to 40 years), of clinical and bacteriological monitoring at the Cystic Fibrosis Center in Republic of Moldova.The research found an expected correlation between identified germs and FVC and FEV 1 values.Results: The study remark the presence of pulmonary infections with P. aeruginosa in 73.8% of cases (60 patients), S.aureus -57.5% (46 patients), St. maltophylia -3.75% (3 patients), ABPA -35.83% (22 patients) and B. cepacia -1.66% (1 patient each).Studying the correlation between spirometric values and bronchial culture results showed that FVC and FEV 1 values depend on the pathogen isolated.Thus spirometric values for patients with pulmonary infection with P. aeruginosa (n = 22) are FVC -75.31 ± 1.36%, FEV 1 -72.31 ± 1.47%, in infection with S.aureus (n = 20) lung function indices are significant ( p < 0.05) increase: FVC -80.25 ± 1.41%, FEV 1 -76.8 ± 1.56%.Patients with St. maltophylia pulmonary infection (n = 3) showed spirometric indices with FVC values -70.33 ± 9.40% ( p < 0.05) and FEV 1 -69.66 ± 13.23% ( p < 0.05) and in pulmonary infection with ABPA respiratory function indices are below the reference values (FVC -56.2 ± 5.3%, FEV 1 -53.9 ± 6.1%).Conclusion: P. aeruginosa is a microorganism that most often causes chronic lung infections in CF patients.Infections with Aspergillus fumigatus, P. aeruginosa and St. maltophylia shows a marked deterioration in lung function, recording the lowest spirometric values compared to other pathogens.

Aim: Evaluated etiological factors that cause lung infections in cystic fibrosis (CF) patients and how these pathogens affected lung function.Methods: We performed sputum examination in 80 patients with CF (aged from 3 months to 40 years) and spirometric examination in 34 of these patients (aged from 5 to 40 years), of clinical and bacteriological monitoring at the Cystic Fibrosis Center in Republic of Moldova.The research found an expected correlation between identified germs and FVC and FEV 1 values.Results: The study remark the presence of pulmonary infections with P. aeruginosa in 73.8% of cases (60 patients), S.aureus -57.5% (46 patients), St. maltophylia -3.75% (3 patients), ABPA -35.83% (22 patients) and B. cepacia -1.66% (1 patient each).Studying the correlation between spirometric values and bronchial culture results showed that FVC and FEV 1 values depend on the pathogen isolated.Thus spirometric values for patients with pulmonary infection with P. aeruginosa (n = 22) are FVC -75.31 ± 1.36%, FEV 1 -72.31 ± 1.47%, in infection with S.aureus (n = 20) lung function indices are significant ( p < 0.05) increase: FVC -80.25 ± 1.41%, FEV 1 -76.8 ± 1.56%.Patients with St. maltophylia pulmonary infection (n = 3) showed spirometric indices with FVC values -70.33 ± 9.40% ( p < 0.05) and FEV 1 -69.66 ± 13.23% ( p < 0.05) and in pulmonary infection with ABPA respiratory function indices are below the reference values (FVC -56.2 ± 5.3%, FEV 1 -53.9 ± 6.1%).Conclusion: P. aeruginosa is a microorganism that most often causes chronic lung infections in CF patients.Infections with Aspergillus fumigatus, P. aeruginosa and St. maltophylia shows a marked deterioration in lung function, recording the lowest spirometric values compared to other pathogens.

Background: There are few data on young people’s own experiences of transferring from paediatric to adult care, or readiness to self-manage care. Methods: A total of 132 young people living with perinatal HIV, aged 14–25 years, answered questions about transition experiences. Results: Of the participants, 45 (34%), with a median age of 16 (interquartile range [IQR] 16–17), were in paediatric care, of whom 89% reported that transition discussions had begun, at median age 15 (IQR 14–16) years. Young people in adult care were more likely than those in paediatric care to self manage appointments (90% vs 42% respectively, P < 0.001), and know their antiretroviral therapy (ART) drugs (55% vs 37%, P = 0.033). Knowledge of most recent CD4 T cell count/VL was slightly better for those in adult care (48% vs 31%, P = 0.059); naming side effects of ART was similar (71% vs 60%, P = 0.119). Conclusions: Transition discussions occurred before movement from paediatric to adult care. Further education around ART, potential side effects, and CD4 T cell count/viral load knowledge is required.

during the year from 6,1 ± 1,9 to 3,6 ± 1,1 ( p < 0,001), while in group2 no significant change was seen.

Introduction Cystic fibrosis (CF) is a life limiting genetic condition which occurs due to mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). Absence of functional CFTR protein leads to progressive respiratory disease characterized by bronchiectasis and chronic infections. CF lung disease predisposes patients to infection and sensitivity to the fungal pathogen Aspergillus fumigatus. Novel CFTR modulating therapies have recently been associated with potential disease modification in CF. It is unclear whether these therapies will have an influence on susceptibility to Aspergillus related disease in CF. Methods We conducted a retrospective cohort study examining patients who commenced the CFTR modulator ivacaftor. Over a period of 5 years we monitored the isolation ofAspergillus in sputum samples and patients' serological response to Aspergillus fumigatus. Results In 40 patients, ivacaftor therapy resulted in a significant decrease in sweat chloride (from 112 [102.75 – 119.25] to 45 [37 – 61], p<0.001), and an increase in FEV1 from 53.2% to 63.1% predicted. One patient was treated both with CFTR modulators and itraconazole for ABPA. There was a significant decrease in the number of sputum samples patients provided in the year preivacaftor initiation compared to 5 years post from a median of 7 [4 – 12.75] per year to 1 [0 – 4], p<0.001. There was no difference in the rate of Aspergillus isolation in sputum. There was an early decrease (at 6 months) in total IgE levels from 35.55 [15.9 – 202.5] to 26.7 [9.5 – 108.25] (p=0.02) but these were not sustained over longer periods. There were no significant changes in Aspergillus specific IgE or IgG over the study time. Conclusion Effective CFTR modulation in patients with CF does not appear to alter susceptibility or reaction to Aspergillus fumigatus in clinical settings. These findings suggest that Aspergillus will remain a significant pathogen in a new era of CF when most patients will receive CFTR modulator therapy. This will potentially result in clinical challenges due to difficult drug-drug interactions between –azole medications and CFTR modulators.

biomass of pre-formed static biofilms, in a dose dependent manner.CLSM measurements showed within 10 minutes, 200 μg/ml PAAG removed greater than 60% of the bacteria and more than 90% of the bacteria within the biofilm within 1 hour of treatment.PAAG also works in a synergistic manner with antibiotics such as tobramycin and meropenem to reduce their MIC.Conclusion: PAAG, a polycationic glycopolymer, effectively disrupts recalcitrant biofilms formed by clinically relevant Bcc.Further, this molecule synergizes commonly used antibiotics, thereby increasing the effective arsenal for Bcc treatment.Together with its mucolytic capacity, PAAG's anti-biofilm and antibiotic potentiation activities hold great promise for clinically-translatable Bcc therapy.

Integrin-mediated adhesion to the extracellular matrix involves a surprisingly large number of intracellular proteins, the integrin-associated proteins (IAPs), which are a fraction of the total integrin adhesome. In this review we discuss how genetic approaches have improved our understanding of how each IAP contributes to integrin function, especially in the context of building a functional organism during development. We then begin the process of assembling IAP roles together into an integrated mechanism.

We use the myotendinous junction of Drosophila flight muscles to explore why many integrin associated proteins (IAPs) are needed and how their function is coordinated. These muscles revealed new functions for IAPs not required for viability: Focal Adhesion Kinase (FAK), RSU1, tensin and vinculin. Genetic interactions demonstrated a balance between positive and negative activities, with vinculin and tensin positively regulating adhesion, while FAK inhibits elevation of integrin activity by tensin, and RSU1 keeps PINCH activity in check. The molecular composition of myofibril termini resolves into 4 distinct layers, one of which is built by a mechanotransduction cascade: vinculin facilitates mechanical opening of filamin, which works with the Arp2/3 activator WASH to build an actin-rich layer positioned between integrins and the first sarcomere. Thus, integration of IAP activity is needed to build the complex architecture of the myotendinous junction, linking the membrane anchor to the sarcomere.

SummaryThis study aimed to determine prevalence of Ralstonia spp. in cystic fibrosis patients, look for any evidence of cross infection and to describe clinical outcomes for patients infected by Ralstonia spp. Prevalence of Ralstonia spp. was calculated annually from 2008 to 2016. Pulsed-field gel electrophoresis was performed on ⩾1 sample from patients with an isolation of Ralstonia spp. between 2008 and 2016. A prospective, longitudinal observational study of adult patients was performed with 12 months follow-up from recruitment. Prevalence of Ralstonia spp. rose from 0·6% in 2008 to 2·4% in 2016. In total 12 out of 14 (86%) patients with ⩾1 isolation of Ralstonia spp. developed chronic infection. A pair and a group of three unrelated patients with epidemiological connections shared strains of Ralstonia mannitolilytica. Lung function of Ralstonia spp. infected patients was moderately to severely impaired. Prevalence of Ralstonia spp. is low but increasing. The risk of a patient developing chronic Ralstonia spp. infection following first acquisition is high and cross-infection may be possible. Whether Ralstonia spp. infection causes increased pulmonary exacerbation frequency and lung function decline needs to be evaluated in larger prospective studies.

Vinculin is a highly conserved protein involved in cell adhesion and mechanotransduction, and both gain and loss of its activity causes defective cell behaviour. Here, we examine how altering vinculin activity perturbs integrin function within the context of Drosophila development. Whereas loss of vinculin produced relatively minor phenotypes, gain of vinculin activity, through a loss of head-tail autoinhibition, caused lethality. The minimal domain capable of inducing lethality is the talin-binding D1 domain, and this appears to require talin-binding activity, as lethality was suppressed by competition with single vinculin-binding sites from talin. Activated Drosophila vinculin triggered the formation of cytoplasmic adhesion complexes through the rod of talin, but independently of integrin. These complexes contain a subset of adhesion proteins but no longer link the membrane to actin. The negative effects of hyperactive vinculin were segregated into morphogenetic defects caused by its whole head domain and lethality caused by its D1 domain. These findings demonstrate the crucial importance of the tight control of the activity of vinculin.