Feedback controlled photolytic gas phase nitric oxide delivery from S-nitrosothiol-doped silicone rubber films.

J Control Release. 2019 Nov 25;:

Authors: Lautner G, Lautner-Csorba O, Stringer B, Meyerhoff ME, Schwendeman SP

Abstract
Constant therapeutic gas phase nitric oxide (NO) delivery is achieved from S-nitrosothiol (RSNO) type NO donor doped silicone rubber films using feedback-controlled photolysis. For photo-release of the NO gas, the intensity of the LED light source is controlled via a PID (proportional-integral-derivative) controller implemented on a microcontroller. The NO concentration within the emitted gas phase is monitored continuously with a commercial amperometric NO gas sensor. NO release was accurately adjustable up to 10 ppm across a broad range of setpoints with response times of roughly 1 min or less. When NO is generated into an air recipient stream, lower NO yields and a comparable level of toxic nitrogen dioxide (NO2) formation is observed. However, NO gas generated into an N2 recipient gas stream can be blended into pure O2 with very low NO2 formation. Following scale-up, this technology could be used for point-of-care gas phase NO generation as an alternative for currently used gas cylinder technology for treatment of health conditions where inhaled NO is beneficial, such as pulmonary hypertension, hypoxemia, and cystic fibrosis.

PMID: 31778741 [PubMed - as supplied by publisher]

Protein Misfolding and ER stress in Chronic Lung Disease: Will Cell-Specific Targeting be the Key to the Cure?

Chest. 2019 Nov 25;:

Authors: Naiel S, Tat V, Padwal M, Vierhout M, Mekhael O, Yousof T, Ayoub A, Abed S, Dvorkin-Gheva A, Ask K

Abstract
Chronic lung disease accounts for a significant global burden with respect to death, disability and healthcare costs. Due to the heterogeneous nature and limited treatment options for these diseases, it is imperative that the cellular and molecular mechanisms underlying the disease pathophysiology are further understood. The lung is a complex organ with a diverse cell population, and each cell type will likely have different roles in disease initiation, progression and resolution. The effectiveness of a given therapeutic agent may depend on the net effect on each of these cell types. Over the past decade, it has been established that endoplasmic reticulum stress and the unfolded protein response are involved in the development of several chronic lung diseases. These conserved cellular pathways are important for maintaining cellular proteostasis, but their aberrant activation can result in pathology. This review will discuss the current understanding of endoplasmic reticulum stress and the unfolded protein response at the cellular level in the development and progression of various chronic lung diseases. We highlight the need for increased understanding of the specific cellular contributions of UPR activation to these pathologies and suggest that the development of cell-specific targeted therapies is likely required to further decrease disease progression and to promote resolution of chronic lung disease.

PMID: 31778676 [PubMed - as supplied by publisher]

[Adherence of adolescents with cystic fibrosis to enzyme replacement therapy: associated factors].

Cien Saude Colet. 2019 Dec;24(12):4717-4726

Authors: Ferreira DP, Chaves CRMM, Costa ACCD

Abstract
This article sets out to evaluate the prevalence and factors associated with adherence to enzyme replacement therapy among adolescents with cystic fibrosis. It is a cross-sectional, descriptive and observational study. Sociodemographic and clinical data were collected. The instruments used to assess adherence were: the Morisky-Green questionnaire and medication dispensation at the pharmacy, and interviews with structured questionnaires for the associated factors. Forty-four adolescents were interviewed. According to the method of the pharmacy medication dispensation analysis and the Morisky-Green questionnaire, the adherence of 45.5% and 11.4% was found, respectively. The higher adherence was observed in those with early diagnosis and the lowest in older adolescents and girls. The factors with the highest prevalence of non-adherence were: not taking enzymes when eating out of the home; only taking enzymes with major meals; normal lung function; with severe and very severe obstruction. The prevalence of adhesion to enzymes was low. Information related to the disease and treatment should be improved, especially among older adolescents and with impairment of lung function, with the creation of strategies and longitudinal studies to identify factors that interfere with adherence.

PMID: 31778521 [PubMed - in process]

Lung ultrasound assessment of response to antibiotic therapy in cystic fibrosis exacerbations: a study of two cases.

J Bras Pneumol. 2019 Nov 25;45(6):e20190128

Authors: Peixoto AO, Marson FAL, Souza TH, Fraga AMA, Ribeiro JD

PMID: 31778425 [PubMed - in process]

Novel intermicrobial molecular interaction: Pseudomonas aeruginosa Quinolone Signal (PQS) modulates Aspergillus fumigatus response to iron.

Microbiology. 2019 Nov 28;:

Authors: Nazik H, Sass G, Ansari SR, Ertekin R, Haas H, Déziel E, Stevens DA

Abstract
Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af), the commonest bacterium and fungus in compromised host airways, compete for iron (Fe). The Pseudomonas quinolone signal (PQS), a Pa quorum sensing molecule, also chelates Fe, and delivers Fe to the Pa cell membrane using Pa siderophores. In models of Af biofilm formation or preformed biofilms, PQS inhibited Af in a low Fe environment. AfΔsidA (mutant unable to produce siderophores) biofilm was more sensitive to PQS inhibition than wild-type (WT), as was planktonic AfΔsidA growth. PQS decreased WT Af growth on agar. All these inhibitory actions were reversed by Fe. The Pa siderophore pyoverdin, or Af siderophore inhibitor celastrol, act cooperatively with PQS in Af inhibition. These findings all indicate PQS inhibition is owing to Fe chelation. Remarkably, in high Fe environments, PQS enhanced Af biofilm at 1/100 to 1/2000 Fe concentration required for Fe alone to enhance. Planktonic Af growth, and on agar, Af conidiation, were also enhanced by PQS+Fe compared to Fe alone. In contrast, neither AfΔsidA biofilm, nor planktonic AfΔsidA, were enhanced by PQS-Fe compared to Fe. When Af siderophore ferricrocin (FC),+PQS, were added to AfΔsidA, Af was then boosted more than by FC alone. Moreover, FC+PQS+Fe boosted AfΔsidA more than Fe, FC, FC+Fe, PQS+FC or PQS+Fe. Thus PQS-Fe maximal stimulation requires Af siderophores. PQS inhibits Af via chelation under low Fe conditions. In a high Fe environment, PQS paradoxically stimulates Af efficiently, and this involves Af siderophores. PQS production by Pa could stimulate Af in cystic fibrosis airways, where Fe homeostasis is altered and Fe levels increase, supporting fungal growth.

PMID: 31778108 [PubMed - as supplied by publisher]

Recapitulation of polymicrobial communities associated with cystic fibrosis airway infections: a perspective.

Future Microbiol. 2019 Nov 28;:

Authors: O'Brien TJ, Welch M

Abstract
The airways of persons with cystic fibrosis are prone to infection by a diverse and dynamic polymicrobial consortium. Currently, no models exist that permit recapitulation of this consortium within the laboratory. Such microbial ecosystems likely have a network of interspecies interactions, serving to modulate metabolic pathways and impact upon disease severity. The contribution of less abundant/fastidious microbial species on this cross-talk has often been neglected due to lack of experimental tractability. Here, we critically assess the existing models for studying polymicrobial infections. Particular attention is paid to 3Rs-compliant in vitro and in silico infection models, offering significant advantages over mammalian infection models. We outline why these models will likely become the 'go to' approaches when recapitulating polymicrobial cystic fibrosis infection.

PMID: 31778075 [PubMed - as supplied by publisher]

Cystic fibrosis: a call for papers for ECFS 2020.

Lancet Respir Med. 2019 Dec;7(12):1006

Authors: Grainger E

PMID: 31777391 [PubMed - in process]

Treating genes and patients.

Gene Ther. 2019 Nov 27;:

Authors: Wilson J

PMID: 31776472 [PubMed - as supplied by publisher]

Nanomolar-potency 'co-potentiator' therapy for cystic fibrosis caused by a defined subset of minimal function CFTR mutants.

Sci Rep. 2019 Nov 27;9(1):17640

Authors: Phuan PW, Tan JA, Rivera AA, Zlock L, Nielson DW, Finkbeiner WE, Haggie PM, Verkman AS

Abstract
Available CFTR modulators provide no therapeutic benefit for cystic fibrosis (CF) caused by many loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, including N1303K. We previously introduced the concept of 'co-potentiators' (combination-potentiators) to rescue CFTR function in some minimal function CFTR mutants. Herein, a screen of ~120,000 drug-like synthetic small molecules identified active co-potentiators of pyrazoloquinoline, piperidine-pyridoindole, tetrahydroquinoline and phenylazepine classes, with EC50 down to ~300 nM following initial structure-activity studies. Increased CFTR chloride conductance by up to 8-fold was observed when a co-potentiator (termed 'Class II potentiator') was used with a classical potentiator ('Class I potentiator') such as VX-770 or GLPG1837. To investigate the range of CFTR mutations benefitted by co-potentiators, 14 CF-associated CFTR mutations were studied in transfected cell models. Co-potentiator efficacy was found for CFTR missense, deletion and nonsense mutations in nucleotide binding domain-2 (NBD2), including W1282X, N1303K, c.3700A > G and Q1313X (with corrector for some mutations). In contrast, CFTR mutations G85E, R334W, R347P, V520F, R560T, A561E, M1101K and R1162X showed no co-potentiator activity, even with corrector. Co-potentiator efficacy was confirmed in primary human bronchial epithelial cell cultures generated from a N1303K homozygous CF subject. The Class II potentiators identified here may have clinical benefit for CF caused by mutations in the NBD2 domain of CFTR.

PMID: 31776420 [PubMed - in process]

WNT/RYK signaling restricts goblet cell differentiation during lung development and repair.

Proc Natl Acad Sci U S A. 2019 Nov 27;:

Authors: Kim HT, Yin W, Nakamichi Y, Panza P, Grohmann B, Buettner C, Guenther S, Ruppert C, Kobayashi Y, Guenther A, Stainier DYR

Abstract
Goblet cell metaplasia and mucus hypersecretion are observed in many pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. However, the regulation of goblet cell differentiation remains unclear. Here, we identify a regulator of this process in an N-ethyl-N-nitrosourea (ENU) screen for modulators of postnatal lung development; Ryk mutant mice exhibit lung inflammation, goblet cell hyperplasia, and mucus hypersecretion. RYK functions as a WNT coreceptor, and, in the developing lung, we observed high RYK expression in airway epithelial cells and moderate expression in mesenchymal cells as well as in alveolar epithelial cells. From transcriptomic analyses and follow-up studies, we found decreased WNT/β-catenin signaling activity in the mutant lung epithelium. Epithelial-specific Ryk deletion causes goblet cell hyperplasia and mucus hypersecretion but not inflammation, while club cell-specific Ryk deletion in adult stages leads to goblet cell hyperplasia and mucus hypersecretion during regeneration. We also found that the airway epithelium of COPD patients often displays goblet cell metaplastic foci, as well as reduced RYK expression. Altogether, our findings reveal that RYK plays important roles in maintaining the balance between airway epithelial cell populations during development and repair, and that defects in RYK expression or function may contribute to the pathogenesis of human lung diseases.

PMID: 31776260 [PubMed - as supplied by publisher]

International perspectives on the implementation of reproductive carrier screening.

Prenat Diagn. 2019 Nov 27;:

Authors: Delatycki MB, Alkuraya F, Archibald A, Castellani C, Cornel M, Grody WW, Henneman L, Ioannides A, Kirk E, Laing N, Lucassen A, Massie J, Schuurmans J, Thong MK, van Langen I, Zlotogora J

Abstract
Reproductive carrier screening started in some countries in the 1970s for hemoglobinopathies and Tay-Sachs disease. Cystic fibrosis carrier screening became possible in the late 1980s and with technical advances, screening of an ever increasing number of genes has become possible. The goal of carrier screening is to inform people about their risk of having children with autosomal recessive and X-linked recessive disorders, to allow for informed decision making about reproductive options. The consequence may be a decrease in the birth prevalence of these conditions, which has occurred in several countries for some conditions. Different programs target different groups (high school, premarital, couples before conception, couples attending fertility clinics, pregnant women) as does the governance structure (public health initiative, user pays). Ancestry based offers of screening are being replaced by expanded carrier screening panels with multiple genes that is independent of ancestry. This review describes screening in Australia, Cyprus, Israel, Italy, Malaysia, Netherlands, Saudi Arabia, United Kingdom and United States of America. It provides an insight into the enormous variability in how reproductive carrier screening is offered across the globe. This largely relates to geographical variation in carrier frequencies of genetic conditions and local healthcare, financial, cultural and religious factors.

PMID: 31774570 [PubMed - as supplied by publisher]

Obstructive lung diseases and risk of rheumatoid arthritis.

Expert Rev Clin Immunol. 2019 Nov 27;:

Authors: Friedlander HM, Ford JA, Zaccardelli A, Terrio AV, Cho MH, Sparks JA

Abstract
Introduction: Smoking is an established risk factor for both lung diseases and rheumatoid arthritis (RA). Chronic mucosal airway inflammation may result in immune tolerance loss, neoantigen formation, and production of RA-related autoantibodies that increase the subsequent risk of RA. In this review, we aimed to summarize the current evidence supporting the role of obstructive lung diseases and subsequent risk of RA.Areas covered: We identified scientific articles discussing the biologic mechanisms linking mucosal airway inflammation and RA risk. We also identified studies investigating asthma, chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, chronic tuberculous and nontuberculous mycobacterial infections, and interstitial lung disease with subsequent risk for RA.Expert opinion: The current evidence supports the hypothesis that mucosal airway inflammation may increase the risk of developing RA. However, most studies investigating this relationship have been retrospective and may not have adequately addressed the role of smoking. Larger prospective studies may provide stronger evidence for obstructive lung disease and RA risk. Determining the role of obstructive lung disease in RA pathogenesis may provide opportunity for RA prevention and screening strategies, while identifying novel biologic mechanisms that could offer targets to improve treatment and outcomes.

PMID: 31774329 [PubMed - as supplied by publisher]

Positive expiratory pressure physiotherapy for airway clearance in people with cystic fibrosis.

Cochrane Database Syst Rev. 2019 Nov 27;2019(11):

Authors: McIlwaine M, Button B, Nevitt SJ

Abstract
BACKGROUND: Chest physiotherapy is widely prescribed to assist the clearance of airway secretions in people with cystic fibrosis (CF). Positive expiratory pressure (PEP) devices provide back pressure to the airways during expiration. This may improve clearance by building up gas behind mucus via collateral ventilation and by temporarily increasing functional residual capacity. The developers of the PEP technique recommend using PEP with a mask in order to avoid air leaks via the upper airways and mouth. In addition, increasing forced residual capacity (FRC) has not been demonstrated using mouthpiece PEP. Given the widespread use of PEP devices, there is a need to determine the evidence for their effect. This is an update of a previously published review.
OBJECTIVES: To determine the effectiveness and acceptability of PEP devices compared to other forms of physiotherapy as a means of improving mucus clearance and other outcomes in people with CF.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. The electronic database CINAHL was also searched from 1982 to 2017. Most recent search of the Group's CF Trials Register: 20 February 2019.
SELECTION CRITERIA: Randomised controlled studies in which PEP was compared with any other form of physiotherapy in people with CF. This included, postural drainage and percussion (PDPV), active cycle of breathing techniques (ACBT), oscillating PEP devices, thoracic oscillating devices, bilevel positive airway pressure (BiPaP) and exercise.
DATA COLLECTION AND ANALYSIS: Three authors independently applied the inclusion and exclusion criteria to publications, assessed the risk of bias of the included studies and assessed the quality of the evidence using the GRADE recommendations.
MAIN RESULTS: A total of 28 studies (involving 788 children and adults) were included in the review; 18 studies involving 296 participants were cross-over in design. Data were not published in sufficient detail in most of these studies to perform any meta-analysis. In 22 of the 28 studies the PEP technique was performed using a mask, in three of the studies a mouthpiece was used with nose clips and in three studies it was unclear whether a mask or mouthpiece was used. These studies compared PEP to ACBT, autogenic drainage (AD), oral oscillating PEP devices, high-frequency chest wall oscillation (HFCWO) and BiPaP and exercise. Forced expiratory volume in one second was the review's primary outcome and the most frequently reported outcome in the studies (24 studies, 716 participants). Single interventions or series of treatments that continued for up to three months demonstrated little or no difference in effect between PEP and other methods of airway clearance on this outcome (low- to moderate-quality evidence). However, long-term studies had equivocal or conflicting results regarding the effect on this outcome (low- to moderate-quality evidence). A second primary outcome was the number of respiratory exacerbations. There was a lower exacerbation rate in participants using PEP compared to other techniques when used with a mask for at least one year (five studies, 232 participants; moderate- to high-quality evidence). In one of the included studies which used PEP with a mouthpiece, it was reported (personal communication) that there was no difference in the number of respiratory exacerbations (66 participants, low-quality evidence). Participant preference was reported in 10 studies; and in all studies with an intervention period of at least one month, this was in favour of PEP. The results for the remaining outcome measures (including our third primary outcome of mucus clearance) were not examined or reported in sufficient detail to provide any high-quality evidence; only very low- to moderate-quality evidence was available for other outcomes. There was limited evidence reported on adverse events; these were measured in five studies, two of which found no events. In a study where infants performing either PEP or PDPV experienced some gastro-oesophageal reflux , this was more severe in the PDPV group (26 infants, low-quality evidence). In PEP versus oscillating PEP, adverse events were only reported in the flutter group (five participants complained of dizziness, which improved after further instructions on device use was provided) (22 participants, low-quality evidence). In PEP versus HFCWO, from one long-term high-quality study (107 participants) there was little or no difference in terms of number of adverse events; however, those in the PEP group had fewer adverse events related to the lower airways when compared to HFCWO (high-certainty evidence). Many studies had a risk of bias as they did not report how the randomisation sequence was either generated or concealed. Most studies reported the number of dropouts and also reported on all planned outcome measures.
AUTHORS' CONCLUSIONS: The evidence provided by this review is of variable quality, but suggests that all techniques and devices described may have a place in the clinical treatment of people with CF. Following meta-analyses of the effects of PEP versus other airway clearance techniques on lung function and patient preference, this Cochrane Review demonstrated that there was high-quality evidence that showed a significant reduction in pulmonary exacerbations when PEP using a mask was compared with HFCWO. It is important to note that airway clearance techniques should be individualised throughout life according to developmental stages, patient preferences, pulmonary symptoms and lung function. This also applies as conditions vary between baseline function and pulmonary exacerbations.

PMID: 31774149 [PubMed - in process]

Characterization of gallium resistance induced in a Pseudomonas aeruginosa cystic fibrosis isolate.

Arch Microbiol. 2019 Nov 26;:

Authors: Tovar-García A, Angarita-Zapata V, Cazares A, Jasso-Chávez R, Belmont-Díaz J, Sanchez-Torres V, López-Jacome LE, Coria-Jiménez R, Maeda T, García-Contreras R

Abstract
The repurposing of gallium nitrate as an antibacterial, a drug used previously for the treatment of hypercalcemia, is a plausible alternative to combat infections by Pseudomonas aeruginosa, since it has antipseudomonal properties in vitro and in vivo in animal models and in human lung infections. Furthermore, gallium nitrate tolerance in clinical isolates is very rare. Nevertheless, studies on the reference strains PA14 and PAO1 show that resistance against gallium nitrate is achieved by decreasing gallium intracellular levels by increasing the production of pyocyanin. In this work, we induced resistance in a cystic fibrosis P. aeruginosa isolate and explored its resistance mechanisms. This isolated strain, INP-58M, was not a pyocyanin producer, and its pyoverdine levels remained unchanged upon gallium addition. However, it showed higher activities of NADPH-producing enzymes and the antioxidant enzyme SOD when gallium was added, which suggests a better antioxidant response. Remarkably, gallium intracellular levels in the resistant isolate were higher than those of the parental strain at 20 h but lower after 24 h of culture, suggesting that this strain is capable of gallium efflux.

PMID: 31773196 [PubMed - as supplied by publisher]

High Nuclease Activity of Long Persisting Staphylococcus aureus Isolates Within the Airways of Cystic Fibrosis Patients Protects Against NET-Mediated Killing.

Front Immunol. 2019;10:2552

Authors: Herzog S, Dach F, de Buhr N, Niemann S, Schlagowski J, Chaves-Moreno D, Neumann C, Goretzko J, Schwierzeck V, Mellmann A, Dübbers A, Küster P, Schültingkemper H, Rescher U, Pieper DH, von Köckritz-Blickwede M, Kahl BC

Abstract
Staphylococcus aureus is one of the first and most prevalent pathogens cultured from the airways of cystic fibrosis (CF) patients, which can persist there for extended periods. Airway infections in CF patients are characterized by a strong inflammatory response of highly recruited neutrophils. One killing mechanism of neutrophils is the formation of neutrophil extracellular traps (NETs), which capture and eradicate bacteria by extracellular fibers of neutrophil chromatin decorated with antimicrobial granule proteins. S. aureus secretes nuclease, which can degrade NETs. We hypothesized, that S. aureus adapts to the airways of CF patients during persistent infection by escaping from NET-mediated killing via an increase of nuclease activity. Sputum samples of CF patients with chronic S. aureus infection were visualized by confocal microscopy after immuno-fluorescence staining for NET-specific markers, S. aureus bacteria and overall DNA structures. Nuclease activity was analyzed in sequential isogenic long persisting S. aureus isolates, as confirmed by whole genome sequencing, from an individual CF patient using a FRET-based nuclease activity assay. Additionally, some of these isolates were selected and analyzed by qRT-PCR to determine the expression of nuc1 and regulators of interest. NET-killing assays were performed with clinical S. aureus isolates to evaluate killing and bacterial survival depending on nuclease activity. To confirm the role of nuclease during NET-mediated killing, a clinical isolate with low nuclease activity was transformed with a nuclease expression vector (pCM28nuc). Furthermore, two sputa from an individual CF patient were subjected to RNA-sequence analysis to evaluate the activity of nuclease in vivo. In sputa, S. aureus was associated to extracellular DNA structures. Nuclease activity in clinical S. aureus isolates increased in a time-and phenotype-dependent manner. In the clinical isolates, the expression of nuc1 was inversely correlated to the activity of agr and was independent of saeS. NET-mediated killing was significantly higher in S. aureus isolates with low compared to isolates with high nuclease activity. Importantly, transformation of the clinical isolate with low nuclease activity with pCM28nuc conferred protection against NET-mediated killing confirming the beneficial role of nuclease for protection against NETs. Also, nuclease expression in in vivo sputa was high, which underlines the important role of nuclease within the highly inflamed CF airways. In conclusion, our data show that S. aureus adapts to the neutrophil-rich environment of CF airways with increasing nuclease expression most likely to avoid NET-killing during long-term persistence.

PMID: 31772562 [PubMed - in process]

Cystic Fibrosis Lung Disease: An Overview.

Respir Care. 2019 Nov 26;:

Authors: Turcios NL

Abstract
Although better insights into the natural course of cystic fibrosis (CF) have led to treatment approaches that have improved pulmonary health and increased the life expectancy of individuals with this disorder, lung disease remains the main cause of morbidity and mortality in patients with CF. Evidence suggests that airway epithelial defects in ions-water transport lead to dehydrated mucus, impaired mucus clearance, and mucus adhesion to airway surfaces. An increase in mucin secretion is also suggested by the formation of endobronchial mucus plaques and plugs, which become the main sites of air flow obstruction, infection, and inflammation conducing to early small airways disease followed by the development of bronchiectasis. The lung involvement is usually progressive with intermittent exacerbations. Aggressive management and advances in treatment delay, but, do not prevent progression of lung disease. Respiratory failure ensues and is the major cause of death. The lung parenchyma is virtually untouched for much of the course of the disease. This review focuses on the lung involvement in cystic fibrosis and summarizes new developments on the diagnostic approach of CF and pathogenesis of related lung disease. Current therapeutic modalities, novel therapies targeting the basic genetic defect, and lung transplantation are also reviewed.

PMID: 31772069 [PubMed - as supplied by publisher]

Impact of newborn screening on outcomes and social inequalities in cystic fibrosis: a UK CF registry-based study.

Thorax. 2019 Nov 26;:

Authors: Schlüter DK, Southern KW, Dryden C, Diggle P, Taylor-Robinson D

Abstract
BACKGROUND: Newborn bloodspot screening (NBS) for cystic fibrosis (CF) was introduced across the UK in 2007 but the impact on clinical outcomes and health inequalities for children with CF is unclear.
METHODS: We undertook longitudinal analyses of UK CF registry data on over 3000 children with CF born between 2000 and 2015. Clinical outcomes were the trajectories of percent predicted forced expiratory volume in one second (%FEV1) from age 5, weight for age and body mass index (BMI) SD-scores from age one, and time to chronic Pseudomonas aeruginosa (cPA) infection. Using mixed effects and time-to-event models we assessed the association of NBS with outcomes and potential interactions with childhood socioeconomic conditions, while adjusting for confounders.
RESULTS: NBS was associated with higher average lung function trajectory (+1.56 FEV1 percentage points 95% CI 0.1 to 3.02, n=2216), delayed onset of cPA, and higher average weight trajectory intercept at age one (+0.16 SD; 95% CI 0.07 to 0.26, n=3267) but negative rate of weight change thereafter (-0.02 SD per year; 95% CI -0.03 to -0.00). We found no significant association of NBS with BMI or rate of change of lung function. There was no clear evidence of an impact of NBS on health inequalities early in life.
CONCLUSIONS: Children diagnosed with CF by NBS in the UK have better lung function and increased early weight but NBS does not appear to have narrowed early health inequalities.

PMID: 31771956 [PubMed - as supplied by publisher]

Positive clinical outcomes following ivacaftor treatment in a cystic fibrosis patient with the genotype 3272-26A > G/Q493X.

J Cyst Fibros. 2019 Nov 23;:

Authors: Pallin M, Daley CP

PMID: 31771899 [PubMed - as supplied by publisher]

Using photo-elicitation to explore perceptions of physical activity among young people with cystic fibrosis.

BMC Pulm Med. 2019 Nov 26;19(1):220

Authors: Denford S, Hill DM, Mackintosh KA, McNarry MA, Barker AR, Williams CA, Youth Activity Unlimited – A Strategic Research Centre of the UK Cystic Fibrosis Trust

Abstract
BACKGROUND: Physical activity is recommended in the management of cystic fibrosis (CF). The aim of this study was to explore motives, barriers and enablers to physical activity among this population.
METHODS: Twelve participants (12-18 years) were recruited via convenience sampling. Photo-elicitation alongside semi-structured interviews were used to explore participants' views and experiences of physical activity.
RESULTS: Our findings revealed motives for physical activity including health, enjoyment and autonomy. Those with families who valued physical activity tended to have positive attitudes towards physical activity, and valued and integrated it into their lives. Moreover, they were likely to be intrinsically motivated to be active. Several factors enable and act as barriers to physical activity. Whilst CF influenced physical activity, the majority of enablers and barriers raised where congruent with the general populations.
CONCLUSION: This study provides support that healthcare providers should encourage both young people with CF and their families to be active, and subsequently informs the development of clinical interventions to support physical activity among young people with CF and their families.

PMID: 31771568 [PubMed - in process]

Selective Sampling of the Lower Airway in Children with CF: What Are We Missing?

Am J Respir Crit Care Med. 2019 Nov 26;:

Authors: Turnbull A, Hughes D, Davies J

PMID: 31770011 [PubMed - as supplied by publisher]