ERJ Open Res. 2021 Sep 20;7(3):00120-2021. doi: 10.1183/23120541.00120-2021. eCollection 2021 Jul.

ABSTRACT

BACKGROUND: Quality of life has improved dramatically over the past two decades in people with cystic fibrosis (CF). Quantification has been enabled by patient-reported outcome measures (PROMs); however, many are lengthy and can be challenging to use in routine clinical practice. We propose a short-form PROM that correlates well with established quality-of-life measures.

METHODS: We evaluated the utility of a 10-item score (AWESCORE) by measuring reliability, validity and responsiveness in adults with CF. The questions were developed by thematic analysis of survey questions to patients in a single adult CF centre. Each question was scored using a numerical rating scale 0 to 10. Total scores ranged from 0 to 100. Test-retest reliability was assessed over 24 h. To determine validity, comparisons were sought between stable subjects and those in pulmonary exacerbation, and between AWESCORE and Cystic Fibrosis Questionnaire - Revised (CFQ-R). Responsiveness to pulmonary exacerbation in individual subjects was evaluated.

RESULTS: Five domains, each with two questions, were identified for respiratory, physical, nutritional, psychological and general health. A total of 246 consecutive adults attending the outpatient clinic completed the AWESCORE. Scores were higher during clinical stability compared to pulmonary exacerbation (mean± sd): 73±11 versus 48±11 (p<0.001). Each domain scored worse during an acute exacerbation (p<0.001). No differences in reliability were observed in scores on retesting using Bland-Altman comparison. The CFQ-R scores (mean±sd: 813±125) and AWESCORE (81±13) were moderately correlated (Pearson's r=0.649; p=0.002).

CONCLUSIONS: The AWESCORE is valid, reliable and responsive to altered health status in CF.

PMID:34549047 | PMC:PMC8450462 | DOI:10.1183/23120541.00120-2021

Int J Chron Obstruct Pulmon Dis. 2021 Sep 14;16:2585-2590. doi: 10.2147/COPD.S319972. eCollection 2021.

ABSTRACT

PURPOSE: Smoking-induced bronchiolitis with progressive small airway dysfunction (SAD) is a leading cause of chronic obstructive pulmonary disease. We investigated the value of using the impulse oscillometry system (IOS) to detect SAD in asymptomatic smokers with preserved spirometry.

PATIENTS AND METHODS: We included 75 asymptomatic smokers (37 females, mean age 47±12 years, 26±17 pack/year) with preserved spirometry [forced expiratory volume at 1st second (FEV1)/forced vital capacity (FVC) ≥0.70 and normal FVC] and 34 never-smokers (19 females, mean age 42±15 years).

RESULTS: In smokers, pack/years were significantly related to spirometry and IOS parameters (p < 0.05). The values of the fall in resistance from 5 Hz to 20 Hz (R5 - R20) were significantly and inversely related to the values of the ratio of forced expiratory volume in 3 and in 6 seconds (FEV3/FEV6) (p < 0.05). In addition, the percentage of heavy smokers (≥30 pack/year) with R5 - R20 >0.07 kPa·s·L-1, considered as IOS index of SAD, but not with FEV3/FEV6 less than a lower limit of normal, a spirometry index of SAD, was significantly higher than that of mild smokers (<30 pack/year) and never-smokers (p < 0.05).

CONCLUSION: This study demonstrates that IOS has the potential to detect SAD in asymptomatic heavy smokers with preserved spirometry and with FEV3/FEV6 values in the normal range. We confirm that IOS provides parameters which can complement traditional measurements of pulmonary function.

PMID:34548789 | PMC:PMC8449545 | DOI:10.2147/COPD.S319972

J Cyst Fibros. 2021 Sep 18:S1569-1993(21)01372-2. doi: 10.1016/j.jcf.2021.08.031. Online ahead of print.

ABSTRACT

BACKGROUND: With the continued advancement of CFTR modulator therapies there is likely to be a burgeoning population of adult cystic fibrosis (CF) patients unable to expectorate sputum. Consequently, the detection and surveillance of pulmonary colonisation, previously reliant on sputum culture, needs re-examining. We hypothesised that cough swabs analysed with culture-independent analysis of the 16S gene could serve as a surrogate for colonisation of the lower airways.

METHODS: Cough swabs and sputum samples were prospectively collected from consecutive adults and children with CF across two sites at regular outpatient appointments. Conventional culture analysis and next generation sequencing were used to compare paired same day samples.

RESULTS: Twenty-two adults and 8 paediatric patients provided 75 paired cough swabs and sputum samples. Alpha diversity measures showed increased bacterial richness in sputum, while evenness and Simpson's diveristy index were higher in cough swabs. Within each sampling technique, microbial composition showed greater similarity when considering intra-patient variation. Poor concordance was observed between culture independent cough swabs and culture dependent/independent sputum analysis for specific pathogens, with cough swabs unable to accurately identify commonly associated CF pathogens (AUROCC range: 0.51 to 0.64).

CONCLUSION: Culture independent analysis of cough swabs provides an inaccurate diagnosis of lower respiratory tract colonisation and should not be used as a diagnostic test in patients with CF.

PMID:34548223 | DOI:10.1016/j.jcf.2021.08.031

J Heart Lung Transplant. 2021 Aug 25:S1053-2498(21)02459-1. doi: 10.1016/j.healun.2021.08.005. Online ahead of print.

ABSTRACT

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly utilized as a bridge to lung transplantation, but ECMO status is not explicitly accounted for in the Lung Allocation Score (LAS). We hypothesized that among waitlist patients on ECMO, patients with pulmonary arterial hypertension (PAH) would have lower transplantation rates.

METHODS: Using United Network for Organ Sharing data, we conducted a retrospective cohort study of patients who were ≥12 years old, active on the lung transplant waitlist, and required ECMO support from June 1, 2015 through June 12, 2020. Multivariable competing risk analysis was used to examine waitlist outcomes.

RESULTS: 1064 waitlist subjects required ECMO support; 40 (3.8%) had obstructive lung disease (OLD), 97 (9.1%) had PAH,138 (13.0%) had cystic fibrosis (CF), and 789 (74.1%) had interstitial lung disease (ILD). Ultimately, 671 (63.1%) underwent transplant, while 334 (31.4%) died or were delisted. The transplant rate per person-years on the waitlist on ECMO was 15.41 for OLD, 6.05 for PAH, 15.66 for CF, and 15.62 for ILD. Compared to PAH patients, OLD, CF, and ILD patients were 78%, 69%, and 62% more likely to undergo transplant throughout the study period, respectively (adjusted SHRs 1.78 p = 0.007, 1.69 p = 0.002, and 1.62 p = 0.001). The median LAS at waitlist removal for transplantation, death, or delisting were 75.1 for OLD, 79.6 for PAH, 91.0 for CF, and 88.3 for ILD (p < 0.001).

CONCLUSIONS: Among patients bridging to transplant on ECMO, patients with PAH had a lower transplantation rate than patients with OLD, CF, and ILD.

PMID:34548196 | DOI:10.1016/j.healun.2021.08.005

Transplant Proc. 2021 Sep 18:S0041-1345(21)00553-4. doi: 10.1016/j.transproceed.2021.08.022. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) and tuberous sclerosis complex (TSC) are 2 rare genetic diseases that often affect the lungs. Pulmonary compromise in TSC or CF can be severe enough to require lung transplantation. In rare instances patients with CF undergo pneumonectomy to control recurrent lung infections and lung necrosis affecting one lung more than the other. Lung transplantation in these patients is exceedingly rare because preexistent pneumonectomy increases the risk of lung transplant-associated morbidity and mortality.

CASE PRESENTATION: We present the case of a young woman with co-occurrence of TSC and CF, who underwent left-sided pneumonectomy and, approximately 2 years later, right-sided single lung transplant. The posttransplant clinical course was complicated by phrenic nerve injury, ventilator dependency, Aspergillus endocarditis with embolic shower, and death. Pretransplant pneumonectomy, Aspergillus colonization, and posttransplant phrenic nerve injury contributed to the complex postoperative course, ventilatory dependence, and poor outcome.

CONCLUSION: This cautionary case should alert physicians on the challenges associated with single lung transplant in patients with preexistent pneumonectomy.

PMID:34548180 | DOI:10.1016/j.transproceed.2021.08.022

BMC Pulm Med. 2021 Sep 21;21(1):298. doi: 10.1186/s12890-021-01669-2.

ABSTRACT

BACKGROUND: Physiotherapy is a cornerstone of cystic fibrosis (CF) management, yet the Australian CF Data Registry (ACFDR) currently does not record physiotherapy-related data. This study aimed to gather opinions from lead Australian CF physiotherapists regarding the importance and feasibility of collecting physiotherapy-related data on the ACFDR.

METHODS: A three-round online Delphi survey was conducted to gather expert stakeholder opinion and consensus agreement. Lead physiotherapists from all 23 Australian CF centres were invited to participate. Round one explored the potential benefits, barriers and importance of recording three physiotherapy-related domains on the ACFDR: airway clearance, physical activity and fitness. Subsequent rounds were developed based on the findings from the previous round and sought consensus (80% agreement) for the inclusion of physiotherapy-related data on the ACFDR and for the most appropriate methods of collecting such data.

RESULTS: The response rate was > 80% for all rounds. Participants agreed that collection of airway clearance, physical activity and fitness data on the ACFDR was important and feasible. Findings suggested that airway clearance and physical activity should be collected using self-reported questionnaires, while fitness should be measured using a field-based test.

CONCLUSIONS: Australian lead CF physiotherapists believe that collection of airway clearance, physical activity and fitness on the ACFDR is important and feasible. Future work is needed to pilot the data collection procedure to examine its feasibility in real-world clinical settings. This study demonstrates how Delphi methodology can provide a contemporary summary of expert clinicians' opinion that may underpin nation-wide health service improvement.

PMID:34548053 | DOI:10.1186/s12890-021-01669-2

Int J Antimicrob Agents. 2021 Sep 18:106438. doi: 10.1016/j.ijantimicag.2021.106438. Online ahead of print.

ABSTRACT

BACKGROUND: There is growing concern regarding the lack of novel antimicrobial agents and increasing resistance of microorganisms to existing agents. This has stimulated the exploration of novel strategies for infection treatment.

OBJECTIVE: To investigate synergistic interactions between five tetracyclines and tobramycin with an iron chelator (CP762) against two reference strains and nine clinical isolates of Pseudomonas aeruginosa from cystic fibrosis patients.

METHOD: Microdilution assays for minimal inhibitory concentration determination and checkerboard assays were used to assess synergy between antibiotics and CP762. Given the iron binding capacity of tetracyclines, the binding of iron with doxycycline was investigated using Job's plot methodology. The iron bound form of doxycycline was compared with the unbound agent in terms of the synergy observed. Enhancement of doxycycline anti-biofilm activity was also assessed.

RESULTS: Synergistic activity with CP762 was evident for all tetracyclines, except minocycline, against the reference strains but activity against clinical isolates was variable. Synergy was not demonstrated for tobramycin against any of the strains tested. This led to the hypothesis that iron chelation preserves the binding nature of tetracyclines to the bacterial ribosome. Susceptibility to iron bound doxycycline was decreased by two to four-fold and synergistic interactions with the iron chelator were consistently found to be more intense with iron-bound doxycycline than with the antibiotic alone. The doxycycline - iron chelator combination also significantly reduced cell viability in established biofilms.

CONCLUSION: The data in this study provides evidence that iron chelation enhances the anti-pseudomonal activity of tetracyclines, and more specifically, of doxycycline.

PMID:34547423 | DOI:10.1016/j.ijantimicag.2021.106438

Biophys J. 2021 Sep 18:S0006-3495(21)00787-6. doi: 10.1016/j.bpj.2021.09.025. Online ahead of print.

ABSTRACT

ATP release by red blood cells (RBCs) under shear stress (SS) plays a pivotal role in endothelial biochemical signaling cascades. The aim of this study is to investigate through numerical simulation how does RBCs spatio-temporal organization depend on flow and geometrical conditions to generate ATP patterns. Numerical simulations were conducted in a straight channel by considering both plasma and explicit presence of RBCs, their shape deformation and cell-cell interaction, as well as ATP release by RBCs. Two ATP release pathways through cell membrane are taken into account, pannexin 1 channel (Px1), sensitive to SS, and cystic fibrosis transmembrane conductance regulator (CFTR) which responds to cell deformation. Several flow and hematocrit conditions are explored. The problem is solved by lattice Boltzmann method. Application of SS to the RBC suspension triggers a nontrivial spatial RBC organization and ATP patterns. ATP localizes preferentially in the vicinity of cell-free layer close to channel wall. Conditions for maximal ATP release per cell are identified, which depend on vessel size and hematocrit Ht. Increasing further Ht beyond optimum enhances the total ATP release but should degrade oxygen transport capacity, a compromise between an efficient ATP release and minimal blood dissipation. Moreover, ATP is boosted in capillaries suggesting a vasomotor activity coordination throughout the resistance network.

PMID:34547277 | DOI:10.1016/j.bpj.2021.09.025

Immunology. 2021 Sep 21. doi: 10.1111/imm.13419. Online ahead of print.

ABSTRACT

Neutrophils are critical components of the body's immune response to infection, being loaded with a potent arsenal of toxic mediators and displaying immense destructive capacity. Given the potential of neutrophils to impart extensive tissue damage, it is perhaps not surprising that when augmented these cells are also implicated in the pathology of inflammatory diseases. Prominent neutrophilic inflammation is a hallmark feature of patients with chronic lung diseases such as chronic obstructive pulmonary disease, severe asthma, bronchiectasis and cystic fibrosis, with their numbers frequently associating with worse prognosis. Accordingly, it is anticipated that neutrophils are central to the pathology of these diseases and represent an attractive therapeutic target. However, in many instances, evidence directly linking neutrophils to the pathology of disease has remained somewhat circumstantial and strategies that have looked to reduce neutrophilic inflammation in the clinic have proved largely disappointing. We have classically viewed neutrophils as somewhat crude, terminally differentiated, insular and homogenous protagonists of pathology. However, it is now clear that this does not do the neutrophil justice, and we now recognize that these cells exhibit heterogeneity, a pronounced awareness of the localized environment and a remarkable capacity to interact with and modulate the behaviour of a multitude of cells, even exhibiting anti-inflammatory, pro-resolving and pro-repair functions. In this review, we discuss evidence for the role of neutrophils in chronic lung disease and how our evolving view of these cells may impact upon our perceived assessment of their contribution to disease pathology and efforts to target them therapeutically.

PMID:34547115 | DOI:10.1111/imm.13419

Virulence. 2021 Dec;12(1):2415-2429. doi: 10.1080/21505594.2021.1959808.

ABSTRACT

Mycobacterium (M.) abscessus infections in Cystic Fibrosis (CF) patients cause a deterioration of lung function. Treatment of these multidrug-resistant pathogens is associated with severe side-effects, while frequently unsuccessful. Insight on M. abscessus genomic evolvement during chronic lung infection would be beneficial for improving treatment strategies. A longitudinal study enrolling 42 CF patients was performed at a CF center in Berlin, Germany, to elaborate phylogeny and genomic diversification of in-patient M. abscessus. Eleven of the 42 CF patients were infected with M. abscessus. Five of these 11 patients were infected with global human-transmissible M. abscessus cluster strains. Phylogenetic analysis of 88 genomes from isolates of the 11 patients excluded occurrence of M. abscessus transmission among members of the study group. Genome sequencing and variant analysis of 30 isolates from 11 serial respiratory samples collected over 4.5 years from a chronically infected patient demonstrated accumulation of gene mutations. In total, 53 genes exhibiting non-synonymous variations were identified. Enrichment analysis emphasized genes involved in synthesis of glycopeptidolipids, genes from the embABC (arabinosyltransferase) operon, betA (glucose-methanol-choline oxidoreductase) and choD (cholesterol oxidase). Genetic diversity evolved in a variety of virulence- and resistance-associated genes. The strategy of M. abscessus populations in chronic lung infection is not clonal expansion of dominant variants, but to sustain simultaneously a wide range of genetic variants facilitating adaptation of the population to changing living conditions in the lung. Genomic diversification during chronic infection requires increased attention when new control strategies against M. abscessus infections are explored.

PMID:34546836 | DOI:10.1080/21505594.2021.1959808

mSystems. 2021 Sep 21:e0073221. doi: 10.1128/mSystems.00732-21. Online ahead of print.

ABSTRACT

Metabolic flexibility of Pseudomonas aeruginosa could lead to new strategies to combat bacterial infection. The present study used gas chromatography-mass spectrometry (GC-MS)-based metabolomics to investigate global metabolism in naturally and artificially evolved strains with cefoperazone-sulbactam (SCF) resistance (AP-RCLIN-EVO and AP-RLAB-EVO, respectively) from the same parent strain (AP-RCLIN). Inactivation of the pyruvate cycle and nitric oxide (NO) biosynthesis was identified as characteristic features of SCF resistance in both evolved strains. Nitrite-dependent NO biosynthesis instead of an arginine-dependent NO pathway is responsible for the reduced NO, which is attributed to lower nitrite and electrons from the oxidation of NADH to NAD+ provided by the pyruvate cycle. Exogenous fumarate, NADH, nitrate, and nitrite promoted the NO level and thereby potentiated SCF-mediated killing. Unexpectedly, fumarate caused the elevation of nitrite, while nitrite/nitrate resulted in the increase of Cyt bc1 complex (providing electrons). These interesting findings indicate that the nitrite-dependent NO biosynthesis and the pyruvate cycle are mutual to promote NO metabolism. In addition, the NO-potentiated sensitivity to SCF was validated by NO donor sodium nitroprusside. These results reveal an endogenous NO-mediated SCF resistance and develop its reversion by metabolites in P. aeruginosa. IMPORTANCE Infections with Pseudomonas aeruginosa have become a real concern among hospital-acquired infections, especially in cystic fibrosis patients and immunocompromised individuals. Control of the pathogen is challenging due to antibiotic resistance. Since bacterial metabolic state impacts sensitivity and resistance to antibiotics, exploring and disclosing bacterial metabolic mechanisms can be used to develop a metabolome-reprogramming approach to elevate bacterial sensitivity to antibiotics. Therefore, GC-MS-based metabolomics is used to explore the similarities and differences of metabolomes between naturally and artificially evolved cefoperazone-sulbactam (SCF)-resistant P. aeruginosa (AP-RCLIN-EVO and AP-RLAB-EVO, respectively) from the same parent strain (AP-RCLIN). It identifies the depressed nitrite-dependent nitric oxide (NO) biosynthesis as the most overlapping characteristic feature between AP-RCLIN-EVO and AP-RLAB-EVO. This is because the pyruvate cycle fluctuates, thereby generating fewer NADH and providing fewer electrons for nitrite-dependent NO biosynthesis than the control. Interestingly, exogenous fumarate, NADH, nitrate, and nitrite as well as NO donor sodium nitroprusside promote NO generation to elevate sensitivity to SCF. These results highlight the way to understand metabolic mechanisms of antibiotic resistance and explore metabolic modulation to combat the bacterial pathogen.

PMID:34546070 | DOI:10.1128/mSystems.00732-21

Stem Cells Transl Med. 2021 Sep 21. doi: 10.1002/sctm.21-0032. Online ahead of print.

ABSTRACT

Chronic lung disease has been attributed to stem cell aging and/or exhaustion. We investigated these mechanisms using mouse and human tracheobronchial tissue-specific stem cells (TSC). In mouse, chromatin labeling and flow cytometry demonstrated that naphthalene (NA) injury activated a subset of TSC. These activated TSC continued to proliferate after the epithelium was repaired and a clone study demonstrated that ~96% of activated TSC underwent terminal differentiation. Despite TSC attrition, epithelial repair after a second NA injury was normal. The second injury accelerated proliferation of previously activated TSC and a nucleotide-label retention study indicated that the second injury recruited TSC that were quiescent during the first injury. These mouse studies indicate that (a) injury causes selective activation of the TSC pool; (b) activated TSC are predisposed to further proliferation; and (c) the activated state leads to terminal differentiation. In human TSC, repeated proliferation also led to terminal differentiation and depleted the TSC pool. A clone study identified long- and short-lived TSC and showed that short-lived TSC clones had significantly shorter telomeres than their long-lived counterparts. The TSC pool was significantly depleted in dyskeratosis congenita donors, who harbor mutations in telomere biology genes. The remaining TSC had short telomeres and short lifespans. Collectively, the mouse and human studies support a model in which epithelial injury increases the biological age of the responding TSC. When applied to chronic lung disease, this model suggests that repeated injury accelerates the biological aging process resulting in abnormal repair and disease initiation.

PMID:34546001 | DOI:10.1002/sctm.21-0032

Nat Microbiol. 2021 Sep 20. doi: 10.1038/s41564-021-00963-3. Online ahead of print.

ABSTRACT

Mycobacterium abscessus, a multidrug-resistant nontuberculous mycobacterium, has emerged as a major pathogen affecting people with cystic fibrosis (CF). Although originally thought to be acquired independently from the environment, most individuals are infected with one of several dominant circulating clones (DCCs), indicating the presence of global transmission networks of M. abscessus. How and when these clones emerged and spread globally is unclear. Here, we use evolutionary analyses of isolates from individuals both with and without CF to reconstruct the population history, spatiotemporal spread and recent transmission networks of the DCCs. We demonstrate synchronous expansion of six unrelated DCCs in the 1960s, a period associated with major changes in CF care and survival. Each of these clones has spread globally as a result of rare intercontinental transmission events. We show that the DCCs, but not environmentally acquired isolates, exhibit a specific smoking-associated mutational signature and that current transmission networks include individuals both with and without CF. We therefore propose that the DCCs initially emerged in non-CF populations but were then amplified and spread through the CF community. While individuals with CF are probably the most permissive host, non-CF individuals continue to play a key role in transmission networks and may facilitate long-distance transmission.

PMID:34545208 | DOI:10.1038/s41564-021-00963-3

mBio. 2021 Sep 21:e0176321. doi: 10.1128/mBio.01763-21. Online ahead of print.

ABSTRACT

A recent workshop titled "Developing Models to Study Polymicrobial Infections," sponsored by the Dartmouth Cystic Fibrosis Center (DartCF), explored the development of new models to study the polymicrobial infections associated with the airways of persons with cystic fibrosis (CF). The workshop gathered 35+ investigators over two virtual sessions. Here, we present the findings of this workshop, summarize some of the challenges involved with developing such models, and suggest three frameworks to tackle this complex problem. The frameworks proposed here, we believe, could be generally useful in developing new model systems for other infectious diseases. Developing and validating new approaches to study the complex polymicrobial communities in the CF airway could open windows to new therapeutics to treat these recalcitrant infections, as well as uncovering organizing principles applicable to chronic polymicrobial infections more generally.

PMID:34544277 | DOI:10.1128/mBio.01763-21

Am J Respir Crit Care Med. 2021 Sep 20. doi: 10.1164/rccm.202108-1939ED. Online ahead of print.

NO ABSTRACT

PMID:34543576 | DOI:10.1164/rccm.202108-1939ED

Ther Adv Respir Dis. 2021 Jan-Dec;15:17534666211046774. doi: 10.1177/17534666211046774.

ABSTRACT

BACKGROUND: Lumacaftor/ivacaftor (LUM/IVA) has shown modest benefits in previous research, but the exact effects in the cystic fibrosis (CF) lung remain unclear. This study aims to offer novel information on the mode of action of the cystic fibrosis transmembrane conductance regulator (CFTR)-modulating drug by assessing lung structure and function using functional respiratory imaging (FRI).

METHODS: CF patients aged ⩾12 years homozygous for F508del were recruited in an open-label study. Before and after 12 weeks of treatment with LUM/IVA, FRI was used to visualize regional information, such as air trapping, lobar volume and airway wall volume. Secondary outcomes included the CF-CT scoring system, spirometry, the Cystic Fibrosis Questionnaire-Revised (CFQ-R) questionnaire, exercise tolerance and nutritional status.

RESULTS: Of the 12 patients enrolled in the study, 11 completed all study visits. Concerning the FRI parameters, hyperinflation of the lung decreased, indicated by a reduction in air trapping and lobar volume at expiration. Also, a decrease in airway wall volume and a redistribution of pulmonary blood volume were noted, which might be related to a decrease in mucus impaction. Airway resistance, airway volume, internal airflow distribution and aerosol deposition pattern did not show significant changes. No significant improvements were found in any of the CF-CT scores or in the spirometric parameters. Other secondary outcomes showed similar results compared with previous research. Correlations at baseline were found between FRI and conventional outcomes, including physical functioning, spirometry and CF-CT scores.

CONCLUSIONS: LUM/IVA decreased lung hyperinflation in combination with a potential decrease in mucus impaction, which can be related to an improved mucociliary transport. These results indicate that several FRI parameters, reflecting regional and distal lung structures, are more sensitive to changes caused by LUM/IVA than conventional respiratory outcomes.

PMID:34541955 | DOI:10.1177/17534666211046774

Ann Otol Rhinol Laryngol. 2021 Sep 18:34894211045270. doi: 10.1177/00034894211045270. Online ahead of print.

ABSTRACT

OBJECTIVES: While adenoidectomy is the first-line surgical management of chronic rhinosinusitis (CRS) in young children, evidence regarding its utility in older children is lacking. This study aimed to assess the efficacy of adenoidectomy in children 7 to 18 years old with regard to symptom control, postoperative medication use, and the need for additional surgery.

METHODS: Single-institution retrospective chart review of patients ages 7 to 18 undergoing adenoidectomy for CRS from 2009 to 2019. Patients with cystic fibrosis and ciliary disorders were excluded. Comorbidities, preoperative and postoperative symptoms (rhinorrhea, congestion, anosmia, and facial pain), medication use (antibiotics, antihistamines, nasal steroids, and irrigations), and Lund-Mackay scores were extracted. McNemar's or Wilcoxon Rank Sum Tests were used to assess rates of symptom control and medication use. Fisher's exact or Chi-square tests were used to assess for factors associated with symptom persistence.

RESULTS: Ninety-seven patients with a mean age of 9 years (range 7-18) were identified. Patients were shown to experience significantly decreased rates of rhinorrhea (64.9% vs 20.6%, <.001), congestion (95.9% vs 26.8%, <.001), facial pain (17.5% vs 3.1%, .001), use of nasal steroids (79.4% vs 36.1%, <.001), antihistamines (47.4% vs 20.6%, <.001), and number of antibiotics (median 1 vs 0, <.001) after adenoidectomy. No patient or disease factors were associated with symptom persistence. Nine patients (9.3%) required additional nasal surgery.

CONCLUSION: In this cohort of older children with CRS with limited follow up, additional surgery is not routinely done following adenoidectomy, the results suggest that adenoidectomy alone may provide adequate symptom control and medication reduction.

PMID:34541924 | DOI:10.1177/00034894211045270

Intern Med J. 2021 Sep;51(9):1526-1529. doi: 10.1111/imj.15483.

ABSTRACT

There are no published data on Australian adult cystic fibrosis (CF) patient outcomes post bronchial arterial embolisation (BAE). We report 20 years of experience of BAE at a major Australian tertiary adult CF centre, where 46 patients underwent 100 BAE during this period. Mortality rate was comparable to previous studies (4% per year) and most who died had repeat BAE requirements. A higher proportion (9 out of 45) of patients were transplanted compared to previous publications. Repeat BAE was common and significantly higher in patients already on tranexamic acid.

PMID:34541776 | DOI:10.1111/imj.15483

Bioact Mater. 2021 Jul 3;8:95-108. doi: 10.1016/j.bioactmat.2021.06.034. eCollection 2022 Feb.

ABSTRACT

Magnesium metal and its alloys are being developed as effective orthopedic implants; however, the mechanisms underlying the actions of magnesium on bones remain unclear. Cystic fibrosis, the most common genetic disease in Caucasians caused by the mutation of CFTR, has shown bone disorder as a key clinical manifestation, which currently lacks effective therapeutic options. Here we report that implantation of magnesium-containing implant stimulates bone formation and improves bone fracture healing in CFTR-mutant mice. Wnt/β-catenin signaling in the bone is enhanced by the magnesium implant, and inhibition of Wnt/β-catenin by iCRT14 blocks the magnesium implant to improve fracture healing in CFTR-mutant mice. We further demonstrate that magnesium ion enters osteocytes, increases intracellular cAMP level and activates ATF4, a key transcription factor known to regulate Wnt/β-catenin signaling. In vivo knockdown of ATF4 abolishes the magnesium implant-activated β-catenin in bones and reverses the improved-fracture healing in CFTR-mutant mice. In addition, oral supplementation of magnesium activates ATF4 and β-catenin as well as enhances bone volume and density in CFTR-mutant mice. Together, these results show that magnesium implantation or supplementation may serve as a potential anabolic therapy for cystic fibrosis-related bone disease. Activation of ATF4-dependent Wnt/β-catenin signaling in osteocytes is identified as a previously undefined mechanism underlying the beneficial effect of magnesium on bone formation.

PMID:34541389 | PMC:PMC8424424 | DOI:10.1016/j.bioactmat.2021.06.034

Cureus. 2021 Aug 16;13(8):e17229. doi: 10.7759/cureus.17229. eCollection 2021 Aug.

ABSTRACT

A 25-year-old male with end-stage cystic fibrosis (CF) with genotype F508del/F508del presented to the clinic complaining of bilateral knee and ankle pain. He had severe lung disease (forced expiratory volume 1 {FEV1} 19% of predicted), chronic colonization with achromobacter, malnutrition, and CF-related diabetes. On physical examination, he was found to have bilateral knee swelling as well as pain on flexion and extension of the wrists and ankles without erythema or warmth. He was empirically started on prednisone and tramadol; however, at a three-month follow-up visit, he remained symptomatic. He was sent for a whole-body bone scan, which was consistent with hypertrophic pulmonary osteoarthropathy (HPOA). He was started on highly effective modulator therapy with elexacaftor/tezacaftor/ivacaftor and symptoms spontaneously resolved without further intervention.

PMID:34540456 | PMC:PMC8442824 | DOI:10.7759/cureus.17229