Cureus. 2021 Aug 25;13(8):e17427. doi: 10.7759/cureus.17427. eCollection 2021 Aug.

ABSTRACT

Cystic fibrosis (CF) is the most common genetic disease in the United States (US) and, with the development of newer therapeutics, there is increased fertility among women with CF. We present a series of pregnant patients taking novel CF transmembrane conductance regulator (CFTR) modulators and summarize pertinent clinical considerations. All women conceived within four months after starting elexacaftor-ivacaftor-tezacaftor. Pulmonary function was stable before and during pregnancy. One patient developed transaminitis necessitating discontinuation of the medication mid-trimester. All patients delivered healthy neonates between 36-38 weeks of gestation with uncomplicated postpartum courses. No birth defects were encountered. Given that newly introduced CFTR modulators may increase fertility among CF patients, contraception counseling, pulmonary function monitoring, liver function monitoring, and multi-disciplinary care are important pillars of management.

PMID:34589336 | PMC:PMC8460487 | DOI:10.7759/cureus.17427

Eur Respir J. 2021 Sep 29:2101293. doi: 10.1183/13993003.01293-2021. Online ahead of print.

ABSTRACT

Chronic airway inflammation is the main driver of pathogenesis in respiratory diseases, such as severe asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and bronchiectasis. While the role of common pathogens in airway inflammation is widely recognized, the influence of other microbiota members is still poorly understood. Here, we show that Rothia mucilaginosa, a common resident of the oral cavity that is also often detectable in the lower airways in chronic disease, has an inhibitory effect on pathogen- and LPS-induced pro-inflammatory responses, both in vitro (3-D cell culture model) and in vivo (mouse model). Furthermore, in a cohort of adults with bronchiectasis, the abundance of Rothia spp. was negatively correlated with pro-inflammatory markers (IL-8, IL-1β) and matrix metalloproteinases (MMP-1, MMP-8 and MMP-9) in sputum. Mechanistic studies revealed that R. mucilaginosa inhibits NF-κB pathway activation by reducing the phosphorylation of IκB-α and consequently the expression of NF-κB target genes. These findings indicate that the presence of R. mucilaginosa in the lower airways potentially mitigates inflammation, which could in turn influence severity and progression of chronic respiratory disorders.

PMID:34588194 | DOI:10.1183/13993003.01293-2021

J Cyst Fibros. 2021 Sep 27:S1569-1993(21)01358-8. doi: 10.1016/j.jcf.2021.08.017. Online ahead of print.

ABSTRACT

BACKGROUND: Acute exacerbations of Cystic Fibrosis (AECF) are associated with significant morbidity. Recommendations are to treat for 2-3 weeks despite limited data. Spirometry is a measure of clinical response yet appears to plateau at 7-10 days. While durations <9 days have been associated with poorer outcomes, a duration of 10 days may be as effective as 14 days, potentially conferring advantages in terms of cost and adverse events. A 2019 Cochrane review by Abbott et al. did not identify any randomised controlled trials (RCT) comparing durations of treatment. Utilising data from non-randomised studies (NRS), we report a systematic review of intravenous antibiotic treatment, exploring changes in FEV1 (Forced Expiratory Volume in 1 second), CRP (C-reactive protein) and peripheral WBC (white blood cell) count in studies with different treatment durations.

STUDY DESIGN AND METHODS: Systematic review of published literature following a search of MEDLINE, Embase, CINAHL and the Cochrane Clinical Trials register. Guidelines from the Preferred Reporting items for Systematic reviews and Meta-Analysis (PRISMA) and reporting Meta-analysis of Observational studies (MOOSE) statement were followed.

RESULTS: No randomised controlled trials were identified that specifically examined duration of treatment during AECF. This study included all relevant RCTs and also NRS, grouping according to study characteristics, such as length of treatment, location, year, and also characteristics of the patient population. 52 studies, comprising 79 subgroups, and 1,597 patients, were identified. Mean change (95%CI) in ppFEV1 was 10.13 (9.21-11.05). There was no significant difference in change in ppFEV1 for studies treating for 10-12 days; 8.85 (7.47-10.23), vs 13-15 days; 10.68 (9.53-11.82). Similar changes in CRP and WBC were seen irrespective of treatment duration.

CONCLUSION: This systematic review provides evidence that shorter durations of treatment may be associated with similar changes in FEV1, CRP and WBC compared with longer durations.

PMID:34588142 | DOI:10.1016/j.jcf.2021.08.017

Ther Adv Respir Dis. 2021 Jan-Dec;15:17534666211042534. doi: 10.1177/17534666211042534.

ABSTRACT

The risks of overusing short-acting β2-agonists (SABA), including an increase in asthma-related deaths, are many and well known. The Global Initiative on Asthma (GINA) 2019 and 2020 updates recommend as-needed inhaled corticosteroid (ICS)/formoterol as the preferred rescue medication in mild asthma as monotherapy and also in moderate to severe asthma when the maintenance and reliever therapy (MART) strategy is used. Using SABA for symptom relief, however, was the standard of treatment for many years, and consequently this practice persists, particularly in patients not taking ICS regularly. Here, we examine the rationale for this shift from a long-standing recommendation for as-needed SABA treatment to the use of as-needed ICS/formoterol and consider clinical evidence on strategies for asthma treatment and patient management.

PMID:34587829 | DOI:10.1177/17534666211042534

J Physiol. 2021 Sep 29. doi: 10.1113/JP281765. Online ahead of print.

ABSTRACT

KEY POINTS: Cystic fibrosis transmembrane conductance regulator (CFTR) is an important ion channel in epithelial cells. Its malfunction has several serious consequences, like developing or aggravating acute pancreatitis (AP). Here, we investigated the localization and expression of CFTR during cerulein-induced AP in mice and determined the effects of CFTR corrector (VX-661) and potentiator (VX-770) on disease severity. CFTR mRNA expression was significantly increased, and mislocalization of CFTR protein was observed in AP compared to the control group. Interestingly, pre-treatment of AP mice with VX-661 + VX-770 significantly reduced the extent of pancreatic tissue damage by 20-30%. In vitro administration of VX-661 + VX-770 significantly increased the fluid secretion of ducts derived from AP animals. Based on our results, the utilization of CFTR correctors and potentiators should be further investigated in AP.

ABSTRACT: Cystic fibrosis transmembrane conductance regulator (CFTR) has essential role in maintaining pancreatic ductal function. Impaired CFTR function can trigger acute pancreatitis (AP) and exacerbate disease severity. We aimed to investigate the localization and expression of CFTR during AP, and determined the effects of CFTR corrector (VX-661) and potentiator (VX-770) on disease severity. AP was induced in FVB/n mice by 6-10 hourly intraperitoneal injections of 50μg/kg cerulein. Some mice were pre-treated with 5-6 daily injections of 2mg/kg VX-661+VX-770. Control animals were administered physiological saline instead of cerulein and DMSO instead of VX compounds. AP severity was determined by measuring laboratory and histological parameters; CFTR and CK19 expressions were measured. Activity of ion transporters was followed by intracellular pH or fluid secretion measurement of isolated pancreatic intra-/interlobular ducts. Cerulein-induced AP severity was greatest between 12-24h. CFTR mRNA expression was significantly increased 24h after AP induction. Immunohistochemistry demonstrated disturbed staining morphology of CFTR and CK19 proteins in AP. Mislocalization of CFTR protein was observed from 6h, while expression increased at 24h compared to control. Ductal HCO3 - transport activity was significantly increased 6h after AP induction. AP mice pre-treatment with VX-661+VX-770 significantly reduced the extent of tissue damage by about 20-30%, but other parameters were unchanged. Interestingly, VX-661+VX-770 in vitro administration significantly increased the fluid secretion of ducts derived from AP animals. This study described the course of the CFTR expression and mislocalization in cerulein-induced AP. Our results suggest that the beneficial effects of CFTR correctors and potentiators should be further investigated in AP. This article is protected by copyright. All rights reserved.

PMID:34587656 | DOI:10.1113/JP281765

PLoS One. 2021 Sep 29;16(9):e0237659. doi: 10.1371/journal.pone.0237659. eCollection 2021.

ABSTRACT

Several antibiotics demonstrate both antibacterial and anti-inflammatory/immunomodulatory activities and are used to treat inflammatory pulmonary disorders. Lefamulin is a pleuromutilin antibiotic approved to treat community-acquired bacterial pneumonia (CABP). This study evaluated lefamulin anti-inflammatory effects in vivo and in vitro in a lipopolysaccharide-induced lung neutrophilia model in which mouse airways were challenged with intranasal lipopolysaccharide. Lefamulin and comparators azithromycin and dexamethasone were administered 30min before lipopolysaccharide challenge; neutrophil infiltration into BALF and inflammatory mediator induction in lung homogenates were measured 4h postchallenge. Single subcutaneous lefamulin doses (10‒140mg/kg) resulted in dose-dependent reductions of BALF neutrophil cell counts, comparable to or more potent than subcutaneous azithromycin (10‒100mg/kg) and oral/intraperitoneal dexamethasone (0.5/1mg/kg). Lipopolysaccharide-induced pro-inflammatory cytokine (TNF-α, IL-6, IL-1β, and GM-CSF), chemokine (CXCL-1, CXCL-2, and CCL-2), and MMP-9 levels were significantly and dose-dependently reduced in mouse lung tissue with lefamulin; effects were comparable to or more potent than with dexamethasone or azithromycin. Pharmacokinetic analyses confirmed exposure-equivalence of 30mg/kg subcutaneous lefamulin in mice to a single clinical lefamulin dose to treat CABP in humans (150mg intravenous/600mg oral). In vitro, neither lefamulin nor azithromycin had any relevant influence on lipopolysaccharide-induced cytokine/chemokine levels in J774.2 mouse macrophage or human peripheral blood mononuclear cell supernatants, nor were any effects observed on IL-8‒induced human neutrophil chemotaxis. These in vitro results suggest that impediment of neutrophil infiltration by lefamulin in vivo may not occur through direct interaction with macrophages or neutrophilic chemotaxis. This is the first study to demonstrate inhibition of neutrophilic lung infiltration and reduction of pro-inflammatory cytokine/chemokine concentrations by clinically relevant lefamulin doses. This anti-inflammatory activity may be beneficial in patients with acute respiratory distress syndrome, cystic fibrosis, or severe inflammation-mediated lung injury, similar to glucocorticoid (eg, dexamethasone) activity. Future lefamulin anti-inflammatory/immunomodulatory activity studies are warranted to further elucidate mechanism of action and evaluate clinical implications.

PMID:34587166 | DOI:10.1371/journal.pone.0237659

J Clin Psychol Med Settings. 2021 Sep 29. doi: 10.1007/s10880-021-09825-w. Online ahead of print.

ABSTRACT

Experiences of anxiety and depression are common in adults with Cystic Fibrosis (AwCF) (e.g. Quittner in Thorax 69:1090-1097, 2014) and may impact on a wide range of important health-related behaviours, such as adherence to medication and timely attendance for medical review when experiencing pulmonary exacerbation. Common screening measures used in CF such as the PHQ-9 and GAD-7 may reflect an absence of anxiety or depression when clinically significant emotional difficulties are apparent on further assessment. This study preliminarily validated the previously developed Distress in Cystic Fibrosis Scale (DCFS) (Patel in Journal of Cystic Fibrosis 15:S26, 2016); a 23-item questionnaire to assess psychosocial distress in AwCF. Inpatient and outpatient participants with CF (N = 119) completed a battery of questionnaires, including the DCFS. PCA results supported a single component model. The DCFS showed high internal consistency and correlated significantly with measures of mood and quality of life. The DCFS shows promise as a screening tool to assess clinically significant psychosocial distress in an adult CF population.

PMID:34586547 | DOI:10.1007/s10880-021-09825-w

Microbiol Spectr. 2021 Sep 29:e0118621. doi: 10.1128/Spectrum.01186-21. Online ahead of print.

ABSTRACT

Carbapenem resistance in Pseudomonas aeruginosa strains responsible for chronic lung infections in cystic fibrosis (CF) patients is mainly due to loss of the OprD protein and, limited to meropenem and doripenem, to overexpression of efflux pumps. However, recent reports of isolates showing inconsistent genotype-phenotype combinations (e.g., susceptibility in the presence of resistance determinants and vice versa) suggest the involvement of additional factors whose role is not yet fully elucidated. Among them, the OpdP porin as an alternative route of entry for carbapenems other than OprD and the overexpression of two chromosomal carbapenemases, the Pseudomonas-derived cephalosporinase (PDC) and the PoxB oxacillinase, have recently been reconsidered and studied in specific model strains. Here, the contribution of these factors was investigated by comparing different phenotypic variants of three strains collected from the sputum of colonized CF patients. Carbapenem uptake through OpdP was investigated both at the functional level, by assessing the competition exerted by glycine-glutamate, the OpdP's natural substrate, against imipenem uptake, and at the molecular level, by comparing the expression levels of opdP genes by quantitative real-time PCR (qRT-PCR). Moreover, overexpression of the chromosomal carbapenemases in some of the isolates was also investigated by qRT-PCR. The results showed that, even if OprD inactivation remains the most important determinant of carbapenem resistance in strains infecting the CF lung, the interplay of other determinants might have a nonnegligible impact on bacterial susceptibility, being able to modify the phenotype of part of the population and consequently complicating the choice of an appropriate therapy. IMPORTANCE This study examines the interplay of multiple factors in determining a pattern of resistance or susceptibility to carbapenems in clinical isolates of Pseudomonas aeruginosa, focusing on the role of previously poorly understood determinants. In particular, the impact of carbapenem permeability through OprD and OpdP porins was analyzed, as well as the activity of the chromosomal carbapenemases AmpC and PoxB, going beyond the simple identification of resistance determinants encoded by each isolate. Indeed, analysis of the expression levels of these determinants provides a new approach to determine the contribution of each factor, both individually and in coexistence with the other factors. The study contributes to understanding some phenotype-genotype discordances closely related to the heteroresistance frequently detected in P. aeruginosa isolates responsible for pulmonary infections in cystic fibrosis patients, which complicates the choice of an appropriate patient-specific therapy.

PMID:34585948 | DOI:10.1128/Spectrum.01186-21

Pol J Microbiol. 2021 Sep;70(3):315-320. doi: 10.33073/pjm-2021-028. Epub 2021 Sep 17.

ABSTRACT

Mycobacterium chimaera is the newly described species belonging to Mycobacterium avium complex (MAC), with morphology and growth characteristics closely related to Mycobacterium intracellulare. The aim of this retrospective study was to analyze the frequency and clinical significance of M. chimaera identification in the population of patients with previous positive respiratory cultures for M. intracellulare or MAC. 200 strains of M. intracellulare or MAC, isolated from respiratory specimens of patients hospitalized in pulmonary wards, between 2011 and 2020, were retrospectively analyzed with GenoType NTM-DR test. 88 (44%) of strains were re-classified to M. chimaera species. Analysis of clinical data in 30 patients with positive M. chimaera isolates revealed that they were diagnosed with chronic obstructive pulmonary disease (COPD) - 27%, past tuberculosis - 20%, or interstitial lung diseases - 17%, respectively. Non-tuberculous mycobacterial lung disease (NTMLD) caused by M. chimaera has been recognized in 53% of patients, most often in those presenting with post-tuberculous lung lesions. M. chimaera was almost exclusively isolated from respiratory specimens of patients with underlying lung diseases, especially those with COPD and/or past tuberculosis. NTMLD due to M. chimaera was diagnosed predominantly in patients with past tuberculosis.

PMID:34584525 | PMC:PMC8458994 | DOI:10.33073/pjm-2021-028

J Cyst Fibros. 2021 Sep 25:S1569-1993(21)01416-8. doi: 10.1016/j.jcf.2021.09.011. Online ahead of print.

NO ABSTRACT

PMID:34583889 | DOI:10.1016/j.jcf.2021.09.011

Pediatr Pulmonol. 2021 Sep 28. doi: 10.1002/ppul.25701. Online ahead of print.

NO ABSTRACT

PMID:34583429 | DOI:10.1002/ppul.25701

Pediatr Pulmonol. 2021 Sep 28. doi: 10.1002/ppul.25708. Online ahead of print.

ABSTRACT

INTRODUCTION: The COVID-19 pandemic has accelerated the move towards home spirometry monitoring, including in children. Our aim was to determine whether the remote supervision of spirometry by a physiologist improves the technical quality and failure rate of the manoeuvres.

METHOD: Children with cystic fibrosis who had been provided with NuvoAir home spirometers were randomly allocated to either supervised or unsupervised home spirometry following a detailed training session. Home spirometry was performed every 2 weeks for 12 weeks. Tests were assigned a quality factor (QF) using our laboratory grading system as per ATS/ERS standards, with tests marked from A to D, or Fail. In our laboratory we aim for QF A in all spirometry tests, but report results of QF B or C with a cautionary note. QF A was therefore the primary outcome, and QF A-C the secondary outcome.

RESULTS: 61 patients were enrolled; 166 measurements were obtained in the supervised group, and 153 in the unsupervised group. Significantly more measurements achieved QF A in the supervised compared to unsupervised group (89% vs 74%; p= <0.001) whilst proportions reaching grade A-C were similar (99% vs 95%; p=0.1). All significant declines in spirometry results had a clinical rather than technical reason. Family/patient feedback for both arms was very positive.

CONCLUSION: These results suggest that home spirometry in children should ideally be remotely supervised by a physiologist, but acceptable results can be obtained if resources do not allow this, provided that training is delivered and results monitored according to our protocol. This article is protected by copyright. All rights reserved.

PMID:34581507 | DOI:10.1002/ppul.25708

J Pak Med Assoc. 2021 Sep;71(9):2217-2223. doi: 10.47391/JPMA.04-515.

ABSTRACT

OBJECTIVE: To ascertain major risk factors associated with pulmonary exacerbation and pulmonary function decline in cystic fibrosis.

METHODS: The systematic review was conducted at Aga Khan University, Karachi, in September 2018, and comprised electronic search of PubMed, Ovid, Science Direct and Cumulative Index of Nursing and Allied Health Literature databases of studies conducted from January 1990 to September 2018 which were categorised into 3 sets; 1990-98, 1999-2007 and 2008-18. Studies included for review focussed on articles with pulmonary exacerbation as the health outcome indicator, and had diagnosis of cystic fibrosis as the inclusion criteria, while risk factors were the exposure terms used in the search process. References in bibliographies of the included studies were also systematically searched for relevant documents.

RESULTS: Of the 60 studies obtained, 31(51.7%) were selected; 2(6.45%) from 1990-98, 7(22.58%) from 1999-2007 and 22(70.96%) from 2008-18. Overall, 17(54.83%) were cohort studies, 7(22.5%) were cross-sectional studies, 3(9.6%) were case-control studies, 3(9.6%) were randomised controlled trials and 1(3.2%) was systematic review and meta-analysis. In terms of major risk factors, genetic mutations were cited by 4(12.9%) studies, infections and inflammatory biomarkers by 15(48.4%), nutritional deficiencies by 9(29%) and geographical and socioeconomic status by 3(9.6%) studies.

CONCLUSIONS: Early identification and recognition of risk factors associated with pulmonary exacerbation can have an explicit impact on its management, leading to decreased morbidity and mortality burden in cystic fibrosis cases.

PMID:34580518 | DOI:10.47391/JPMA.04-515

J Cyst Fibros. 2021 Sep 24:S1569-1993(21)01344-8. doi: 10.1016/j.jcf.2021.08.003. Online ahead of print.

ABSTRACT

The approval and subsequent reimbursement of CFTR modulator therapies from 2012 have provided a potential "game-changing" treatment for patients with cystic fibrosis (CF), especially among younger patients. We used HCUP-NIS and HCUP-KID data in 2006, 2009, 2012 and 2016 to compare the number of admissions, hospital charges/cost, length of stay (LOS) and other clinical outcomes between inpatient admissions aged over and below 20 with CF before and after the approval of CFTR therapies. We found the number of hospitalizations with CF dropped among those aged 0-20 but increased among those aged over 20. We found the average LOS and charges/costs increased among the former and decreased among the later. These findings support the hypothesis that modulator therapies have impacted on patterns of hospital care, contributing to a reduction in the number of young people treated in hospital albeit with an increase in their complexity relative to those aged over 20.

PMID:34580033 | DOI:10.1016/j.jcf.2021.08.003

Clin Radiol. 2021 Sep 24:S0009-9260(21)00442-6. doi: 10.1016/j.crad.2021.09.008. Online ahead of print.

ABSTRACT

AIM: To assess image quality and dose-reduction efficacy of model-based iterative reconstruction (MBIR) in computed tomography (CT) of the paranasal sinus (CTPNS) compared with adaptive statistical iterative reconstruction (ASIR) in cystic fibrosis (CF) patients.

MATERIALS AND METHODS: Unenhanced CTPNS studies performed in adult CF patients from 2014 to 2020 were included. MBIR and ASIR were used and compared. Two radiologists assessed the CT images blindly and randomly. Quantitative assessment of noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) was performed in the maxillary sinus, sphenoid body, temporalis, and background air. Qualitative assessment performed included image sharpness, noise and contrast.

RESULTS: Thirty-seven MBIR and 45 ASIR CT PNS studies were included. MBIR achieved a 74% effective median dose reduction (0.039 mSv) compared with ASIR (0.147 mSv). Measured noise was significantly lower in all regions using MBIR (p<0.001) with superior SNR (p<0.001). MBIR had higher CNR compared to ASIR (4.567 versus 2.03, p<0.001). MBIR images were sharper and less noisy, with equal contrast. Cohen's weighted kappa value was 0.824 for qualitative analysis, indicating good inter-rater agreement. Both methods had 100% diagnostic acceptability.

CONCLUSION: MBIR produces high-quality CTPNS images at a significantly lower dose compared with ASIR. It is the preferred imaging surveillance method in CF patients and may have roles in other patient cohorts.

PMID:34579861 | DOI:10.1016/j.crad.2021.09.008

mBio. 2021 Sep 28:e0209821. doi: 10.1128/mBio.02098-21. Online ahead of print.

ABSTRACT

Burkholderia cenocepacia is a member of the Burkholderia cepacia complex (Bcc), a group of bacteria with members responsible for causing lung infections in cystic fibrosis (CF) patients. The most severe outcome of Bcc infection in CF patients is cepacia syndrome, a disease characterized by necrotizing pneumonia with bacteremia and sepsis. B. cenocepacia is strongly associated with cepacia syndrome, making it one of the most virulent members of the Bcc. Mechanisms underlying the pathogenesis of B. cenocepacia in lung infections and cepacia syndrome remain to be uncovered. B. cenocepacia is primarily an intracellular pathogen and encodes the type VI secretion system (T6SS) effector TecA, which is translocated into host phagocytes. TecA is a deamidase that inactivates multiple Rho GTPases, including RhoA. Inactivation of RhoA by TecA triggers assembly of the pyrin inflammasome, leading to secretion of proinflammatory cytokines, such as interleukin-1β, from macrophages. Previous work with the B. cenocepacia clinical isolate J2315 showed that TecA increases immunopathology during acute lung infection in C57BL/6 mice and suggested that this effector acts as a virulence factor by triggering assembly of the pyrin inflammasome. Here, we extend these results using a second B. cenocepacia clinical isolate, AU1054, to demonstrate that TecA exacerbates weight loss and lethality during lung infection in C57BL/6 mice and mice engineered to have a CF genotype. Unexpectedly, pyrin was dispensable for TecA virulence activity in both mouse infection models. Our findings establish that TecA is a B. cenocepacia virulence factor that exacerbates lung inflammation, weight loss, and lethality in mouse infection models. IMPORTANCE B. cenocepacia is often considered the most virulent species in the Bcc because of its close association with cepacia syndrome in addition to its capacity to cause chronic lung infections in CF patients (1). Prior to the current study, virulence factors of B. cenocepacia important for causing lethal disease had not been identified in a CF animal model of lung infection. Results of this study describe a CF mouse model and its use in demonstrating that the T6SS effector TecA of B. cenocepacia exacerbates inflammatory cell recruitment and weight loss and is required for lethality and, thus, acts as a key virulence factor during lung infection. This model will be important in further studies to better understand TecA's role as a virulence factor and in investigating ways to prevent or treat B. cenocepacia infections in CF patients. Additionally, TecA may be the founding member of a family of virulence factors in opportunistic pathogens.

PMID:34579569 | DOI:10.1128/mBio.02098-21

Nutrients. 2021 Sep 18;13(9):3263. doi: 10.3390/nu13093263.

ABSTRACT

Breastfeeding (BF) is considered the normative standard of feeding for all infants. However, the impact of BF in patients with cystic fibrosis (CF) is not completely defined. Therefore, we conducted a systematic review to evaluate BF prevalence in the CF population and its impact on anthropometric and pulmonary outcomes. We searched MEDLINE, Embase and the Cochrane Library for original articles published in English up to 4 December 2020 that report the prevalence of BF and/or any measure of association between BF and anthropometric or pulmonary outcomes. Nine observational studies were identified (six retrospective cohort studies, one prospective cohort study, one survey and one case-control study within a retrospective cohort). The BF rate in CF patients is lower than that of the healthy population (approximately 50-60% of infants were breastfed at any time). The benefits in anthropometric outcomes of BF for >2 months in this at-risk population are unclear. A few relatively small studies suggest a potential benefit of BF in reducing lung infections, although data are inconsistent. The currently available data are insufficient to draw definite conclusions on the benefits of exclusive BF in anthropometric and pulmonary outcomes in CF. Clinical trials evaluating well-defined BF promotion interventions are needed.

PMID:34579139 | DOI:10.3390/nu13093263

Nutrients. 2021 Sep 15;13(9):3206. doi: 10.3390/nu13093206.

ABSTRACT

Although body mass index (BMI) is a potential risk factor for bronchiectasis in young adults, the association between BMI and incident bronchiectasis has not been well elucidated. This study included 6,329,838 individuals aged 20-40 years from the Korean National Health Insurance Service database 2009-2012 who were followed up until the date of the diagnosis of bronchiectasis, death, or 31 December 2018. We evaluated the incidence and risk of bronchiectasis according to the BMI category. The incidence rate of bronchiectasis increased as BMI decreased in a dose-dependent manner (p for trend <0.01). In multivariable Cox regression analysis, being underweight was an independent risk factor for the development of bronchiectasis, with a hazard ratio of 1.24 (95% confidence interval, 1.19-1.30) compared to being normal weight. In subgroup analysis, the effect of being underweight on the development of bronchiectasis was more evident in males and older individuals (30-40 years) than females and younger individuals (20-29 years), respectively (p for interaction <0.01 for both). These results remained significant in subgroup analysis in which subjects with comorbidities related to being underweight were excluded. Being underweight may be a novel risk factor for the development of bronchiectasis in young adults.

PMID:34579084 | DOI:10.3390/nu13093206

Nutrients. 2021 Aug 24;13(9):2907. doi: 10.3390/nu13092907.

ABSTRACT

Patients with cystic fibrosis (CF) are at increased risk of malnutrition and growth failure due to multiple factors as a result of suboptimal or absent function of the CFTR chloride channel protein. Dysfunctional CFTR contributes to increased energy expenditure, exocrine pancreatic insufficiency causing impaired dietary macronutrient digestion and absorption, intestinal dysbiosis, and impaired bile acid homeostasis. Poor nutritional status as a result of these mechanisms is associated with decreased lung function, worse clinical outcomes, and ultimately, increased mortality. Nutritional interventions addressing these mechanisms, such as pancreatic enzyme-replacement therapy and enteral caloric supplementation, have improved nutritional status and, by association, clinical outcomes. In the last decade, the advent of medications targeting defective CFTR proteins has revolutionized the care of patients with CF by reducing the overall impact of CFTR dysfunction. Below, we summarize the effects of highly effective CFTR modulators on nutritional status overall as well as specific factors including bile acid metabolism, pancreatic function, energy expenditure, and intestinal dysbiosis. The future of CF nutrition care will require a paradigm shift away from focusing on methods addressing CFTR dysfunction such as excess calorie provision and toward an individualized, holistic approach in the context of specific mutations and CFTR-directed therapy.

PMID:34578785 | DOI:10.3390/nu13092907

Pathogens. 2021 Sep 13;10(9):1177. doi: 10.3390/pathogens10091177.

ABSTRACT

Staphylococcus aureus is next to Pseudomonas aeruginosa the most isolated pathogen from the airways of cystic fibrosis (CF) patients, who are often infected by a dominant S. aureus clone for extended periods. To be able to persist, the pathogen has to adapt to the hostile niche of the airways to counteract host defence, antibiotic therapy and the competition with coinfecting pathogens. S. aureus is equipped with many virulence factors including adhesins, toxins that are localized on the chromosome, on plasmids or are phage-related. S. aureus is especially versatile and adaptation and evolution of the pathogen occurs by the acquisition of new genes by horizontal gene transfer (HGT), changes in nucleotides (single nucleotide variations, SNVs) that can cause a selective advantage for the bacteria and become fixed in subpopulations. Methicillin-resistant S. aureus are a special threat to CF patients due to the more severe lung disease occurring in infected patients. Today, with decreasing costs for sequencing, more and more studies using S. aureus isolates cultured from CF patients are being published, which use whole genome sequencing (WGS), multilocus sequence typing (MLST) or spa-sequence typing (spa-typing) to follow the population dynamics of S. aureus, elucidate the underlying mechanisms of phenotypic variants, newly acquired resistance or adaptation to the host response in this particular niche. In the first part of this review, an introduction to the genetic make-up and the pathogenesis of S. aureus with respect to CF is provided. The second part presents an overview of recent studies and their findings using genotypic methods such as single or multilocus sequencing and whole genome sequencing, which identify factors contributing to the adaptation of S. aureus and its evolution in the airways of individuals with CF.

PMID:34578208 | DOI:10.3390/pathogens10091177