[Bronchiectasis not related to cystic fibrosis in children: Guidelines for diagnosis, monitoring and treatment].

Arch Argent Pediatr. 2020 Dec;118(6):S164-S182

Authors: Comité de Neumonología

Abstract
Bronchiectasis is within the spectrum of chronic lung disease characterized by progressive and often irreversible bronchial dilation caused by structural changes in the bronchial wall and chronic inflammation of the airways. The cardinal symptom is persistent moist and productive chronic cough that should alert to timely intervention and interrupt the cycle of inflammation, infection, and airway damage. Early diagnosis through high-resolution computed tomography of the chest and clinical monitoring facilitate the implementation of intensive treatment that reduces and minimizes damage to the airway. Although current therapeutic actions for the management of bronchiectasis are effective, there are few randomized clinical trials in pediatrics. The objective of the document is to provide an update on the diagnosis, monitoring and treatment of bronchiectasis not related to cystic fibrosis in children.

PMID: 33231063 [PubMed - in process]

Pulmonary Manifestations of Genetic Disorders in Children.

Pediatr Clin North Am. 2021 Feb;68(1):1-24

Authors: Pletcher BA, Turcios NL

Abstract
Congenital bronchopulmonary malformations are relatively common and arise during various periods of morphogenesis. Although some are isolated or sporadic occurrences, others may result from single gene mutations or cytogenetic imbalances. Single gene mutations have been identified, which are etiologically related to primary pulmonary hypoplasia, lung segmentation defects as well as pulmonary vascular and lymphatic lesions. Functional defects in cystic fibrosis, primary ciliary dyskinesias, alpha-1-antitrypsin deficiency, and surfactant proteins caused by gene mutations may result in progressive pulmonary disease. This article provides an overview of pediatric pulmonary disease from a genetic perspective.

PMID: 33228926 [PubMed - in process]

Proteomic Studies of the Biofilm Matrix including Outer Membrane Vesicles of Burkholderia multivorans C1576, a Strain of Clinical Importance for Cystic Fibrosis.

Microorganisms. 2020 Nov 19;8(11):

Authors: Terán LC, Distefano M, Bellich B, Petrosino S, Bertoncin P, Cescutti P, Sblattero D

Abstract
Biofilms are aggregates of microbial cells encased in a highly hydrated matrix made up of self-produced extracellular polymeric substances (EPS) which consist of polysaccharides, proteins, nucleic acids, and lipids. While biofilm matrix polysaccharides are unraveled, there is still poor knowledge about the identity and function of matrix-associated proteins. With this work, we performed a comprehensive proteomic approach to disclose the identity of proteins associated with the matrix of biofilm-growing Burkholderia multivorans C1576 reference strain, a cystic fibrosis clinical isolate. Transmission electron microscopy showed that B. multivorans C1576 also releases outer membrane vesicles (OMVs) in the biofilm matrix, as already demonstrated for other Gram-negative species. The proteomic analysis revealed that cytoplasmic and membrane-bound proteins are widely represented in the matrix, while OMVs are highly enriched in outer membrane proteins and siderophores. Our data suggest that cell lysis and OMVs production are the most important sources of proteins for the B. multivorans C1576 biofilm matrix. Of note, some of the identified proteins are lytic enzymes, siderophores, and proteins involved in reactive oxygen species (ROS) scavenging. These proteins might help B. multivorans C1576 in host tissue invasion and defense towards immune system assaults.

PMID: 33228110 [PubMed]

Role Of Long-Term Intermittent Use Of Oral Azithromycin On Pulmonary Exacerbations In Cystic Fibrosis Children.

J Ayub Med Coll Abbottabad. 2020 Oct-Dec;32(4):429-434

Authors: Aziz DA, Shahid S, Iftikhar H, Mir F

Abstract
Background: Pulmonary exacerbation is the most common acute event occurring in a patient with cystic fibrosis and Pseudomonas aeruginosa is the most commonly involved organism. Azithromycin has antimicrobial and immunomodulatory effects on the lungs and our study aimed to determine the role of long-term intermittent use of oral azithromycin on pulmonary exacerbations in children with cystic fibrosis.
Methods: A retrospective cohort study was conducted from January 2012 to December 2016 at a tertiary care hospital, Aga Khan University Hospital, Karachi. The criteria for enrolment included cystic fibrosis patients aged 3-18 years who were classified into two groups based on their antibiotic use. The Azithromycin group included those CF patients who were on three days per week oral Azithromycin (10 mg per Kg per day) for 6 months. The non-azithromycin group included CF patients who were not on long term oral azithromycin. Our primary outcome was to assess the reduction in the number of exacerbations.
Results: Sixty-three patients with a mean age (10.06±3.80) and mean pulmonary exacerbations of (3.67±1.58) in the 6 months before enrolment were included in our study. Out of these, 30 patients were included in the azithromycin group and 33 patients in the non-azithromycin group. Overall, 180 exacerbations were documented during the study period. The one-way ANOVA (F (1,61) =8.033, p<0.05) demonstrated a statistically significant difference in the mean number of exacerbations between the azithromycin (2.70±1.72) and non-azithromycin group (3.81±1.40) however, the mean length of stay between the groups was not significant (p=0.582). P. aeruginosa was found to be the most predominant colonizer of the airways.
Conclusion: Long term low dose azithromycin therapy is beneficial in young patients with cystic fibrosis. It is an effective prevention strategy for pulmonary exacerbations.

PMID: 33225638 [PubMed - in process]

Re: The outcome of pregnancy in women with cystic fibrosis: a UK population-based descriptive study.

BJOG. 2020 Nov 23;:

Authors: Duckers J, Schlueter D, Phillips R, Cosgriff R, Esan O, Paranjothy S, Williams D, Norman R, Taylor Robinson D, Carr S

PMID: 33225530 [PubMed - as supplied by publisher]

Megacystis-microcolon-intestinal hypoperistalsis syndrome associated with cystic fibrosis and meconium peritonitis in a female neonate 4 days of age - case report and review of the literature.

Med Pharm Rep. 2020 Oct;93(4):422-427

Authors: Surd A, Gheban D, Mironescu A, Aldea C, Gocan H

Abstract
We present a case of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) in a four days old female infant who presented with abdominal distension, bilious vomiting, massive hematuria and feeding intolerance which was first interpreted as Prune Belly Syndrome (PBS), referred to our department after iatrogenic gastric and colonic perforation. Berdon syndrome or MMIHS is a rare congenital anomaly characterized by a massive enlarged bladder, distended abdomen, microcolon, functional obstruction of the gastrointestinal tract, and malrotation.

PMID: 33225270 [PubMed]

Urban Life as Risk Factor for Aspergillosis.

Front Cell Infect Microbiol. 2020;10:601834

Authors: Grehn C, Eschenhagen P, Temming S, Düesberg U, Neumann K, Schwarz C

Abstract
Aspergillus fumigatus (Af) frequently colonizes the airways of patients with cystic fibrosis (CF) and can cause severe diseases, such as allergic bronchopulmonary aspergillosis, Af bronchitis or even Af pneumonia. However, risk factors, including environmental factors, for acquiring Af in the respiratory tract of patients with CF are rarely studied and described. The aim of this study was to investigate whether urban or rural life could affect colonization with Af in the respiratory tract of patients with CF. Due to privacy policy, registry data are usually not linked to patients´ home addresses. It is therefore very difficult to analyze the influence of the patient´s residential environment. This prospective questionnaire survey was carried out in 31 German CF centers in 2018. Only completed surveys, including a clearly assigned type of residential area were included. Statistical analysis was performed by chi-squared test and logistic regression models. A total of 1016 questionnaires were analyzed (Patients` age: 23 ± 13; 0-88 years; female gender: n=492; 48%). The majority of patients with CF live in large cities (n =314; 30.9%) or urban districts (n=461; 45.4%). Prevalence of 30.2% was found for Af, within the 12 months of investigation period. Af colonization was significantly associated with urban life (p=0.004). Urban live should be considered as possible new risk factor for colonization with Af in the respiratory tract of patients with CF. These new results may raise the awareness of the influence of environmental factors on patient outcomes and should be included in patient guidance and preventive measures.

PMID: 33224902 [PubMed - in process]

Effects of rehabilitation methods on lower-limb muscle function and functional performance in patients with cystic fibrosis: A systematic review.

Clin Rehabil. 2020 Nov 23;:269215520972941

Authors: Poncin W, Evrard S, Mareschal A, Gohy S, Reychler G

Abstract
OBJECTIVE: To investigate the effects of rehabilitation methods on leg muscle function and functional performance in cystic fibrosis.
DATA SOURCES: A literature search was conducted in PubMed (MEDLINE), Scopus and the Cochrane Library from inception to October 12, 2020. A secondary hand search through reference lists from identified articles was conducted.
REVIEW METHODS: Three authors independently checked the full-text copies for eligibility of relevant articles. Randomized controlled trials were included. Methodological quality was assessed using the Physiotherapy Evidence Database scale. The PRISMA guidelines were followed. Results suggestive of leg muscle function (e.g. strength, power, endurance, and fatigue) and functional performance were reported.
RESULTS: The search identified 8 studies (233 patients). The overall quality of these articles was good. Rehabilitation modalities investigated were physical exercises (aerobic, anaerobic and resistance training) (n = 7) and neuromuscular electrical stimulation (n = 1). Most studies (n = 4) reported on the effects of combined aerobic and resistance training and showed improvement on leg strength when exercises were supervised. Aerobic training alone or the use of neuromuscular electrical stimulation also enhanced leg strength, whereas anaerobic training did not. Two studies evaluated leg fatigue and found no improvement compared to standard care. One study assessed the effect of exercises on functional performance and found no improvement when compared to standard care. No studies emphasized the impact of rehabilitation methods on leg muscle endurance or power.
CONCLUSION: Combined aerobic and resistance training enhances leg muscle strength in cystic fibrosis. There is insufficient data on other leg muscle outcomes, nor on alternative rehabilitation strategies.

PMID: 33222526 [PubMed - as supplied by publisher]

Anakinra combined with methylprednisolone in patients with severe COVID-19 pneumonia and hyperinflammation: an observational cohort study.

J Allergy Clin Immunol. 2020 Nov 18;:

Authors: Bozzi G, Mangioni D, Minoia F, Aliberti S, Grasselli G, Barbetta L, Castelli V, Palomba E, Alagna L, Lombardi A, Ungaro R, Agostoni C, Baldini M, Blasi F, Cesari M, Costantino G, Fracanzani AL, Montano N, Monzani V, Pesenti A, Peyvandi F, Sottocorno M, Muscatello A, Filocamo G, Gori A, Bandera A

Abstract
BACKGROUND: Immunomodulants have been proposed to mitigate SARS-Cov-2-induced cytokine storm, which drives acute respiratory distress syndrome in COVID-19.
OBJECTIVE: To determine efficacy and safety of the association of IL-1 receptor antagonist anakinra plus methylprednisolone in severe COVID-19 pneumonia with hyperinflammation.
METHODS: Secondary analysis of prospective observational cohort studies at an Italian tertiary health-care facility. COVID-19 patients consecutively hospitalized (02/25/2020 to 03/30/2020), with hyperinflammation (ferritin ≥1000ng/mL and/or C-reactive protein >10mg/dL) and respiratory failure (oxygen therapy from 0.4 FiO2 Venturi mask to invasive mechanical ventilation) were evaluated to investigate the effect of high-dose anakinra plus methylprednisolone on survival. Patients were followed from study inclusion to day 28 or death. Crude and adjusted (sex, age, baseline PaO2:FiO2 ratio, Charlson Index, baseline mechanical ventilation, hospitalization to inclusion lapse) risks were calculated (Cox proportional regression model).
RESULTS: 120 COVID-19 patients with hyperinflammation (median age 62 years, 80.0% males, median PaO2:FiO2 ratio 151, 32.5% on mechanical ventilation) were evaluated. Of these, 65 were treated with anakinra and methylprednisolone and 55 were untreated historical controls. At 28 days, mortality was 13.9% in treated patients and 35.6% in controls (Kaplan-Meier plots, p=0.005). Unadjusted and adjusted risk of death was significantly lower for treated patients compared to controls (HR 0.33 (95%CI 0.15-0.74), p=0.007 and HR 0.18 (95%CI 0.07-0.50), p=0.001, respectively). No significant differences in bloodstream infections or laboratory alterations were registered.
CONCLUSIONS: Treatment with anakinra plus methylprednisolone may be a valid therapeutic option in COVID-19 patients with hyperinflammation and respiratory failure, also on mechanical ventilation. Randomized, controlled trials including use of either agent alone are needed to confirm these results.

PMID: 33220354 [PubMed - as supplied by publisher]

Cystic Fibrosis with Non-G551D Gating Mutations in Italy: Epidemiology and clinical characteristics.

Pediatr Pulmonol. 2020 Nov 20;:

Authors: Salvatore D, Carnovale V, Majo F, Padoan R, Salvatore M, Taruscio D, Amato A, Ferrari G, Campagna G

Abstract
BACKGROUND: CFTR gating mutations (GMs) result in CFTR that is present at the cell surface but non-functional. Patients with the G551D mutation, the most prevalent worldwide have been well studied. Italian GM patients have mainly non-G551D mutations. We studied their epidemiology and clinical characteristics in the period spanning the pre/post ivacaftor introduction to the Italian market.
METHODS: Data from the Italian CF Registry were used to describe patients with GMs and compare them with F508del homozygous (F/F) patients.
RESULTS: 186 patients with GMs (median (range) age 21.96 (0.13 to 63.38) years) were identified among the 5,552 patients included in the study (3.3%). They had lower sweat chloride values (SCV) at diagnosis than the F/F and lower ratio of males. In the GM group, examining the data of the years 2012 and 2017 and comparing with F/F, lung infection by Staphylococcus aureus and diabetes became less prevalent, and better FEV1 and nutritional status were observed in 2017. The cross-sectional evaluation year-by-year from 2012 to 2017 of the GM group showed improving trends in lung function and BMI, and decreasing prevalence of diabetes compared with F/F. Longitudinal evaluation of GM patients showed improvement in ppFEV1 and nutrition in the 2012-2017 period. These variations correspond to the introduction of treatment with the CFTR potentiator ivacaftor (2014/2015).
CONCLUSIONS: Italian patients with GMs are few and are characterised by milder phenotypes than F/F patients. Improved outcomes are likely influenced by treatment with ivacaftor. This article is protected by copyright. All rights reserved.

PMID: 33219628 [PubMed - as supplied by publisher]

Lung Recruitability of COVID-19 Pneumonia in Patients Undergoing Helmet CPAP.

Arch Bronconeumol. 2020 Oct 22;:

Authors: Amati F, Aliberti S, Misuraca S, Simonetta E, Bindo F, Vigni A, Bassi L, Mazzucco A, Cara A, Blasi F

PMID: 33218783 [PubMed - as supplied by publisher]

Effectiveness of Short versus Long Course Perioperative Antibiotics in Lung Transplant Recipients with Donor Positive Respiratory Cultures.

Transpl Infect Dis. 2020 Nov 20;:e13518

Authors: Groff LT, Reed EE, Coe KE, El Boghdadly Z, Keller BC, Whitson BA, Burcham PK

Abstract
Lung transplant recipients are at increased risk for infection in the early postoperative phase, thus perioperative antibiotics are employed. This retrospective study evaluated the efficacy of short vs long course perioperative antibiotics in lung transplant patients. Lung transplant patients with donor positive cultures between Aug 2013 and Sept 2019 were evaluated, excluding those with cystic fibrosis, death within 14 days and re-transplants. The primary outcome was 30-day freedom from donor-derived respiratory infection. A total of 147 patients were included (57 short vs 90 long course). Median perioperative antibiotic duration was 6 days in the short course vs. 14 days in the long course group (p< 0.0001). Thirty-day freedom from donor-derived respiratory infection was present in 56 (98%) patients in the short course vs. 85 (94%) patients in the long course group (p= 0.41). There was no difference in development of Clostridioides difficile infections (p = 0.41), while cumulative ventilator time and time to post-op extubation were longer in the long course group (p = 0.001 and 0.004, respectively). Among lung transplant recipients with positive donor respiratory cultures, short course perioperative antibiotics were as effective as long course antibiotics in preventing donor-derived bacterial respiratory infections.

PMID: 33217132 [PubMed - as supplied by publisher]

Prevalence of coccidioidomycosis in cystic fibrosis patients residing in Southern Arizona.

Med Mycol. 2020 Nov 19;:

Authors: Estrada L, August J, Ojo T, Campion J

Abstract
Sparse data exists about patients with cystic fibrosis (CF) and their risk of contracting coccidioidiomycosis or Valley Fever, which is highly endemic in southern Arizona. A retrospective review of medical records of 79 adult CF patients residing in Arizona was performed. Two cases only of coccidioidomycosis were documented between in the 790 patient years. However, false-positive serologies were found in 15 patients. This 10-year retrospective review of 79 adult CF patients found that there was a lower prevalence of coccidioidomycosis in CF patients compared to that of the general population of the area.
LAY SUMMARY: Patients with cystic fibrosis (CF) suffer from chronic lung infection. Little is known about CF and fungal infection. Coccidioidomycosis is a fungal infection common in Arizona and this study shows a lower infection rate from Coccidioidomycosis in CF patients compared to the general population.

PMID: 33216128 [PubMed - as supplied by publisher]

Introduction.

Intern Med J. 2020 Nov;50(11):1403

Authors: Wilson J

PMID: 33215838 [PubMed - in process]

Management of Cepacia Syndrome With a Combination of Intravenous and Inhaled Antimicrobials in a Non-Cystic Fibrosis Pediatric Patient.

J Pediatr Pharmacol Ther. 2020;25(8):730-734

Authors: Branstetter JW, Yarbrough A, Poole C

Abstract
Burkholderia cepacia complex (Bcc) is an opportunistic pathogen, posing little risk to healthy individuals. The presentation of Bcc can vary from a virtually asymptomatic chronic infection, to an acute, life-threatening necrotizing pneumonia, acute respiratory distress syndrome, and bacteremia (cepacia syndrome) associated with a mortality rate up to 75%. We present the successful treatment of a 17-year-old male with chronic granulomatous disorder who presented with cepacia syndrome and confirmed Bcc pneumonia using a novel antimicrobial approach. Despite initial IV antimicrobial therapy, our patient continued to decline, developing hypotension requiring pressor support and eventually extracorporeal membrane oxygenation. An aggressive, multimechanistic approach including the combination of nebulized tobramycin, IV sulfamethoxazole-trimethoprim, ceftazidime, enteral minocycline, and corticosteroids was implemented. This multimechanistic antimicrobial approach in combination with systemic corticosteroids led to the successful treatment of cepacia syndrome in the setting of necrotizing pneumonia due to B cepacia with full respiratory recovery. We suggest that in patients with cepacia syndrome who continue to decline despite IV antimicrobial therapy, using multiple antimicrobial mechanisms of action may improve clinical outcomes.

PMID: 33214785 [PubMed]

Evaluation of Inhaled Tobramycin in Early Eradication of Pseudomonas aeruginosa in Infants With Cystic Fibrosis.

J Pediatr Pharmacol Ther. 2020;25(8):709-716

Authors: Choi J, Novak K, Thompson R

Abstract
OBJECTIVE: Early antibiotic therapy has the potential to eradicate initial Pseudomonas aeruginosa infection and postpone chronic infection. There are limited data evaluating the efficacy and safety of inhaled tobramycin in patients with cystic fibrosis (CF) who are younger than 1 year. The objective of this study was to evaluate the effectiveness of inhaled tobramycin in early eradication of P aeruginosa in infants with CF.
METHODS: This retrospective study evaluated patients with CF younger than 1 year with first time infection with P aeruginosa. The primary outcome was the frequency of P aeruginosa eradication. Secondary outcomes were sustained culture negativity at 12 and 18 months and safety assessments.
RESULTS: Of 18 patients included in the study, 9 received inhaled tobramycin and an enteral fluoroquinolone and 9 received inhaled tobramycin alone. Microbiologic clearance of respiratory cultures was observed in 83% patients at end of therapy and 78% of patients at 1 month posttherapy. Eradication of P aeruginosa was observed in 56% of patients at 6 months posttreatment with sustained culture negativity observed in 39% of patients up to 18 months.
CONCLUSIONS: Inhaled-tobramycin therapy is effective in early eradication of P aeruginosa infection and is well tolerated in infants younger than 1 year.

PMID: 33214782 [PubMed]

Pseudomonas aeruginosa adaptation and evolution in patients with cystic fibrosis.

Nat Rev Microbiol. 2020 Nov 19;:

Authors: Rossi E, La Rosa R, Bartell JA, Marvig RL, Haagensen JAJ, Sommer LM, Molin S, Johansen HK

Abstract
Intense genome sequencing of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) airways has shown inefficient eradication of the infecting bacteria, as well as previously undocumented patient-to-patient transmission of adapted clones. However, genome sequencing has limited potential as a predictor of chronic infection and of the adaptive state during infection, and thus there is increasing interest in linking phenotypic traits to the genome sequences. Phenotypic information ranges from genome-wide transcriptomic analysis of patient samples to determination of more specific traits associated with metabolic changes, stress responses, antibiotic resistance and tolerance, biofilm formation and slow growth. Environmental conditions in the CF lung shape both genetic and phenotypic changes of P. aeruginosa during infection. In this Review, we discuss the adaptive and evolutionary trajectories that lead to early diversification and late convergence, which enable P. aeruginosa to succeed in this niche, and we point out how knowledge of these biological features may be used to guide diagnosis and therapy.

PMID: 33214718 [PubMed - as supplied by publisher]

Draft Genome Sequence of Mycobacteroides sp. Strain LB1, Isolated from the Sputum of a Cystic Fibrosis Patient.

Microbiol Resour Announc. 2020 Nov 19;9(47):

Authors: Menzel P, Schwarzer R, Helmuth J, Friesen I

Abstract
We report the draft genome sequence of Mycobacteroides sp. strain LB1, isolated from the sputum of a cystic fibrosis patient in Berlin, Germany. The genome size is 4.9 Mbp with a GC content of 63.8%. The genome is only distantly related to other Mycobacteroides species, suggesting that it may represent a novel species.

PMID: 33214293 [PubMed]

Small molecule drugs in cystic fibrosis.

Arch Dis Child Educ Pract Ed. 2020 Nov 19;:

Authors: Hine C, Nagakumar P, Desai M

PMID: 33214241 [PubMed - as supplied by publisher]

Recommendations to improve physical activity prescription for the cystic fibrosis population: an Irish perspective.

BMC Health Serv Res. 2020 Nov 19;20(1):1052

Authors: Hurley N, Kehoe B, McCaffrey N, Redmond K, Cullen L, Moyna NM

Abstract
BACKGROUND: Physical activity (PA) is a well-established therapeutic modality for the maintenance and improvement of long-term health in cystic fibrosis (CF). Healthcare professionals (HCP) are considered credible and well-placed messengers for the delivery of PA advice. Limited research exists investigating the extent of PA prescription within CF care. This study aimed to identify Irish HCP i) knowledge and practice of, and ii) motivators and barriers to PA prescription, and iii) proposed strategies to optimize PA promotion and prescription in CF populations.
METHODS: HCP from six designated CF centres in Ireland and members of the national physiotherapy CF clinical interest group were invited to participate. Following an expression of interest, each HCP (n = 81) received an email containing the plain language statement and link to the online survey. 48 HCP (physiotherapists n = 24, other n = 24) completed the 30-item investigator-developed survey, which included multiple choice single answer, matrix style and open-ended questions.
RESULTS: Most HCP (81%) acknowledged that discussing PA with CF patients was part of their professional role. Almost all physiotherapists (95%) reported having sufficient knowledge regarding PA prescription, compared to 17% of other HCP. All physiotherapists reported discussing PA at every patient interaction, with 81% employing the current consensus guidelines, compared to 33 and 5% of other HCP, respectively. Among the most common barriers reported by HCP to recommending PA to their CF patients were; lack of motivation and compliance among patients to adhere to PA advice, limited availability of PA programmes to refer their patients to, limited time with patients during clinic visits and a lack of knowledge regarding PA prescription for CF care. Three-quarters of HCP reported a need to improve PA services for CF patients in Ireland.
CONCLUSION: As people with CF are living longer, it is imperative that HCP are expanding their scope of practice to include discussions around PA at every patient visit. Formal educational opportunities in the form of continuing professional development programmes are warranted for CF HCP to optimize long-term patient management and outcomes. There is also a need to develop patient-centered and evidence-based PA programmes underpinned by theories of behaviour change to enhance motivation and compliance among CF patients.

PMID: 33213453 [PubMed - in process]