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BACKGROUND AND AIM: In cystic fibrosis, gastrointestinal dysfunction and lower airway infection occur early and are independently associated with poorer outcomes in childhood. This study aimed to define the relationship between the microbiota at each niche during the first 2â years of life, its association with growth and airway inflammation, and explanatory features in the metabolome. MATERIALS AND METHODS: 67 bronchoalveolar lavage fluid (BALF), 62 plasma and 105 stool samples were collected from 39 infants with cystic fibrosis between 0 and 24â months who were treated with prophylactic antibiotics. 16S rRNA amplicon and shotgun metagenomic sequencing were performed on BALF and stool samples, respectively; metabolomic analyses were performed on all sample types. Sequencing data from healthy age-matched infants were used as controls. RESULTS: Bacterial diversity increased over the first 2â years in both BALF and stool, and microbial maturation was delayed in comparison to healthy controls from the RESONANCE cohort. Correlations between their respective abundance in both sites suggest stool may serve as a noninvasive alternative for detecting BALF Pseudomonas and Veillonella. Multisite metabolomic analyses revealed age- and growth-related changes, associations with neutrophilic airway inflammation, and a set of core systemic metabolites. BALF Pseudomonas abundance was correlated with altered stool microbiome composition and systemic metabolite alterations, highlighting a complex gut-plasma-lung interplay and new targets with therapeutic potential. CONCLUSION: Exploration of the gut-lung microbiome and metabolome reveals diverse multisite interactions in cystic fibrosis that emerge in early life. Gut-lung metabolomic links with airway inflammation and Pseudomonas abundance warrant further investigation for clinical utility, particularly in non-expectorating patients.
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Líquido da Lavagem Broncoalveolar , Fibrose Cística , Fezes , Microbioma Gastrointestinal , Pulmão , RNA Ribossômico 16S , Humanos , Fibrose Cística/microbiologia , Fibrose Cística/metabolismo , Lactente , Líquido da Lavagem Broncoalveolar/microbiologia , Fezes/microbiologia , Masculino , Feminino , RNA Ribossômico 16S/genética , Pulmão/microbiologia , Pulmão/metabolismo , Recém-Nascido , Estudos Longitudinais , Estudos de Casos e Controles , Metaboloma , Metabolômica , Antibacterianos/uso terapêutico , Pré-EscolarRESUMO
In response to the COVID-19 pandemic telehealth utilisation amongst the Cystic Fibrosis (CF) population increased. Our aim was to assess the impact of CF telehealth clinics on CF outcomes. We conducted a retrospective chart review of patients seen in the CF clinic at the Royal Children's Hospital (Victoria, Australia). In this review we compared spirometry, microbiology and anthropometry in the year preceding the pandemic to during the pandemic, and to the first in-person appointment in 2021. 214 patients were included. First in-person FEV1 was median 5.4% below individuals' best FEV1 in 12 months prior to lockdown and decreased by >10% in 46 (31.9%) patients. There were no significant findings with regards to microbiology or anthropometry. The reduction in FEV1 observed on return to in-person appointments highlights the importance of ongoing improvement of telehealth-based care along with continued face-to-face review for the paediatric CF population.
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COVID-19 , Fibrose Cística , Telemedicina , Humanos , Criança , Fibrose Cística/diagnóstico , Fibrose Cística/epidemiologia , Fibrose Cística/terapia , Estudos Retrospectivos , Pandemias , COVID-19/epidemiologia , Controle de Doenças TransmissíveisRESUMO
Neuromuscular scoliosis is a common feature in children with severe neurological impairment (SNI), including those with severe cerebral palsy. Surgical correction of scoliosis is the mainstay of treatment. This group of patients also have associated medical complexity. The complication rates post-surgery are high, although, for many, they are worth the risk. There are currently no published practice guidelines or care pathways for children with SNI who are undergoing scoliosis corrective surgery. In response to the high uptake of this surgery, coupled with the expected complication rates, our hospital established a perioperative clinic. The purpose of this paper is to describe our perioperative approach. This clinic has developed into a service beyond perioperative care and, with the collaborative meeting, enables shared decision-making to identify the right candidate for surgery. The process involves surgical expertise, understanding the family and child at the centre, and optimisation of medical care pre- and post-surgery. In this paper, we describe the process in a step-by-step manner. We provide clinical vignettes, as well as the proformas that we use, and we highlight the benefits of the team-based process.
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Survival statistics, estimated using data from national cystic fibrosis (CF) registries, inform the CF community and monitor disease progression. This study aimed to estimate survival among people with CF in Australia and to identify factors associated with survival. This population-based cohort study used prospectively collected data from 23 Australian CF centres participating in the Australian CF Data Registry (ACFDR) from 2005-2020. Period survival analysis was used to calculate median age of survival estimates for each 5-year window from 2005-2009 until 2016-2020. The overall median survival was estimated using the Kaplan-Meier method. Between 2005-2020 the ACFDR followed 4,601 people with CF, noting 516 (11.2%) deaths including 195 following lung transplantation. Out of the total sample, more than half (52.5%) were male and 395 (8.6%) had undergone lung transplantation. Two thirds of people with CF (66.1%) were diagnosed before six weeks of age or by newborn/prenatal screening. The overall median age of survival was estimated as 54.0 years (95% CI: 51.0-57.04). Estimated median survival increased from 48.9 years (95% CI: 44.7-53.5) for people with CF born in 2005-2009, to 56.3 years (95% CI: 51.2-60.4) for those born in 2016-2020. Factors independently associated with reduced survival include receiving a lung transplant, having low FEV1pp and BMI. Median survival estimates are increasing in CF in Australia. This likely reflects multiple factors, including newborn screening, improvement in diagnosis, refinements in CF management and centre-based multidisciplinary care.
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Fibrose Cística , Transplante de Pulmão , Adolescente , Feminino , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Austrália/epidemiologia , Estudos de Coortes , Fibrose Cística/epidemiologia , Fibrose Cística/cirurgia , Triagem NeonatalRESUMO
PURPOSE OF REVIEW: With improving life expectancy and quality of life, sexual and reproductive health (SRH) has become an increasingly important aspect of patient-centered cystic fibrosis care. This review aims to describe advances in cystic fibrosis-related SRH and highlight optimal practices. RECENT FINDINGS: Recent publications suggest that people with cystic fibrosis follow a similar trajectory of sexual development and activity as their noncystic fibrosis peers, although contraception use is lower. Although fertility is reduced in patients with cystic fibrosis, improved survival and assisted reproductive technologies have led to an increasing pursuit and incidence of pregnancy. Cystic fibrosis transmembrane regulator modulators that correct the underlying cystic fibrosis defect might improve fertility and thus far appear safe in pregnancy, though data are limited.Despite medical knowledge of SRH in cystic fibrosis, patients continue to report they lack sufficient education about these aspects of their healthcare, and cystic fibrosis multidisciplinary teams are ill prepared to counsel their patients. SUMMARY: Understanding of the effects of cystic fibrosis on SRH continues to improve, although many questions remain regarding optimal care from the choice of contraception to the safety of cystic fibrosis-specific medications in pregnancy. Further development of cystic fibrosis-informed interdisciplinary specialist networks and a wider framework of practice would both enhance health outcomes and better support patients.
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Fibrose Cística/terapia , Saúde Reprodutiva , Saúde Sexual , Comportamento Contraceptivo , Fibrose Cística/fisiopatologia , Feminino , Fertilidade , Humanos , Masculino , Assistência Centrada no Paciente , Gravidez , Qualidade de Vida , Saúde Reprodutiva/educação , Comportamento Sexual , Saúde Sexual/educaçãoRESUMO
BACKGROUND: Both infection and inflammation are critical to the progression of cystic fibrosis (CF) lung disease. Potential anatomical differences in lower airway infection, inflammation and bronchiectasis in young children with CF raise questions regarding the pathogenesis of early structural lung disease. METHODS: A longitudinal multi-centre birth cohort study of infants newly diagnosed with CF was conducted. Paired bronchoalveolar lavage (BAL) samples were obtained from the right middle lobe (RML) and lingula bronchi. Chest computed tomography (CT) was performed biennially and analysed using the modified CF-CT scoring system. RESULTS: One hundred and twenty-four children (0.11 - 7.0 years) contributed 527 BAL samples and underwent 388 CT chest scans. Pro-inflammatory microbes were detected in 279 BAL samples (53%), either in both lingula and RML samples (69%), in the lingula alone (24%), or in the RML alone in only 7% of samples. Overall, the prevalence of structural lung disease was greater in the setting of pro-inflammatory microbes. Although infection was less commonly isolated in the right lung, bronchiectasis was more commonly detected in the right lung compared with the left. No anatomical differences in the presence of air trapping were detected. CONCLUSION: Overall, the detection of pro-inflammatory microbes in the lower airways was associated with increased risk of both air trapping and bronchiectasis. However, the apparent discordance between commonest sites of isolation of pro-inflammatory microbes and the anatomical site of early bronchiectasis warrants further exploration.
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Bronquiectasia/microbiologia , Fibrose Cística/fisiopatologia , Infecções Respiratórias/complicações , Lavagem Broncoalveolar , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Lactente , Recém-Nascido , Inflamação/microbiologia , Estudos Longitudinais , Masculino , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Cystic fibrosis (CF) lung disease commences in infancy, and understanding the role of the microbiota in disease pathogenesis is critical. This study examined and compared the lower airway microbiota of infants with and without CF and its relationship to airway inflammation in the first months of life. METHODS: Infants newly-diagnosed with CF were recruited into a single-centre study in Melbourne, Australia from 1992 to 2001. Bronchoalveolar lavage was performed at study entry. Healthy infants undergoing bronchoscopy to investigate chronic stridor acted as controls. Quantitative microbiological culture was performed and inflammatory markers were measured contemporaneously. 16S ribosomal RNA gene analysis was performed on stored samples. RESULTS: Thirteen bronchoalveolar samples from infants with CF and nine from control infants, collected at median ages of 1.8-months (25th-75th percentile 1.5 to 3.1-months) and 5-months (25th-75th percentile 2.9 to 8.2-months) respectively, provided 16S rRNA gene data. Bacterial biomass was positively associated with inflammation. Alpha diversity was reduced in infants with CF and between-group compositional differences were apparent. These differences were driven by increased Staphylococcus and decreased Fusobacterium and were most apparent in symptomatic infants with CF. CONCLUSION: In CF lung disease, differences in lower airway microbial community composition and structure are established by age 6-months.
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Fibrose Cística/microbiologia , Pulmão/microbiologia , Microbiota , Austrália , Líquido da Lavagem Broncoalveolar , Broncoscopia , Estudos de Casos e Controles , Feminino , Humanos , Lactente , Masculino , RNA Ribossômico 16SRESUMO
This systematic review synthesizes published articles investigating the prevalence, severity and impact of urinary incontinence (UI), a condition associated with cystic fibrosis (CF). References were identified through searching Medline, Embase and PubMed using the medical subject headings 'cystic fibrosis' AND 'urinary incontinence'. Articles were included if UI prevalence was investigated as an outcome. Twelve studies met selection criteria. The prevalence of UI ranged from 5% to 76%. Age and gender contributed to this variability. When assessed, UI commonly limited airway clearance, exercise and/or spirometry, and had a variable impact on patients' lives. Worry and embarrassment were features for many; others were less affected. In CF, UI is common and can interfere with respiratory care and social well-being. The prevalence, characteristics and impact are poorly understood, which is made worse by inconsistent definitions across studies. Future research is needed to improve approaches to prevention, identification, management and education.
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Fibrose Cística/complicações , Incontinência Urinária/epidemiologia , Incontinência Urinária/etiologia , Fatores Etários , Ansiedade/etiologia , Exercício Físico , Humanos , Prevalência , Fatores Sexuais , Vergonha , Espirometria , Incontinência Urinária/psicologiaRESUMO
Infection plays a critical role in the pathogenesis of cystic fibrosis (CF) lung disease. Over the past two decades, the application of molecular and extended culture-based techniques to microbial analysis has changed our understanding of the lungs in both health and disease. CF lung disease is a polymicrobial disorder, with obligate and facultative anaerobes recovered alongside traditional pathogens in varying proportions, with some differences observed to correlate with disease stage. While healthy lungs are not sterile, differences between the lower airway microbiota of individuals with CF and disease-controls are already apparent in childhood. Understanding the evolution of the CF airway microbiota, and its relationship with clinical treatments and outcome at each disease stage, will improve our understanding of the pathogenesis of CF lung disease and potentially inform clinical management. This review summarizes current knowledge of the early development of the respiratory microbiota in healthy children and then discusses what is known about the airway microbiota in individuals with CF, including how it evolves over time and where future research priorities lie.
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Fibrose Cística/microbiologia , Microbiota , Sistema Respiratório/microbiologia , HumanosRESUMO
RATIONALE: The underlying defect in the cystic fibrosis (CF) airway leads to defective mucociliary clearance and impaired bacterial killing, resulting in endobronchial infection and inflammation that contributes to progressive lung disease. Little is known about the respiratory microbiota in the early CF airway and its relationship to inflammation. OBJECTIVES: To examine the bacterial microbiota and inflammatory profiles in bronchoalveolar lavage fluid and oropharyngeal secretions in infants with CF. METHODS: Infants with CF from U.S. and Australian centers were enrolled in a prospective, observational study examining the bacterial microbiota and inflammatory profiles of the respiratory tract. Bacterial diversity and density (load) were measured. Lavage samples were analyzed for inflammatory markers (interleukin 8, unbound neutrophil elastase, and absolute neutrophil count) in the epithelial lining fluid. RESULTS: Thirty-two infants (mean age, 4.7 months) underwent bronchoalveolar lavage and oropharyngeal sampling. Shannon diversity strongly correlated between upper and lower airway samples from a given subject, although community compositions differed. Microbial diversity was lower in younger subjects and in those receiving daily antistaphylococcal antibiotic prophylaxis. In lavage samples, reduced diversity correlated with lower interleukin 8 concentration and absolute neutrophil count. CONCLUSIONS: In infants with CF, reduced bacterial diversity in the upper and lower airways was strongly associated with the use of prophylactic antibiotics and younger age at the time of sampling; less diversity in the lower airway correlated with lower inflammation on bronchoalveolar lavage. Our findings suggest modification of the respiratory microbiome in infants with CF may influence airway inflammation.
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Antibioticoprofilaxia , Fibrose Cística/complicações , Microbiota , Sistema Respiratório/microbiologia , Austrália , Bactérias/isolamento & purificação , Biomarcadores/metabolismo , Líquido da Lavagem Broncoalveolar/microbiologia , Fibrose Cística/microbiologia , Feminino , Humanos , Lactente , Inflamação , Interleucina-8/metabolismo , Contagem de Leucócitos , Elastase de Leucócito/metabolismo , Modelos Lineares , Masculino , Missouri , Neutrófilos/metabolismo , Estudos ProspectivosRESUMO
RATIONALE: In infants and young children with cystic fibrosis, lower airway infection and inflammation are associated with adverse respiratory outcomes. However, the role of lower airway microbiota in the pathogenesis of early cystic fibrosis lung disease remains uncertain. OBJECTIVES: To assess the development of the lower airway microbiota over time in infants and young children with cystic fibrosis, and to explore its association with airway inflammation and pulmonary function at age 6â years. METHODS: Serial, semi-annual bronchoscopies and bronchoalveolar lavage (BAL) procedures were performed in infants newly diagnosed with cystic fibrosis following newborn screening. Quantitative microbiological cultures and inflammatory marker (interleukin 8 and neutrophil elastase) measurements were undertaken contemporaneously. 16S ribosomal RNA gene sequencing was conducted on stored BAL samples. Spirometry results recorded at 6â years of age were extracted from medical records. MEASUREMENTS AND MAIN RESULTS: Ninety-five BAL samples provided 16S ribosomal RNA gene data. These were collected from 48 subjects aged 1.2-78.3â months, including longitudinal samples from 27 subjects and 13 before age 6â months. The lower airway microbiota varied, but diversity decreased with advancing age. Detection of recognised cystic fibrosis bacterial pathogens was associated with reduced microbial diversity and greater lower airway inflammation. There was no association between the lower airway microbiota and pulmonary function at age 6â years. CONCLUSIONS: In infants with cystic fibrosis, the lower airway microbiota is dynamic. Dominance of the microbiota by recognised cystic fibrosis bacterial pathogens is associated with increased lower airway inflammation, however early microbial diversity is not associated with pulmonary function at 6â years of age.
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Infecções Bacterianas/microbiologia , Fibrose Cística/microbiologia , Microbiota , Infecções Respiratórias/microbiologia , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/fisiopatologia , Técnicas de Tipagem Bacteriana/métodos , Biomarcadores/sangue , Líquido da Lavagem Broncoalveolar/microbiologia , Broncoscopia , Fibrose Cística/tratamento farmacológico , Fibrose Cística/fisiopatologia , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Lactente , Recém-Nascido , Mediadores da Inflamação/sangue , Estudos Longitudinais , Pulmão/microbiologia , Masculino , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/fisiopatologia , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/fisiopatologia , Capacidade Vital/fisiologiaRESUMO
Adolescents and adults with cystic fibrosis now approach developmental milestones, including sexual and reproductive ones, at a similar time to their healthy peers. Yet, their sexual and reproductive health (SRH) is profoundly affected by their disease, and their SRH decisions can substantially affect their health. Navigation of SRH milestones in the context of cystic fibrosis needs education, guidance, and access to SRH services. In this Review, we discuss scientific knowledge of SRH in patients with cystic fibrosis across the life course and clinical practices for SRH within cystic fibrosis care. We identify crucial gaps in SRH education of patients and their access to resources and then present a model of care for provision of developmentally appropriate SRH education and care within cystic fibrosis services across the life course. This model emphasises the central importance of the cystic fibrosis team and service links to primary and specialist SRH care.
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Fibrose Cística/complicações , Serviços de Saúde Reprodutiva , Saúde Reprodutiva , Comportamento Sexual , Adolescente , Adulto , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Adulto JovemRESUMO
OBJECTIVE: Improved life expectancy in cystic fibrosis (CF) alters the significance of developmentally relevant aspects such as sexual and reproductive health (SRH). Men with CF report parents are an important source of information about infertility, but parent perspectives remain unknown. The aim of this study was to systematically explore parents' knowledge, attitudes and behaviors regarding the SRH education of their sons. PATIENTS AND METHODS: Eligible participants were parents of boys with CF aged at least 6 years who completed a 61-item written questionnaire that was developed to measure parent knowledge and education about CF-specific aspects of SRH, and parent attitudes and behaviors about the CF-specific sexuality education of their sons. RESULTS: Eighty-four mothers (82%) and 64 fathers (70%) completed the questionnaire. All but one knew of probable infertility, being primarily informed at the time of diagnosis. Since then, 19% of parents reported subsequent discussions of SRH with their son's CF specialist, mostly initiated by parents. Adolescence was considered the most appropriate time for the initial education of boys. Sixty percent of parents worried how their sons would react. Ninety-five percent of parents said that they (alone or together with the CF specialist) should first inform their sons of probable infertility. Only 30% of parents were satisfied with their current knowledge. CONCLUSION: These parents are well informed about male infertility in CF. However, they have had little opportunity for subsequent discussion of SRH with health professionals since their son's diagnosis. As boys mature, subsequent SRH discussions by health professionals with parents are indicated.