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Rationale: Conventionally considered irreversible, bronchiectasis has been demonstrated to be reversible in children in small studies. However, the factors associated with radiographic reversibility of bronchiectasis have yet to be defined. Objectives: In a large cohort of children with bronchiectasis, we aimed to determine: 1) if and to what extent bronchiectasis is reversible and 2) factors associated with radiographic chest high-resolution computed tomography (cHRCT) resolution. Methods: We identified children with bronchiectasis who had a repeat multidetector cHRCT scan between 2010 and 2021. We excluded those with cystic fibrosis, surgical pulmonary resection, traction bronchiectasis only, or lobar opacification. Measurements and Main Results: cHRCT scans were scored using the modified Reiff score (MRS) with a pediatric correction. Resolution was defined as an absence of abnormal bronchoarterial ratio (>0.8) on the second cHRCT scan. We included 142 children (median age, 5 years; IQR, 2.6-7.4). Inter- and intrarater agreement in MRSs was excellent (weighted κ = 0.83-0.86 and 0.95, respectively). There was radiographic resolution in 57 of 142 patients (40.1%), improvement in 56 of 142 (39.4%), and no change or worsening in 29 of 142 (20.4%). Pseudomonas aeruginosa (PsA) was absolutely associated with a lack of resolution. On multivariable regression, in those without PsA cultured, younger age at the time of diagnosis (risk ratio [RR], 0.94; 95% confidence interval [CI], 0.88-0.99), lower MRS (RR, 0.89; 95% CI, 0.82-0.97), and lower annual rate of exacerbations requiring intravenous antibiotic therapy (RR, 0.60; 95% CI, 0.37-0.98) increased the likelihood of radiographic resolution. Conclusions: This first large cohort confirms that bronchiectasis in children is often reversible with appropriate management. Younger children and those with lesser radiographic severity at diagnosis were most likely to exhibit radiographic reversibility, whereas those with PsA infection were least likely.
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Bronquiectasia , Humanos , Bronquiectasia/diagnóstico por imagem , Masculino , Feminino , Criança , Pré-Escolar , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Estudos de Coortes , Tomografia Computadorizada Multidetectores/métodosRESUMO
BACKGROUND: ICU outcomes are continuing to improve. However, this has not been matched by similar improvements of the ICU bedspace environment, which can detrimentally impact on patient outcomes. Excessive sound and noise, especially, has been linked with adverse and potentially preventable patient outcomes and staff errors. There are many sources of sound in the ICU, with alarms from bedside equipment frequently listed as a main source. The number of alarms is increasing in parallel with the introduction of new and more sophisticated technologies to monitor and support patients. However, most alarms are not accurate or critical and are commonly ignored by staff. OBJECTIVE: The objective of this study was to evaluate the impact of a sound reduction bundle on sound levels, number of alarms, and patients' experience and perceived quality of sleep in the ICU. METHODS: This was a pre-post, quasi-experimental study investigating the impact of three study interventions implemented sequentially (staff education, visual warnings when sound levels exceeded the preset levels, and monitor alarm reconfigurations). Effects of staff education were evaluated using pre-education and post-education questionnaires, and the impact on patients was evaluated via self-report questionnaires. A sound-level monitor was used to evaluate changes in sound levels between interventions. Alarm audits were completed before and after alarm reconfiguration. RESULTS: Staff knowledge improved; however, sound levels did not change across interventions. The number of monthly monitor alarms reduced from 600,452 to 115,927. No significant differences were found in patients' subjective rating of their experience and sleep. CONCLUSION: The interventions did not lead to a sound-level reduction; however, there was a large reduction in ICU monitor alarms without any alarm-related adverse events. As the sources of sound are diverse, multidimensional interventions, including staff education, alarm management solutions, and environmental redesign, are likely to be required to achieve a relevant, lasting, and significant sound reduction.
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Alarmes Clínicos , Unidades de Terapia Intensiva , Ruído , Humanos , Masculino , Feminino , Inquéritos e Questionários , Pessoa de Meia-Idade , AdultoRESUMO
BACKGROUND: ICU survival is improving. However, many patients leave ICU with ongoing cognitive, physical, and/or psychological impairments and reduced quality of life. Many of the reasons for these ongoing problems are unmodifiable; however, some are linked with the ICU environment. Suboptimal lighting and excessive noise contribute to a loss of circadian rhythms and sleep disruptions, leading to increased mortality and morbidity. Despite long-standing awareness of these problems, meaningful ICU redesign is yet to be realised, and the 'ideal' ICU design is likely to be unique to local context and patient cohorts. To inform the co-design of an improved ICU environment, this study completed a detailed evaluation of the ICU environment, focussing on acoustics, sound, and light. METHODS: This was an observational study of the lighting and acoustic environment using sensors and formal evaluations. Selected bedspaces, chosen to represent different types of bedspaces in the ICU, were monitored during prolonged study periods. Data were analysed descriptively using Microsoft Excel. RESULTS: Two of the three monitored bedspaces showed a limited difference in lighting levels across the day, with average daytime light intensity not exceeding 300 Lux. In bedspaces with a window, the spectral power distribution (but not intensity) of the light was similar to natural light when all ceiling lights were off. However, when the ceiling lights were on, the spectral power distribution was similar between bedspaces with and without windows. Average sound levels in the study bedspaces were 63.75, 56.80, and 59.71 dBA, with the single room being noisier than the two open-plan bedspaces. There were multiple occasions of peak sound levels > 80 dBA recorded, with the maximum sound level recorded being > 105 dBA. We recorded one new monitor or ventilator alarm commencing every 69 s in each bedspace, with only 5% of alarms actioned. Acoustic testing showed poor sound absorption and blocking. CONCLUSIONS: This study corroborates other studies confirming that the lighting and acoustic environments in the study ICU were suboptimal, potentially contributing to adverse patient outcomes. This manuscript discusses potential solutions to identified problems. Future studies are required to evaluate whether an optimised ICU environment positively impacts patient outcomes.
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Unidades de Terapia Intensiva , Qualidade de Vida , Humanos , Ruído/efeitos adversos , Iluminação , LuzRESUMO
Idiopathic pulmonary fibrosis (IPF) is the most common and lethal form of the interstitial pneumonias. The cause of the disease is unknown, and new therapies that stop or reverse disease progression are desperately needed. Recent advances in next-generation sequencing have led to an abundance of freely available, clinically relevant, organ-and-disease-specific, single-cell transcriptomic data, including studies from patients with IPF. We mined data from published IPF data sets and identified gene signatures delineating pro-fibrotic or antifibrotic macrophages and then used the Enrichr platform to identify compounds with the potential to drive the macrophages toward the antifibrotic transcriptotype. We then began testing these compounds in a novel in vitro phenotypic drug screening assay utilising human lung macrophages recovered from whole-lung lavage of patients with silicosis. As predicted by the Enrichr tool, glitazones potently modulated macrophage gene expression towards the antifibrotic phenotype. Next, we assayed a subset of the NatureBank pure compound library and identified the cyclobutane lignan, endiandrin A, which was isolated from the roots of the endemic Australian rainforest plant, Endiandra anthropophagorum, with a similar antifibrotic potential to the glitazones. These methods open new avenues of exploration to find treatments for lung fibrosis.
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Fibrose Pulmonar Idiopática , Tiazolidinedionas , Humanos , Austrália , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/metabolismo , Pulmão/metabolismo , Macrófagos/metabolismo , Tiazolidinedionas/uso terapêuticoRESUMO
Bronchiectasis is being diagnosed increasingly in children and adolescents. Recurrent respiratory exacerbations are common in children and adolescents with this chronic pulmonary disorder. Respiratory exacerbations are associated with an impaired quality of life, poorer long-term clinical outcomes, and substantial costs to the family and health systems. The 2021 European Respiratory Society (ERS) clinical practice guideline for the management of children and adolescents with bronchiectasis provided a definition of acute respiratory exacerbations for clinical use but to date there is no comparable universal definition for clinical research. Given the importance of exacerbations in the field, this ERS Task Force sought to obtain robust definitions of respiratory exacerbations for clinical research. The panel was a multidisciplinary team of specialists in paediatric and adult respiratory medicine, infectious disease, physiotherapy, primary care, nursing, radiology, methodology, patient advocacy, and parents of children and adolescents with bronchiectasis. We used a standardised process that included a systematic literature review, parent survey, and a Delphi approach involving 299 physicians (54 countries) caring for children and adolescents with bronchiectasis. Consensus was obtained for all four statements drafted by the panel as the disagreement rate was very low (range 3.6-7.2%). The panel unanimously endorsed the four consensus definitions for 1a) non-severe exacerbation and 1b) severe exacerbation as an outcome measure, 2) non-severe exacerbation for studies initiating treatment, and 3) resolution of a non-severe exacerbation for clinical trials involving children and adolescents with bronchiectasis. This ERS Task Force proposes using these internationally derived, consensus-based definitions of respiratory exacerbations for future clinical paediatric bronchiectasis research.
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Antibacterianos , Bronquiectasia , Adulto , Adolescente , Criança , Humanos , Antibacterianos/uso terapêutico , Qualidade de Vida , Bronquiectasia/terapia , Bronquiectasia/tratamento farmacológico , Sistema Respiratório , Avaliação de Resultados em Cuidados de SaúdeRESUMO
A systematic electronic search of MEDLINE, EMBASE, and CINAHL databases aimed at comparing neurokinin-1 receptor antagonists with other antiemetics in their prevention of postoperative nausea and vomiting in adult patients undergoing laparoscopic surgery identified seven randomized controlled trials for review and meta-analysis. Preoperative aprepitant 80 mg was found to reduce nausea (RR: 0.56, 95% CI: 0.41-0.75, I2 = 0%, P = 0.89) and vomiting (RR: 0.20, 95% CI: 0.05-0.77, I2 = 0%, P = 0.96) and resulted in complete response (RR: 1.61 (1.25-2.08), I2 = 0%, P = 0.70) within the first 2 hours following surgery as well as vomiting in 2-24 hours (RR: 0.09, 95% CI: 0.02-0.36, I2 = 0%; P = 0.81) when compared to placebo or no antiemetic therapy. Preoperative aprepitant 80 mg has a superior overall effect compared to placebo or other antiemetics in the first two hours postoperatively, and thereafter reduces the risk of vomiting alone in the first 24 hours following laparoscopic surgeries.
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BACKGROUND AND OBJECTIVE: Long-term data on children with PBB has been identified as a research priority. We describe the 5-year outcomes for children with PBB to ascertain the presence of chronic respiratory disease (bronchiectasis, recurrent PBB and asthma) and identify the risk factors for these. METHODS: Prospective cohort study was undertaken at the Queensland Children's Hospital, Brisbane, Australia, of 166 children with PBB and 28 controls (undergoing bronchoscopy for symptoms other than chronic wet cough). Monitoring was by monthly contact via research staff. Clinical review, spirometry and CT chest were performed as clinically indicated. RESULTS: A total of 194 children were included in the analysis. Median duration of follow-up was 59 months (IQR: 50-71 months) post-index PBB episode, 67.5% had ongoing symptoms and 9.6% had bronchiectasis. Significant predictors of bronchiectasis were recurrent PBB in year 1 of follow-up (ORadj = 9.6, 95% CI: 1.8-50.1) and the presence of Haemophilus influenzae in the BAL (ORadj = 5.1, 95% CI: 1.4-19.1). Clinician-diagnosed asthma at final follow-up was present in 27.1% of children with PBB. A significant BDR (FEV1 improvement >12%) was obtained in 63.5% of the children who underwent reversibility testing. Positive allergen-specific IgE (ORadj = 14.8, 95% CI: 2.2-100.8) at baseline and bronchomalacia (ORadj = 5.9, 95% CI: 1.2-29.7) were significant predictors of asthma diagnosis. Spirometry parameters were in the normal range. CONCLUSION: As a significant proportion of children with PBB have ongoing symptoms at 5 years, and outcomes include bronchiectasis and asthma, they should be carefully followed up clinically. Defining biomarkers, endotypes and mechanistic studies elucidating the different outcomes are now required.
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Infecções Bacterianas , Bronquiectasia , Bronquite Crônica , Bronquite , Tosse/fisiopatologia , Bronquiectasia/epidemiologia , Bronquite/diagnóstico , Bronquite/epidemiologia , Criança , Humanos , Estudos ProspectivosRESUMO
Viral respiratory infections are usually benign but can trigger asthma exacerbations. The factors associated with upper respiratory tract infection (cold) frequency are not fully understood, nor is it clear whether such factors differ between women and men.To determine which immunological and clinical variables associate with the frequency of self-reported respiratory infections (colds), 150 asthma cases and 151 controls were recruited. Associations between antiviral immune response variables: toll-like receptor (TLR)7/8 gene expression, plasmacytoid dendritic cell (pDC) numbers and interferon-α, tumour necrosis factor and interleukin-12 production, and asthma were then examined that might explain cold frequency.People with asthma cases reported more colds per year (median 3 versus 2; p<0.001) and had lower baseline TLR7 gene expression (odds ratio 0.12; p=0.02) than controls. Associations between many variables and cold frequency differed between women and men. In women, high blood neutrophil counts (ß=0.096, p=0.002), and younger age (ß=-0.017, p<0.001), but not exposure to children, were independently associated with more frequent colds. In men, low TLR7 expression (ß=-0.96, p=0.041) and high CLEC4C gene expression (a marker of pDC; ß=0.88, p=0.008) were independently associated with more frequent colds. Poor asthma symptom control was independently associated with reduced TLR8 gene expression (ß=-1.4, p=0.036) and high body mass index (ß=0.041, p=0.004).Asthma, age and markers of inflammation and antiviral immunity in peripheral blood are associated with frequent colds. Interestingly, the variables associated with cold frequency differed between women and men.
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Asma , Infecções Respiratórias , Criança , Células Dendríticas , Feminino , Humanos , Lectinas Tipo C , Leucócitos , Masculino , Glicoproteínas de Membrana , Receptores Imunológicos , Receptor 7 Toll-Like/genéticaAssuntos
Bronquiectasia , Adolescente , Bronquiectasia/terapia , Consenso , Família , Humanos , Padrões de ReferênciaRESUMO
BACKGROUND AND OBJECTIVE: In cystic fibrosis (CF), chronic Pseudomonas aeruginosa infection is associated with increased morbidity, antibiotic treatments and mortality. By linking Australian CF registry data with a national microbiological data set, we examined the association between where treatment was delivered, its intensity and P. aeruginosa antibiotic resistance. METHODS: Sputa were collected from paediatric and adult CF patients attending 18 Australian CF centres. P. aeruginosa antibiotic susceptibilities determined by local laboratories were correlated with clinical characteristics, treatment intensity and infection with strains commonly shared among Australian CF patients. Between-centre differences in treatment and antibiotic resistance were also compared. RESULTS: Large variations in antibiotic usage, maintenance treatment practices and multi-antibiotic resistant P. aeruginosa (MARPA) prevalence exist between Australian CF centres, although the overall proportions of MARPA isolates were similar in paediatric and adult centres (31% vs 35%, P = 0.29). Among paediatric centres, MARPA correlated with intravenous antibiotic usage and the Australian state where treatment was delivered, while azithromycin, reduced lung function and treating state predicted intravenous antibiotic usage. In adult centres, body mass index (BMI) and treating state were associated with MARPA, while intravenous antibiotic use was predicted by gender, BMI, dornase-alpha, azithromycin, lung function and treating state. In adults, P. aeruginosa strains AUST-01 and AUST-02 independently predicted intravenous antibiotic usage. CONCLUSION: Increased treatment intensity in paediatric centres and the Australian state where treatment was received are both associated with greater risk of MARPA, but not worse clinical outcomes.
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Antibacterianos/uso terapêutico , Fibrose Cística/complicações , Farmacorresistência Bacteriana Múltipla , Instalações de Saúde , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Administração Intravenosa , Adulto , Antibacterianos/administração & dosagem , Austrália , Azitromicina/uso terapêutico , Índice de Massa Corporal , Criança , Fibrose Cística/fisiopatologia , Uso de Medicamentos , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Padrões de Prática Médica , Sistema de Registros , Testes de Função Respiratória , Fatores Sexuais , Escarro/microbiologiaRESUMO
BACKGROUND: Chronic neutrophilic inflammation, in both the presence and absence of infection, is a feature of bronchiectasis in adults and children. The anti-inflammatory properties of non-steroid anti-inflammatory drugs (NSAIDs) may be beneficial in reducing airway inflammation, thus potentially improving lung function and quality of life in patients with bronchiectasis. OBJECTIVES: To evaluate the efficacy of inhaled NSAIDs in the management of non-cystic fibrosis bronchiectasis in children and adults:⢠during stable bronchiectasis; and⢠for reduction of:∘ severity and frequency of acute respiratory exacerbations; and∘ long-term pulmonary decline. SEARCH METHODS: We searched the Cochrane Airways Group Trials Register, which includes reports identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We also searched the trial registry ClinicalTrials.gov and the World Health Organization (WHO) trial portal. We carried out the latest searches on 22 September 2015. SELECTION CRITERIA: All randomised controlled trials comparing inhaled NSAIDs versus a control (placebo or usual treatment) in children or adults with bronchiectasis not related to cystic fibrosis. DATA COLLECTION AND ANALYSIS: We reviewed the results of searches against predetermined criteria for inclusion. MAIN RESULTS: One small, short-term trial was eligible for inclusion. We included this study of 25 adults with chronic lung disease (only 32% of people included in the trial had bronchiectasis), as the other conditions were linked to development of bronchiectasis, and all were characterised by chronic sputum production. We were not able to obtain separate data for people with a diagnosis of bronchiectasis. We judged that the study was at a high risk of selection bias.The primary outcome (mean difference in control of bronchiectasis severity, quality of life (Qol), cough scores) was not reported in the included study. The single trial in adults reported a significant reduction in sputum production over 14 days for the treatment group (inhaled indomethacin) compared with the placebo group (mean difference (MD) -75.00 g/day; 95% confidence interval (CI) -134.61 to -15.39) and a significant improvement in the Borg Dyspnoea Scale score (MD -1.90, 95% CI -3.15 to -0.65). We noted no significant differences between groups in lung function or blood indices and no reported adverse events. AUTHORS' CONCLUSIONS: No new studies of adults or children have been conducted since the last version of this review was published. Therefore, final conclusions have not changed. Current evidence is insufficient to support or refute the use of inhaled NSAIDs for the management of bronchiectasis in adults or children. One small trial reported a reduction in sputum production and improved dyspnoea among adults with chronic lung disease who were treated with inhaled indomethacin, indicating that additional studies on the efficacy of NSAIDs for treatment of patients with bronchiectasis are warranted.
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Anti-Inflamatórios não Esteroides/administração & dosagem , Bronquiectasia/tratamento farmacológico , Administração por Inalação , Adulto , Criança , Dispneia/tratamento farmacológico , Humanos , Escarro/metabolismoRESUMO
BACKGROUND: People with cystic fibrosis (CF) may work in healthcare settings risking nosocomial pathogen acquisition. The aim of this study was to determine the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection in adult healthcare workers with CF (HCWcf). METHODS: Data was collected in this observational study on MRSA acquisition from 405 CF patients attending an adult CF centre in Australia between 2001-2012. Demographic and clinical characteristics were compared between HCWcf and non-HCWcf. A sub-analysis was subsequently performed to compare demographic and clinical characteristics between those patients (HCWcf versus non-HCWcf) that acquired MRSA. We also investigated rates of chronic MRSA infection and the outcome of eradication treatment in HCWcf. RESULTS: A higher proportion of HCWcf acquired MRSA [n = 10/21] compared to non-HCWcf [n = 40/255] (P <0.001). The odds of MRSA acquisition were 8.4 (95 % CI, 3.0 - 23.4) times greater in HCWcf than non-HCWcf. HCWcf with MRSA were older (P = 0.02) and had better lung function (P = 0.009), yet hospitalisation rates were similar compared to non-HCWcf with MRSA. Chronic MRSA infection developed in 36/50 CF patients (HCWcf, n = 6; non-HCWcf, n = 30), with eradication therapy achieved in 5/6 (83 %) HCWcf. CONCLUSIONS: The rate of MRSA incidence was highest in HCWcf and the workplace is a possible source of acquisition. Vocational guidance should include the potential for MRSA acquisition for CF patients considering healthcare professions.
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Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Fibrose Cística/complicações , Pessoal de Saúde , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Adulto , Antibacterianos/uso terapêutico , Austrália , Estudos Transversais , Feminino , Ácido Fusídico/uso terapêutico , Humanos , Incidência , Linezolida/uso terapêutico , Modelos Logísticos , Masculino , Análise Multivariada , Estudos Retrospectivos , Rifampina/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The role of human adenoviruses (HAdVs) in chronic respiratory disease pathogenesis is recognized. However, no studies have performed molecular sequencing of HAdVs from the lower airways of children with chronic endobronchial suppuration. We thus examined the major HAdV genotypes/species, and relationships to bacterial coinfection, in children with protracted bacterial bronchitis (PBB) and mild bronchiectasis (BE). METHODS: Bronchoalveolar lavage (BAL) samples of 245 children with PBB or mild (cylindrical) BE were included in this prospective cohort study. HAdVs were genotyped (when possible) in those whose BAL had HAdV detected (HAdV(+)). Presence of bacterial infection (defined as ≥10(4) colony-forming units/mL) was compared between BAL HAdV(+) and HAdV negative (HAdV(-)) groups. Immune function tests were performed including blood lymphocyte subsets in a random subgroup. RESULTS: Species C HAdVs were identified in 23 of 24 (96%) HAdV(+) children; 13 (57%) were HAdV-1 and 10 (43%) were HAdV-2. An HAdV(+) BAL was significantly associated with bacterial coinfection with Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae (odds ratio [OR], 3.27; 95% confidence interval, 1.38-7.75; P = .007) and negatively associated with Staphylococcus aureus infection (P = .03). Young age was related to increased rates of HAdV(+). Blood CD16 and CD56 natural killer cells were significantly more likely to be elevated in those with HAdV (80%) compared with those without (56.1%) (P = .027). CONCLUSIONS: HAdV-C is the major HAdV species detected in the lower airways of children with PBB and BE. Younger age appears to be an important risk factor for HAdV(+) of the lower airways and influences the likelihood of bacterial coinfection.
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Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/classificação , Bronquiolite Viral/virologia , Infecções por Adenovirus Humanos/epidemiologia , Adenovírus Humanos/genética , Adenovírus Humanos/isolamento & purificação , Bronquiolite Viral/epidemiologia , Líquido da Lavagem Broncoalveolar/virologia , Criança , Pré-Escolar , Doença Crônica , Estudos de Coortes , Feminino , Técnicas de Genotipagem , Humanos , Lactente , Estudos Longitudinais , Masculino , Estudos ProspectivosRESUMO
BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a degenerative disease characterized by fibrosis following failed epithelial repair. Mesenchymal stromal cells (MSC), a key component of the stem cell niche in bone marrow and possibly other organs including lung, have been shown to enhance epithelial repair and are effective in preclinical models of inflammation-induced pulmonary fibrosis, but may be profibrotic in some circumstances. METHODS: In this single centre, non-randomized, dose escalation phase 1b trial, patients with moderately severe IPF (diffusing capacity for carbon monoxide (DLCO ) ≥ 25% and forced vital capacity (FVC) ≥ 50%) received either 1 × 10(6) (n = 4) or 2 × 10(6) (n = 4) unrelated-donor, placenta-derived MSC/kg via a peripheral vein and were followed for 6 months with lung function (FVC and DLCO ), 6-min walk distance (6MWD) and computed tomography (CT) chest. RESULTS: Eight patients (4 female, aged 63.5 (57-75) years) with median (interquartile range) FVC 60 (52.5-74.5)% and DLCO 34.5 (29.5-40)% predicted were treated. Both dose schedules were well tolerated with only minor and transient acute adverse effects. MSC infusion was associated with a transient (1% (0-2%)) fall in SaO2 after 15 min, but no changes in haemodynamics. At 6 months FVC, DLCO , 6MWD and CT fibrosis score were unchanged compared with baseline. There was no evidence of worsening fibrosis. CONCLUSIONS: Intravenous MSC administration is feasible and has a good short-term safety profile in patients with moderately severe IPF.
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Fibrose Pulmonar Idiopática/terapia , Transplante de Células-Tronco Mesenquimais , Idoso , Tolerância ao Exercício , Estudos de Viabilidade , Feminino , Humanos , Fibrose Pulmonar Idiopática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Placenta/citologia , Gravidez , Capacidade de Difusão Pulmonar , Resultado do Tratamento , Capacidade VitalRESUMO
RATIONALE: Bronchiolitis obliterans syndrome (BOS) is the primary limiting factor for long-term survival after lung transplantation, and has previously been associated with microbial infections. OBJECTIVES: To cross-sectionally and longitudinally characterize microbial communities in allografts from transplant recipients with and without BOS using a culture-independent method based on high-throughput sequencing. METHODS: Allografts were sampled by bronchoalveolar lavage, and microbial communities were profiled using 16S rRNA gene amplicon pyrosequencing. Community profiles were compared using the weighted Unifrac metric and the relationship between microbial populations, BOS, and other covariates was explored using PERMANOVA and logistic regression. MEASUREMENTS AND MAIN RESULTS: Microbial communities in transplant patients fell into two main groups: those dominated by Pseudomonas or those dominated by Streptococcus and Veillonella, which seem to be mutually exclusive lung microbiomes. Aspergillus culture was also negatively correlated with the Pseudomonas-dominated group. The reestablishment of dominant populations present in patients pretransplant, notably Pseudomonas in individuals with cystic fibrosis, was negatively correlated with BOS. CONCLUSIONS: Recolonization of the allograft by Pseudomonas in individuals with cystic fibrosis is not associated with BOS. In general, reestablishment of pretransplant lung populations in the allograft seems to have a protective effect against BOS, whereas de novo acquisition of microbial populations often belonging to the same genera may increase the risk of BOS.
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Bronquiolite Obliterante/epidemiologia , Bronquiolite Obliterante/microbiologia , Transplante de Pulmão/efeitos adversos , Pulmão/microbiologia , Adulto , Aspergillus fumigatus/isolamento & purificação , Bronquiolite Obliterante/prevenção & controle , Líquido da Lavagem Broncoalveolar/microbiologia , Fibrose Cística/microbiologia , DNA Bacteriano/análise , Feminino , Humanos , Masculino , Metagenoma , Pessoa de Meia-Idade , Análise de Componente Principal , Pseudomonas/isolamento & purificação , Medição de Risco , Fatores de Risco , Streptococcus/isolamento & purificação , Síndrome , Transplante Homólogo , Veillonella/isolamento & purificaçãoRESUMO
INTRODUCTION: Elective flexible bronchoscopy (FB) is now widely available and standard practice for a variety of indications in children with respiratory conditions. However, there are no randomised controlled trials (RCTs) that have examined its benefits (or otherwise).Our primary aim is to determine the impact of FB on the parent-proxy quality-of-life (QoL) scores. Our secondary aims are to determine if undertaking FB leads to (a) change in management and (b) improvement of other relevant patient-reported outcome measures (PROMs). We also quantified the benefits of elective FB (using 10-point Likert scale). We hypothesised that undertaking elective FB will contribute to accurate diagnosis and therefore appropriate treatment, which will in turn improve QoL and will be deemed to be beneficial from patient and doctor perspectives. METHODS AND ANALYSIS: Our parallel single-centre, single-blind RCT (commenced in May 2020) has a planned sample size of 114 children (aged <18 years) recruited from respiratory clinics at Queensland Children's Hospital, Brisbane, Australia. Children are randomised (1:1 concealed allocation) within two strata: age (≤2 vs >2 years) and indication for FB (chronic cough vs other indications) to either (a) early arm (intervention where FB undertaken within 2 weeks) or (b) delayed (control, FB undertaken at usual wait time). Our primary outcome is the difference between groups in their change in QoL at the T2 timepoint when the intervention group has had the FB and the control group has not. Our secondary outcomes are change in management, change in PROMs, adverse events and the Likert scales. ETHICS AND DISSEMINATION: The human research ethics committee of the Queensland Children's Hospital granted ethical clearance (HREC/20/QCHQ/62394). Our RCT is conducted in accordance with Good Clinical Practice and the Australian legislation. Results will be disseminated through conference presentations, teaching avenues, workshops, websites and publications. REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12620000610932.
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Broncoscopia , Qualidade de Vida , Humanos , Criança , Austrália , Queensland , Tosse Crônica , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUNDS: Understanding factors associated with anxiety of parents/carers of children with respiratory problems is clinically important yet there is relative paucity of data. In 106 children seen in the respiratory clinic of a pediatric hospital, we evaluated (a) the determinants for parental anxiety and (b) whether the anxiety scores correlate with quality-of-life (QoL) scores in the subset with chronic cough. METHODS: We opportunistically re-analyzed data of our main study that examined the benefits of using spirometry for pediatric respiratory consultation where parents completed an anxiety questionnaire (State-Trait Anxiety Inventory, STAI) pre- and postconsultation. A subset (children with chronic cough) also completed the parent-proxy quality-of-life (PC-QoL) tool. We computed the association between clinical characteristics and anxiety scores using multivariable regression and between the two patient-reported outcome measures using Spearman's correlation. RESULTS: The majority of parents/carers were women (n = 89, 84%). Most children (mean age = 10.9 years, SD = 3.7 years) were previously seen at the clinic (n = 67, 63.2%). In multivariate regression, parental anxiety score was significantly associated with reported presence of cough [coefficient ß = 17.31 (95% confidence interval 9.62, 25.1)] and lower forced expiratory volume in first second (FEV1 )/forced vital capacity (FVC) [-3.88 (-7.05, -0.71)] at preconsultation, but associated with cough only [coefficient ß = 12.04 (5.24, 18.84)] at postconsultation, all p < .05. STAI strongly correlated with PC-QoL scores at pre- but only modestly at postconsultation (rs = -.63 and -.39, respectively, p < .05). CONCLUSION: Parental anxiety levels of children attending respiratory clinics are influenced by the presence of cough and low FEV1 /FVC of their child and are associated with poorer QoL. These highlight the need for on-going research to reduce parental anxiety focusing on cough and lung function indices.
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Tosse , Qualidade de Vida , Criança , Humanos , Masculino , Feminino , Espirometria , Ansiedade/diagnóstico , PaisRESUMO
BACKGROUND: Clinical pharmacy quality indicators are often non-uniform and measure individual activities not linked to outcomes. AIM: To define a consensus agreed pharmaceutical care bundle and patient outcome measures across an entire state health service. METHOD: A four-round modified-Delphi approach with state Directors of Pharmacy was performed (n = 25). They were asked to rate on a 5-point Likert scale the relevance and measurability of 32 inpatient clinical pharmacy quality indicators and outcome measures. They also ranked clinical pharmacy activities in order from perceived most to least beneficial. Based upon these results, pharmaceutical care bundles consisting of multiple clinical pharmacy activities were formed, and relevance and measurability assessed. RESULTS: Response rate ranged from 40 to 60%. Twenty-six individual clinical pharmacy quality indicators reached consensus. The top ranked clinical pharmacy quality indicator was 'proportion of patients where a pharmacist documents an accurate list of medicines during admission'. There were nine pharmaceutical care bundles formed consisting between 3 and 7 activities. Only one pharmaceutical care bundle reached consensus: medication history, adverse drug reaction/allergy documentation, admission and discharge medication reconciliation, medication review, provision of medicines education and provision of a medication list on discharge. Sixteen outcome measures reached consensus. The top ranked were hospital acquired complications, readmission due to medication misadventure and unplanned readmission within 10 days. CONCLUSION: Consensus has been reached on one pharmaceutical care bundle and sixteen outcomes to monitor clinical pharmacy service delivery. The next step is to measure the extent of pharmaceutical care bundle delivery and the link to patient outcomes.
Assuntos
Serviço de Farmácia Hospitalar , Farmácia , Humanos , Indicadores de Qualidade em Assistência à Saúde , Preparações Farmacêuticas , Consenso , Técnica DelphiRESUMO
Chronic cough is a common symptom of many childhood lung conditions. Given the phenotypic heterogeneity of chronic cough, better characterization through endotyping is required to provide diagnostic certainty, precision therapies and to identify pathobiological mechanisms. This review summarizes recent endotype discoveries in airway diseases, particularly in relation to children, and describes the multi-omic approaches that are required to define endotypes. Potential biospecimens that may contribute to endotype and biomarker discoveries are also discussed. Identifying endotypes of chronic cough can likely provide personalized medicine and contribute to improved clinical outcomes for children.