Claire E Wainwright

Queensland Health

Structural and functional defects within the lungs of children with cystic fibrosis (CF) are detectable soon after birth and progress throughout preschool years often without overt clinical signs or symptoms. By school age, most children have structural changes such as bronchiectasis or gas trapping/hypoperfusion and lung function abnormalities tha...

Introduction. Mycobacterium abscessus complex (MABSC) is an environmental organism and opportunistic pathogen. MABSC pulmonary infections in people with cystic fibrosis are of growing clinical concern. Resistance data guide the use of macrolides and amikacin in MABSC pulmonary disease treatment. MABSC can acquire resistance against macrolides or am...

Rationale: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be efficacious and safe in patients aged 12 years and older with cystic fibrosis and at least one F508del-CFTR allele, but has not been evaluated in children <12 years of age. Objectives: To assess the safety, pharmacokinetics, and efficacy of ELX/TEZ/IVA in children 6 throug...

Background Antimicrobial resistance in cystic fibrosis (CF) Pseudomonas aeruginosa airway infection is complex and often attributed to chromosomal mutations. How these mutations emerge in specific strains or whether particular gene mutations are clinically informative is unclear. This study focused on oprD, which encodes an outer membrane porin ass...

A key measure of lung function in people with Cystic Fibrosis (CF) is Forced Expiratory Volume in the first second FEV1 percent predicted (FEV1pp). This study aimed to address challenges in identifying predictors of FEV1pp, specifically dealing with non-linearity and the censoring effect of death. Data was obtained from a large multi-centre Austral...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background Cystic fibrosis (CF) is characterised by reduced airway clearance, microbial accumulation, inflammation, and lung function decline. Certain bacterial species may contribute disproportionately to worsening lung disease. However, the relative importance of these microorganisms compared to the absolute abundance of all bacteria is uncertain...

Cystic fibrosis (CF) is a common life‐limiting genetic condition. As the disease progresses access to specialist tertiary multi‐disciplinary care services may become necessary. For patients living in regional/remote Australia, accessing such services may be a challenge. Here, we describe long‐term outcomes for CF patients according to their access...

Introduction Little is known about early predictors of later cystic fibrosis (CF) structural lung disease. This study examined early predictors of progressive structural lung abnormalities in children who completed the Australasian CF Bronchoalveolar Lavage (ACFBAL) clinical trial at age 5-years and participated in an observational follow-up study...

Defective OprD porins contribute to carbapenem resistance and may be important in Pseudomonas aeruginosa adaptation to cystic fibrosis airways. It is unclear whether oprD mutations are fixed in populations of shared strains that are transmitted between patients or whether novel variants arise during infection. We investigated oprD sequences and ant...

Background While Aspergillus detection rates in adults, adolescents and older children with cystic fibrosis (CF) have increased, the risk of acquiring this fungal pathogen in young children is unknown. Aim To determine the risk and explanatory factors of acquiring Aspergillus in children with CF by age 5 years. Methods Cross-sectional analysis of...

Respiratory disease is a major cause of morbidity and mortality in patients with ataxia-telangiectasia (A-T) who are prone to recurrent sinopulmonary infections, bronchiectasis, pulmonary fibrosis, and pulmonary failure. Upper airway infections are common in patients and S. pneumoniae is associated with these infections. We demonstrate here that th...

Background: Mycobacterium abscessus complex pulmonary disease (M. abscessus PD) in cystic fibrosis (CF) is challenging to treat. Current guideline therapeutic regimens involving an intensive phase of intravenous (IV) antibiotics followed by a consolidation phase of inhaled and oral antibiotics are not evidence-based. The objectives of this study w...

Background The impact of Aspergillus on lung disease in young children with cystic fibrosis is uncertain. Aims To determine if positive respiratory cultures of Aspergillus species are associated with: (1) increased structural lung injury at age 5 years; (2) accelerated lung function decline between ages 5 years and 14 years and (3) to identify exp...

Background and objective: Genetic modifiers contribute to variable disease phenotype in cystic fibrosis (CF). We explored the association between mutations in the hemochromatosis (HFE) gene and disease severity in adults with CF. Methods: HFE genotyping was performed in 163 adults with CF attending a single centre. Results were correlated with l...

The lungs of individuals with cystic fibrosis (CF) become chronically infected with Pseudomonas aeruginosa that is difficult to eradicate by antibiotic treatment. Two key P. aeruginosa antibiotic resistance mechanisms are the AmpC β-lactamase that degrades β-lactam antibiotics and MexXYOprM, a three-protein efflux pump that expels aminoglycoside an...

Introduction: We previously reported defective alternative polarization (M2) of macrophages and early expression of classically polarized (M1) macrophage markers in unpolarized monocyte-derived macrophages (MDMs) in patients with cystic fibrosis (CF). The present study assessed whether the mechanism(s) underlying defective macrophage polarization...

Background: Improved lung function and fewer pulmonary exacerbations (PEx) were observed with lumacaftor/ivacaftor (LUM/IVA) in patients with cystic fibrosis homozygous for F508del. It is unknown whether PEx reduction extends to patients without early lung function improvement. Methods: Post hoc analyses of pooled phase 3 data (NCT01807923, NCT0...

Introduction: Ataxia-Telangiectasia (A-T) is an autosomal recessive multisystem disease affecting the brain, immune system, lungs, liver and also characterised by an enhanced risk of lymphoid and other tumours. At present there is no cure for A-T with management relying on supportive care using symptom-specific medications. Identification of the ge...

Global spread of aggressive mycobacteria Many mycobacteria, in addition to those causing leprosy and tuberculosis, are capable of infecting humans. Some can be particularly dangerous in patients suffering from immunosuppression or chronic disease, such as cystic fibrosis (CF). Bryant et al. observed clusters of near-identical isolates of drug-resis...

Lung infections with $\textit{Mycobacterium abscessus}$, a species of multidrug-resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF), in whom $\textit{M. abscessus}$ accelerates inflammatory lung damage, leading to increased morbidity and mortality. Previously, $\textit{M. absces...

Background: Increased patient longevity and aggressive antibiotic treatment are thought to impact on the microbial composition of the airways of adults with cystic fibrosis (CF). In this study, we sought to determine if a temporal change in the airway microbiology of adults with CF has occurred over time. Methods: Longitudinal analysis of sputum...

This work aimed to develop an in vivo approach for measuring the duration of human bioaerosol infectivity. To achieve this, techniques designed to target short-term and long-term bioaerosol aging, were combined in a tandem system and optimized for the collection of human respiratory bioaerosols, without contamination. To demonstrate the technique,...

Supplement File. (DOCX)

Introduction: Lung disease in cystic fibrosis begins in early life with neutrophil-dominated inflammation and infection, is progressive and results in structural lung damage characterised by bronchial dilation and bronchiectasis. Preventative strategies must be employed in early life but require a better understanding of how bronchiectasis develop...

Background: Lumacaftor/ivacaftor combination therapy has shown clinical benefits in patients with cystic fibrosis homozygous for the Phe508del CFTR mutation; however, pretreatment lung function is a confounding factor that potentially affects the efficacy and safety of this therapy. We aimed to assess the efficacy and safety of lumacaftor/ivacafto...

A systematic review was performed (i) to describe the reported overall rate of progression of CF lung disease quantified as FEV1%predicted decline with age, (ii) to summarise identified influencing risk factors and (iii) to review methods used to analyse CF lung disease progression data. A search of publications providing FEV1%predicted values over...

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...

In cystic fibrosis (CF), Pseudomonas aeruginosa undergoes intra-strain genotypic and phenotypic diversification while establishing and maintaining chronic lung infections. As the clinical significance of these changes is uncertain, we investigated intra-strain diversity in commonly shared strains from CF patients to determine if specific gene mutat...

Nucleotide sequence variation among the 25 Pseudomonas aeruginosa mexZ gene sequences. (PDF)

Sequence variation among the 40 Pseudomonas aeruginosa LasR amino acid sequences. (PDF)

Primer sets used in mexZ and lasR sequencing. (DOCX)

Intra-strain diversity of the mexZ and LasR sequences among the 188 Pseudomonas aeruginosa isolates from 105 patients; 2001–2002 and 2007–2009. (DOCX)

Minimum inhibitory concentrations (mg/L), number of non-susceptible antibiotic results and multidrug resistance among the 74 AUST-02 strain isolates. (DOCX)

The commentary on ivacaftor for patients homozygous for Phe508del-CFTR (c.1521_1523delCTT; formerly F508del) ‘Should we curb our enthusiasm?’ by Jones and Barry makes a number of important points regarding the potential impact of ivacaftor/lumacaftor combination in cystic fibrosis (CF).1 However, the view taken by the authors is rather pessimistic...

Background and objective: The mainstay of treatment for acute bronchiolitis remains supportive care. The objective of this study was to assess the efficacy and safety of nebulized hypertonic saline (HS) in infants with acute bronchiolitis. Methods: Data sources included PubMed and the Virtual Health Library of the Latin American and Caribbean Ce...

The genetic disorder cystic fibrosis is a life-limiting condition affecting ∼70,000 people worldwide. Targeted, early, treatment of the dominant infecting species, Pseudomonas aeruginosa, has improved patient outcomes; however, there is concern that other species are now stepping in to take its place. In addition, the necessarily long-term antibiot...

Modeling of detection limits using the geometric distribution. (A) Empirical and theoretical cumulative probability distributions for taxa in the mock community. Theoretical distributions were calculated as the geometric cumulative probability using the taxon relative abundance as an estimate for the parameter p. Empirical distributions were calcul...

Number of sequences in in silico and 454 amplicon libraries following Acacia correction, and length and quality filtering. (DOC)

Average number of genera detected in mock community samples by extraction method with standard deviation with and without relative abundance threshold. (DOC)

Predicted relative abundance of genera in the simulated mock communities, Komologorov-Smirnov (KS) p-values and 95% confidence sequence cutoffs for detection. The predicted relative abundances were calculated by Grinder by adjusting the input relative abundance and adjusting for copy number bias. The KS test was used to determine whether the empiri...

Normalized real-time PCR data for a subset of non-CF25 samples. Axes show 2∧deltaCT values: CT values for 16 S real-time assay were normalized to the non-human control (NHC), while CT values for the human ERV-3 real-time assay were normalized to the non-microbial control (NMC). A non-template control (NTC) is provided for comparison. (PDF)

Organisms cultured from BAL samples at time of acquisition with colony forming unit (CFU) counts per mL of BAL fluid. (DOC)

Complete Regression Analyses for Predictors of Lung Function (CF-specific FEV1). (DOC)

Complete Logistic Regression Analyses for Predictors of Mucoid P. aeruginosa Infection. (DOC)

Regression Analyses for Lung Function: Assessing the Mediation Effect of P. aeruginosa. (DOC)

Regression Analyses for P. aeruginosa : Assessing the Mediation Effect of Lung Function. (DOC)

Complete Logistic Regression Analyses for Predictors of P. aeruginosa Infection. (DOC)

Derivation of Cystic Fibrosis Twin-Sibling Study (CFTSS) sample and Cystic Fibrosis Foundation Patient Registry (CFF) sample outlining exclusions. (DOC)

Derivation of Australian Cystic Fibrosis Data Registry (ACFDR) sample and Australian Cystic Fibrosis BAL Study (ACFBAL) sample outlining exclusions. (DOC)

Surivial analysis for first positive respiratory culture for Pseudomonas aeruginosa in the CFTSS and ACFBAL samples by temperature quartile. In both study samples, the warmer temperatures were associated with earlier acquisition of P. aeruginosa. (DOC)

Complete Logistic Regression Analyses for Predictors of B. cepacia Complex Infection. (DOC)

Study Outcomes by Temperature Quartile. (DOC)

Newborn screening for cystic fibrosis has become more widespread over the last 5 years with the recent introduction of screening programs across the USA and UK, as well as many other parts of Europe. Most of Australia and New Zealand have had newborn screening programs for more than 15 years. Newborn screening has been shown to improve both short-a...

Claire E Wainwright1,21Royal Children’s Hospital, Brisbane and Queensland, Queensland, Australia; 2Queensland Children’s Medical Research Institute, The University of Queensland, Brisbane, AustraliaThe idea of children as small adults with health care needs that can be managed by extrapolation from adult studies has now largely been abandoned. We n...

Lignocaine, a topical anaesthetic agent, is generally used in variable concentrations usually between 2% and 4% on the vocal cords prior to flexible bronchoscopy and bronchoalveolar lavage (BAL) procedures. The aim of this study was to investigate whether 2% or 1% lignocaine significantly inhibits the growth of organisms commonly found in the respi...

Cystic fibrosis (CF), a common, lethal inherited disease of Caucasians, is a systemic exocrine disorder associated with a dysfunctional chloride channel that restricts or prevents the movement of chloride ions across the apical membrane of epithelial cells [1]. This results in elevated sodium and chloride levels in sweat and airway surface fluid, a...