Which reference equation should we use for interpreting spirometry values for First Nations Australians? A cross-sectional study.

OBJECTIVES: To evaluate the suitability of the Global Lung Function Initiative (GLI)-2012 other/mixed and GLI-2022 global reference equations for evaluating the respiratory capacity of First Nations Australians. DESIGN, SETTING: Cross-sectional study; analysis of spirometry data collected by three prospective studies in Queensland, the Northern Territory, and Western Australia between March 2015 and December 2022. PARTICIPANTS: Opportunistically recruited First Nations participants in the Indigenous Respiratory Reference Values study (Queensland, Northern Territory; age, 3-25 years; 18 March 2015 - 24 November 2017), the Healthy Indigenous Lung Function Testing in Adults study (Queensland, Northern Territory; 18 years or older; 14 August 2019 - 15 December 2022) and the Many Healthy Lungs study (Western Australia; five years or older; 10 October 2018 - 7 November 2021). MAIN OUTCOME MEASURES: Goodness of fit to spirometry data for each GLI reference equation, based on mean Z-score and its standard deviation, and proportions of participants with respiratory parameter values within 1.64 Z-scores of the mean value. RESULTS: Acceptable and repeatable forced expiratory volume in the first second (FEV1) values were available for 2700 First Nations participants in the three trials; 1467 were classified as healthy and included in our analysis (1062 children, 405 adults). Their median age was 12 years (interquartile range, 9-19 years; range, 3-91 years), 768 (52%) were female, and 1013 were tested in rural or remote areas (69%). Acceptable and repeatable forced vital capacity (FVC) values were available for 1294 of the healthy participants (88%). The GLI-2012 other/mixed and GLI-2022 global equations provided good fits to the spirometry data; the race-neutral GLI-2022 global equation better accounted for the influence of ageing on FEV1 and FVC, and of height on FVC. Using the GLI-2012 other/mixed reference equation and after adjusting for age, sex, and height, mean FEV1 (estimated difference, -0.34; 95% confidence interval [CI], -0.46 to -0.22) and FVC Z-scores (estimated difference, -0.45; 95% CI, -0.59 to -0.32) were lower for rural or remote than for urban participants, but their mean FEV1/FVC Z-score was higher (estimated difference, 0.14; 95% CI, 0.03-0.25). CONCLUSION: The normal spirometry values of healthy First Nations Australians may be substantially higher than previously reported. Until more spirometry data are available for people in urban areas, the race-neutral GLI-2022 global or the GLI-2012 other/mixed reference equations can be used when assessing the respiratory function of First Nations Australians.

Erdosteine in children and adults with bronchiectasis (BETTER trial): study protocol for a multicentre, double-blind, randomised controlled trial.

INTRODUCTION: Bronchiectasis is a worldwide chronic lung disorder where exacerbations are common. It affects people of all ages, but especially Indigenous populations in high-income nations. Despite being a major contributor to chronic lung disease, there are no licensed therapies for bronchiectasis and there remain relatively few randomised controlled trials (RCTs) conducted in children and adults. Our RCT will address some of these unmet needs by evaluating whether the novel mucoactive agent, erdosteine, has a therapeutic role in children and adults with bronchiectasis.Our primary aim is to determine in children and adults aged 2-49 years with bronchiectasis whether regular erdosteine over a 12-month period reduces acute respiratory exacerbations compared with placebo. Our primary hypothesis is that people with bronchiectasis who regularly use erdosteine will have fewer exacerbations than those receiving placebo.Our secondary aims are to determine the effect of the trial medications on quality of life (QoL) and other clinical outcomes (exacerbation duration, time-to-next exacerbation, hospitalisations, lung function, adverse events). We will also assess the cost-effectiveness of the intervention. METHODS AND ANALYSIS: We are undertaking an international multicentre, double-blind, placebo-RCT to evaluate whether 12 months of erdosteine is beneficial for children and adults with bronchiectasis. We will recruit 194 children and adults with bronchiectasis to a parallel, superiority RCT at eight sites across Australia, Malaysia and Philippines. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, exacerbation duration, time-to-next exacerbation, hospitalisations and lung function. ETHICS AND DISSEMINATION: The Human Research Ethics Committees (HREC) of Children's Health Queensland (for all Australian sites), University of Malaya Medical Centre (Malaysia) and St. Luke's Medical Centre (Philippines) approved the study. We will publish the results and share the outcomes with the academic and medical community, funding and relevant patient organisations. TRIAL REGISTRATION NUMBER: ACTRN12621000315819.

Radiographic Outcomes in Paediatric Bronchiectasis and Factors Associated with Reversibility.

RATIONALE: Conventionally considered irreversible, bronchiectasis reversibility in children has been demonstrated in small studies. However, the factors associated with radiographic reversibility in bronchiectasis have yet to be defined. OBJECTIVES: In a large cohort of children with bronchiectasis, we aimed to determine (a) if and to what extent bronchiectasis is reversible and (b) factors associated with radiographic chest high resolution computed tomography (cHRCT) resolution. METHODS: We identified children with bronchiectasis who had a repeat multidetector HRCT between 2010-2021. We excluded those with cystic fibrosis, surgical pulmonary resection, traction bronchiectasis only, or lobar opacification. MAIN RESULTS: cHRCT scans were scored using the modified Reiff-score (MRS) with a paediatric correction. Resolution was defined as absence of abnormal broncho-arterial ratio (>0.8) on the second cHRCT. We included 142 children (median age=5years: IQR 2.6-7.4), Inter- and intra-rater agreement in MRSs was excellent (weighted kappa=0.83-0.86 and 0.95 respectively). Radiographically resolution was documented in 57/142 (40.1%), improved in 56/142 (39.4%), unchanged/worse in 29/142 (20.4%). Pseudomonas aeruginosa (PsA) was absolutely associated with non-resolution. On multivariable regression, in those without PsA cultured, younger age-at-diagnosis (risk ratio (RR)=0.94, 95%CI 0.88-0.99) lower MRS (RR=0.89, 95% CI 0.82-0.97) and lower annual exacerbation rate requiring intravenous antibiotics (RR=0.60, 95%CI 0.37-0.98) increased the likelihood of radiographic resolution. CONCLUSIONS: This first large cohort confirms bronchiectasis in children is often reversible with appropriate management. Younger aged children and those with lesser radiographic severity at diagnosis were most likely to achieve radiographic reversibility whilst those with PsA infection were least likely.

Rasch validation of the short form (8 item) PC-QoL questionnaire and applicability of use as a health state classification system for a new preference-based measure.

BACKGROUND: The parent-proxy paediatric chronic cough quality of life questionnaire (PC-QoL) is a commonly used measure of spillover quality of life in parents of children with chronic cough. To date, spillover health utility in these parents is not routinely estimated largely due to the lack of a suitable instrument. Their perspective is not included in economic evaluations of interventions for their children. We explored developing a health state classification system based on the PC-QoL for measuring health utility spill over in this population. METHODS: This study included PC-QoL 8-item responses of 653 parents participating in a prospective cohort study about paediatric chronic cough. Exploratory factor analysis (EFA) and Rasch analysis were used to examine dimensionality and select potential items and level structure. RESULTS: EFA indicated that the PC-QoL had one underlying domain. Rasch analysis indicated threshold disordering in all items which improved when items were collapsed from seven to four levels. Two demonstrated differential item functioning (DIF) by diagnosis or ethnicity and were excluded from the final scale. This scale satisfied Rasch assumptions of local independence and unidimensionality and demonstrated acceptable fit to the Rasch model. It was presented to and modified by an expert panel and a consumer panel. The resulting classification system had six items, each with four levels. DISCUSSION: The PC-QoL can conform to a Rasch model with minor modifications. It may be a good basis for the classification system of a child cough-specific PBM. A valuation study is required to estimate preference weights for each item and to estimate health utility in parents of children with chronic cough.

Social determinants of respiratory health from birth: still of concern in the 21st century?

Respiratory symptoms are ubiquitous in children and, even though they may be the harbinger of poor long-term outcomes, are often trivialised. Adverse exposures pre-conception, antenatally and in early childhood have lifetime impacts on respiratory health. For the most part, lung function tracks from the pre-school years at least into late middle age, and airflow obstruction is associated not merely with poor respiratory outcomes but also early all-cause morbidity and mortality. Much would be preventable if social determinants of adverse outcomes were to be addressed. This review presents the perspectives of paediatricians from many different contexts, both high and low income, including Europe, the Americas, Australasia, India, Africa and China. It should be noted that there are islands of poverty within even the highest income settings and, conversely, opulent areas in even the most deprived countries. The heaviest burden of any adverse effects falls on those of the lowest socioeconomic status. Themes include passive exposure to tobacco smoke and indoor and outdoor pollution, across the entire developmental course, and lack of access even to simple affordable medications, let alone the new biologicals. Commonly, disease outcomes are worse in resource-poor areas. Both within and between countries there are avoidable gross disparities in outcomes. Climate change is also bearing down hardest on the poorest children. This review highlights the need for vigorous advocacy for children to improve lifelong health. It also highlights that there are ongoing culturally sensitive interventions to address social determinants of disease which are already benefiting children.

Chronic respiratory disease in Indigenous peoples: a framework to address inequity and strengthen respiratory health and health care globally.

Indigenous peoples around the world bear a disproportionate burden of chronic respiratory diseases, which are associated with increased risks of morbidity and mortality. Despite the imperative to address global inequity, research focused on strengthening respiratory health in Indigenous peoples is lacking, particularly in low-income and middle-income countries. Drivers of the increased rates and severity of chronic respiratory diseases in Indigenous peoples include a high prevalence of risk factors (eg, prematurity, low birthweight, poor nutrition, air pollution, high burden of infections, and poverty) and poor access to appropriate diagnosis and care, which might be linked to colonisation and historical and current systemic racism. Efforts to tackle this disproportionate burden of chronic respiratory diseases must include both global approaches to address contributing factors, including decolonisation of health care and research, and local approaches, co-designed with Indigenous people, to ensure the provision of culturally strengthened care with more equitable prioritisation of resources. Here, we review evidence on the burden of chronic respiratory diseases in Indigenous peoples globally, summarise factors that underlie health disparities between Indigenous and non-Indigenous people, propose a framework of approaches to improve the respiratory health of Indigenous peoples, and outline future directions for clinical care and research.

Improving the Diagnosis and Treatment of Paediatric Bronchiectasis Through Research and Translation.

Bronchiectasis, particularly in children, is an increasingly recognised yet neglected chronic lung disorder affecting individuals in both low-to-middle and high-income countries. It has a high disease burden and there is substantial inequity within and between settings. Furthermore, compared with other chronic lung diseases, considerably fewer resources are available for children with bronchiectasis. The need to prevent bronchiectasis and to reduce its burden also synchronously aligns with its high prevalence and economic costs to health services and society. Like many chronic lung diseases, bronchiectasis often originates early in childhood, highlighting the importance of reducing the disease burden in children. Concerted efforts are therefore needed to improve disease detection, clinical management and equity of care. Modifiable factors in the causal pathways of bronchiectasis, such as preventing severe and recurrent lower respiratory infections should be addressed, whilst also acknowledging the role played by social determinants of health. Here, we highlight the importance of early recognition/detection and optimal management of bronchiectasis in children, and outline our research, which is attempting to address important clinical knowledge gaps discussed in a recent workshop. The research is grouped under three themes focussing upon primary prevention, improving diagnosis and disease characterisation, and providing better management. Our hope is that others in multiple settings will undertake additional studies in this neglected field to further improve the lives of people with bronchiectasis. We also provide a resource list with links to help inform consumers and healthcare professionals about bronchiectasis and its recognition and management.

Clinical utility of elective paediatric flexible bronchoscopy and impact on the quality of life: protocol for a single-centre, single-blind, randomised controlled trial.

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.

Endotypes of Paediatric Cough-Do They Exist and Finding New Techniques to Improve Clinical Outcomes.

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.

The utility of elective flexible bronchoscopy to improve quality of life and clinical outcomes for children: A systematic review.

INTRODUCTION: Elective flexible bronchoscopy (FB) is now widely available and standard practice for a variety of indications in children with respiratory conditions. However, there is limited evidence regarding the utility of elective FB in children. This systematic review (SRs) aimed to determine the utility of FB on its impact in clinical decision making and quality of life (QoL). METHODS: We searched Pubmed, Cochrane central register of controlled trials, Embase, World Health Organization Clinical Trials Registry Platform and Cochrane database of SRs from inception to April 20, 2023. We included SRs and randomized controlled trials (RCTs) that used parallel group design (comparing use of elective FB vs. no FB, or a wait-list approach [early FB vs. usual wait FB]) in children aged ≤ 18 years. Our protocol was prospectively registered and used Cochrane methodology for systemic reviews of interventions. RESULTS: Our search identified 859 articles; 102 duplicates were removed, and 753 articles were excluded by title and abstract. Four full text articles were reviewed and subsequently excluded, as none met the inclusion criteria outlined in our patient, intervention, comparator, outcome measures framework. CONCLUSIONS: There is a paucity of high-quality RCT evidence to support the routine use of elective FB in children with respiratory conditions. However, available retrospective and a single prospective study demonstrate the high utility of FB in the elective pediatric setting. REGISTRATION: PROSPERO CRD42021291305.

A core outcome set for bronchiectasis in children and adolescents for use in clinical research: an international consensus study.

Improving the treatment of non-cystic fibrosis bronchiectasis in children and adolescents requires high-quality research with outcomes that meet study objectives and are meaningful for patients and their parents and caregivers. In the absence of systematic reviews or agreement on the health outcomes that should be measured in paediatric bronchiectasis, we established an international, multidisciplinary panel of experts to develop a core outcome set (COS) that incorporates patient and parent perspectives. We undertook a systematic review from which a list of 21 outcomes was constructed; these outcomes were used to inform the development of separate surveys for ranking by parents and patients and by health-care professionals. 562 participants (201 parents and patients from 17 countries, 361 health-care professionals from 58 countries) completed the surveys. Following two consensus meetings, agreement was reached on a ten-item COS with five outcomes that were deemed to be essential: quality of life, symptoms, exacerbation frequency, non-scheduled health-care visits, and hospitalisations. Use of this international consensus-based COS will ensure that studies have consistent, patient-focused outcomes, facilitating research worldwide and, in turn, the development of evidence-based guidelines for improved clinical care and outcomes. Further research is needed to develop validated, accessible measurement instruments for several of the outcomes in this COS.

Association between perinatal and early life exposures and lung function in Australian Indigenous young adults: The Aboriginal Birth Cohort study.

BACKGROUND AND OBJECTIVE: Despite the high burden of respiratory disease amongst Indigenous populations, prevalence data on spirometric deficits and its determinants are limited. We estimated the prevalence of abnormal spirometry in young Indigenous adults and determined its relationship with perinatal and early life factors. METHODS: We used prospectively collected data from the Australian Aboriginal Birth Cohort, a birth cohort of 686 Indigenous Australian singletons. We calculated the proportion with abnormal spirometry (z-score <-1.64) and FEV1 below the population mean (FEV1 % predicted 0 to -2SD) measured in young adulthood. We evaluated the association between perinatal and early life exposures with spirometry indices using linear regression. RESULTS: Fifty-nine people (39.9%, 95%CI 31.9, 48.2) had abnormal spirometry; 72 (49.3%, 95%CI 40.9, 57.7) had a FEV1 below the population mean. Pre-school hospitalisations for respiratory infections, younger maternal age, being overweight in early childhood and being born remotely were associated with reduced FEV1 and FVC (absolute, %predicted and z-score). The association between maternal age and FEV1 and FVC were stronger in women, as was hospitalization for respiratory infections before age 5. Being born remotely had a stronger association with reduced FEV1 and FVC in men. Participants born in a remote community were over 6 times more likely to have a FEV1 below the population mean (odds ratio [OR] 6.30, 95%CI 1.93, 20.59). CONCLUSION: Young Indigenous adults have a high prevalence of impaired lung function associated with several perinatal and early life factors, some of which are modifiable with feasible interventions.

Cough in Children and Adults: Diagnosis, Assessment and Management (CICADA). Summary of an updated position statement on chronic cough in Australia.

INTRODUCTION: Cough is the most common symptom leading to medical consultation. Chronic cough results in significant health care costs, impairs quality of life, and may indicate the presence of a serious underlying condition. Here, we present a summary of an updated position statement on cough management in the clinical consultation. MAIN RECOMMENDATIONS: Assessment of children and adults requires a focused history of chronic cough to identify any red flag cough pointers that may indicate an underlying disease. Further assessment with examination should include a chest x-ray and spirometry (when age > 6 years). Separate paediatric and adult diagnostic management algorithms should be followed. Management of the underlying condition(s) should follow specific disease guidelines, as well as address adverse environmental exposures and patient/carer concerns. First Nations adults and children should be considered a high risk group. The full statement from the Thoracic Society of Australia and New Zealand and Lung Foundation Australia for managing chronic cough is available at https://lungfoundation.com.au/resources/cicada-full-position-statement. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: Algorithms for assessment and diagnosis of adult and paediatric chronic cough are recommended. High quality evidence supports the use of child-specific chronic cough management algorithms to improve clinical outcomes, but none exist in adults. Red flags that indicate serious underlying conditions requiring investigation or referral should be identified. Early and effective treatment of chronic wet/productive cough in children is critical. Culturally specific strategies for facilitating the management of chronic cough in First Nations populations should be adopted. If the chronic cough does not resolve or is unexplained, the patient should be referred to a respiratory specialist or cough clinic.

Pulmonary function outcomes after tuberculosis treatment in children: a systematic review and meta-analysis.

BACKGROUND: Despite tuberculosis (TB) being a curable disease, current guidelines fail to account for the long-term outcomes of post-tuberculosis lung disease-a cause of global morbidity despite successful completion of effective treatment. Our systematic review aimed to synthesise the available evidence on the lung function outcomes of childhood pulmonary tuberculosis (PTB). METHODS: PubMed, ISI Web of Science, Cochrane Library and ProQuest databases were searched for English-only studies without time restriction (latest search date 22 March 2023). Inclusion criteria were (1) patients who had TB with pulmonary involvement at age ≤18 years; (2) pulmonary function tests (PFTs) performed on patients after treatment completion; and (3) observational studies, including cohort and cross-sectional studies. We adhered to the recommendations of the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: From 8040 records, 5 studies were included (involving n=567 children), with spirometry measures from 4 studies included in the meta-analyses. The effect sizes of childhood TB on forced expiratory volume in the first second and forced vital capacity z-scores were estimated to be -1.53 (95% CI -2.65, -0.41; p=0.007) and -1.93 (95% CI -3.35, -0.50; p=0.008), respectively. DISCUSSION: The small number of included studies reflects this under-researched area, relative to the global burden of TB. Nevertheless, as childhood PTB impacts future lung function, PFTs (such as spirometry) should be considered a routine test when evaluating the long-term lung health of children beyond their completion of TB treatment. PROSPERO registration number CRD42021250172.

Influence of frame rate in detecting oropharyngeal aspiration in paediatric videofluoroscopic swallow studies - An observational study.

OBJECTIVES: The videofluoroscopic swallow study (VFSS), currently the gold standard for assessing aspiration in children, incurs radiation. Adhering to the ALARA principle is crucial in minimising radiation dose whilst obtaining accurate diagnostic information in children. International adult VFSS guidelines recommend a capture rate of 30 frames per second (fps). Higher capture rates increase radiation yet there is limited evidence on best practice VFSS capture rates in children, particularly on thin fluid consistency-the fastest viscosity with the highest potential for missed aspiration on slower capture rates. We aimed to determine if image acquisition at 30fps versus 15fps alters the accuracy of detecting aspiration when assessing thin fluids during paediatric VFSS. MATERIALS & METHODS: Seventeen speech language pathologists (SLPs) blindly rated a total of 2,356 swallow loops for the presence/absence of aspiration from VFSS recordings of 13 infants/children drinking thin fluids. 76 swallow loops were randomly presented at 15 versus 30fps, on two occasions. Area under receiver operating curve (aROCs) was used to compare the accuracy of aspiration ratings at 15 versus 30fps compared to a comparison set. The intraclass correlation coefficient (ICC) was used to examine rater reliability. RESULTS: Accuracy for detecting aspiration was near-identical at 15fps (aROC:0.97; 95%CI:0.96-0.97) and 30fps (0.96; 95%CI 0.96-0.97). Good inter-rater (ICC:0.82; 95%CI:0.72-0.89) and intra-rater reliability among the raters (ICC:0.89; 95%CI:0.82-0.93) was found. CONCLUSION: Using 15fps in paediatric VFSS when assessing thin fluid consistency aspiration provides a similar detection rate to using 30fps. As 15fps would have a lower radiation dose than 30fps, we recommend using 15fps when undertaking VFSS in children. CLINICAL RELEVANCE STATEMENT: Adhering to the ALARA principles, a capture rate of 15fps should be used in paediatric VFSS for assessment on thin fluids.

Association of novel adult cough subclasses with clinical characteristics and lung function across six decades of life in a prospective, community-based cohort in Australia: an analysis of the Tasmanian Longitudinal Health Study (TAHS).

BACKGROUND: Cough is a common yet heterogeneous condition. Little is known about the characteristics and course of cough in general populations. We aimed to investigate cough subclasses, their characteristics from childhood across six decades of life, and potential treatable traits in a community-based cohort. METHODS: For our analysis of the Tasmanian Longitudinal Health Study (TAHS), a prospective, community-based cohort study that began on Feb 23, 1968, and has so far followed up participants in Tasmania, Australia, at intervals of 10 years from a mean age of 7 years to a mean age of 53 years, we used data collected as part of the TAHS to distinguish cough subclasses among current coughers at age 53 years. For this analysis, participants who answered Yes to at least one cough-related question via self-report questionnaire were defined as current coughers and included in a latent class analysis of cough symptoms; participants who answered No to all nine cough-related questions were defined as non-coughers and excluded from this analysis. Two groups of longitudinal features were assessed from age 7 years to age 53 years: previously established longitudinal trajectories of FEV1, forced vital capacity [FVC], FEV1/FVC ratio, asthma, and allergies-identified via group-based trajectory analysis or latent class analysis-and symptoms at different timepoints, including asthma, current productive cough, ever chronic productive cough, current smoking, and second-hand smoking. FINDINGS: Of 8583 participants included at baseline in the TAHS, 6128 (71·4%) were traced and invited to participate in a follow-up between Sept 3, 2012, and Nov 8, 2016; 3609 (58·9%) of these 6128 returned the cough questionnaire. The mean age of participants in this analysis was 53 years (SD 1·0). 2213 (61·3%) of 3609 participants were defined as current coughers and 1396 (38·7%) were categorised as non-coughers and excluded from the latent class analysis. 1148 (51·9%) of 2213 participants in this analysis were female and 1065 (48·1%) were male. Six distinct cough subclasses were identified: 206 (9·3%) of 2213 participants had minimal cough, 1189 (53·7%) had cough with colds only, 305 (13·8%) had cough with allergies, 213 (9·6%) had intermittent productive cough, 147 (6·6%) had chronic dry cough, and 153 (6·9%) had chronic productive cough. Compared with people with minimal cough, and in contrast to other cough subclasses, people in the chronic productive cough and intermittent productive cough subclasses had worse lung function trajectories (FEV1 persistent low trajectory 2·9%, 6·4%, and 16·1%; p=0·0011, p<0·0001; FEV1/FVC early low-rapid decline trajectory 2·9%, 12·1%, and 13·0%; p=0·012, p=0·0007) and a higher prevalence of cough (age 53 years 0·0%, 32·4% [26·1-38·7], and 50·3% [42·5-58·2]) and asthma (age 53 years 6·3% [3·7-10·6], 26·9% [21·3-33·3], and 41·7% [24·1-49·7]) from age 7 years to age 53 years. INTERPRETATION: We identified potential treatable traits for six cough subclasses (eg, asthma, allergies, and active and passive smoking for productive cough). The required management of productive cough in primary care (eg, routine spirometry) might differ from that of dry cough if our findings are supported by other studies. Future population-based studies could apply our framework to address the heterogeneity and complexity of cough in the community. FUNDING: The National Health and Medical Research Council of Australia, The University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, Victorian Asthma Foundation, Queensland Asthma Foundation, Tasmanian Asthma Foundation, The Royal Hobart Hospital Research Foundation, the Helen MacPherson Smith Trust, GlaxoSmithKline, and the China Scholarship Council.

Clinical determinants for State-Trait Anxiety Inventory of the parents of children with respiratory problems.

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.

Randomised controlled trial of perinatal vitamin D supplementation to prevent early-onset acute respiratory infections among Australian First Nations children: the 'D-Kids' study protocol.

INTRODUCTION: Globally, acute respiratory infections (ARIs) are a leading cause of childhood morbidity and mortality. While ARI-related mortality is low in Australia, First Nations infants are hospitalised with ARIs up to nine times more often than their non-First Nations counterparts. The gap is widest in the Northern Territory (NT) where rates of both acute and chronic respiratory infection are among the highest reported in the world. Vitamin D deficiency is common among NT First Nations neonates and associated with an increased risk of ARI hospitalisation. We hypothesise that perinatal vitamin D supplementation will reduce the risk of ARI in the first year of life. METHODS AND ANALYSIS: 'D-Kids' is a parallel (1:1), double-blind (allocation concealed), randomised placebo-controlled trial conducted among NT First Nations mother-infant pairs. Pregnant women and their babies (n=314) receive either vitamin D or placebo. Women receive 14 000 IU/week or placebo from 28 to 34 weeks gestation until birth and babies receive 4200 IU/week or placebo from birth until age 4 months. The primary outcome is the incidence of ARI episodes receiving medical attention in the first year of life. Secondary outcomes include circulating vitamin D level and nasal pathogen prevalence. Tertiary outcomes include infant immune cell phenotypes and challenge responses. Blood, nasal swabs, breast milk and saliva are collected longitudinally across four study visits: enrolment, birth, infant age 4 and 12 months. The sample size provides 90% power to detect a 27.5% relative reduction in new ARI episodes between groups. ETHICS AND DISSEMINATION: This trial is approved by the NT Human Research Ethics Committee (2018-3160). Study outcomes will be disseminated to participant families, communities, local policy-makers, the broader research and clinical community via written and oral reports, education workshops, peer-reviewed journals, national and international conferences. TRIAL REGISTRATION NUMBER: ACTRN12618001174279.