Neonatal Vitamin D and Associations with Longitudinal Changes of Eczema up to 25 Years of Age.

BACKGROUND: Early-life vitamin D is a potentially modifiable risk factor for the development of eczema, but there is a lack of data on longitudinal associations. METHOD: We measured 25(OH)D3 levels from neonatal dried blood spots in 223 high-allergy-risk children. Latent class analysis was used to define longitudinal eczema phenotype up to 25 years (4 subclasses). Skin prick tests (SPTs) to 6 allergens and eczema outcomes at 6 time points were used to define eczema/sensitization phenotypes. Associations between 25(OH)D3 and prevalent eczema and eczema phenotypes were assessed using logistic regression models. RESULTS: Median 25(OH)D3 level was 32.5 nmol/L (P25-P75 = 23.1 nmol/L). Each 10 nmol/L increase in neonatal 25(OH)D3 was associated with a 26% reduced odds of early-onset persistent eczema (adjusted multinomial odds ratio (aMOR) = 0.74, 95% CI = 0.56-0.98) and 30% increased odds of early-onset-resolving eczema (aMOR = 1.30, 95% CI = 1.05-1.62) when compared to minimal/no eczema up to 12 years. Similar associations were seen for eczema phenotype up to 25 years. We did not see any strong evidence for the association between neonatal 25(OH)D3 and prevalent eczema or eczema/sensitization phenotype. CONCLUSIONS: Higher neonatal 25(OH)D3 levels, a reflection of maternal vitamin D levels in pregnancy, may reduce the risk of early-onset persistent eczema.

Longitudinal peanut and Ara h 2 specific-IgE, -IgG4, and -IgG4/-IgE ratios are associated with the natural resolution of peanut allergy in childhood.

BACKGROUND: There are no studies of longitudinal immunoglobulin measurements in a population-based cohort alongside challenge-confirmed peanut allergy outcomes. Little is known about biomarkers for identifying naturally resolving peanut allergy during childhood. OBJECTIVES: To measure longitudinal trends in whole peanut and component Ara h 2 sIgE and sIgG4 in the first 10 years of life, in a population cohort of children with challenge-confirmed peanut allergy, and to determine whether peanut-specific immunoglobulin levels or trends are associated with peanut allergy persistence or resolution by 10 years of age. METHODS: One-year-old infants with challenge-confirmed peanut allergy (n = 156) from the HealthNuts study (n = 5276) were prospectively followed at ages 4, 6, and 10 years with questionnaires, skin prick tests, oral food challenges, and plasma total-IgE, sIgE and sIgG4 to peanut and Ara h 2. RESULTS: Peanut allergy resolved in 33.9% (95% CI = 25.3%, 43.3%) of children by 10 years old with most resolving (97.4%, 95% CI = 86.5%, 99.9%) by 6 years old. Decreasing Ara h 2 sIgE (p = .01) and increasing peanut sIgG4 (p < .001), Ara h 2 sIgG4 (p = .01), peanut sIgG4/sIgE (p < .001) and Ara h 2 sIgG4/sIgE (p < .001) from 1 to 10 years of age were associated with peanut allergy resolution. Peanut sIgE measured at 1 year old had the greatest prognostic value (AUC = 0.75 [95% CI = 0.66, 0.82]); however, no single threshold produced both high sensitivity and specificity. CONCLUSION: One third of infant peanut allergy resolved by 10 years of age. Decreasing sIgE and sIgG4 to peanut and Ara h 2 over time were associated with natural resolution of peanut allergy. However, biomarker levels at diagnosis were not strongly associated with the natural history of peanut allergy.

The Prevalence of IgE-Mediated Food Allergy and Other Allergic Diseases in the First 10 Years: The Population-Based, Longitudinal HealthNuts Study.

BACKGROUND: There are limited longitudinal data on the population prevalence of allergic conditions during childhood, and few studies have incorporated the reference standard oral food challenge to confirm food allergy. OBJECTIVE: To describe the population prevalence of IgE-mediated food allergy, eczema, asthma, and rhinitis at ages 6 and 10 years in Melbourne, Australia. METHODS: The HealthNuts study recruited 5,276 1-year-old infants in Melbourne, Australia, with repeat assessments at ages 6 and 10 years. At ages 6 and 10 years, carers completed a questionnaire on symptoms and doctor diagnosis of allergic conditions (International Study of Asthma and Allergies in Children). Children were invited to attend a clinic assessment including skin prick test, lung function tests, and oral food challenges when indicated. To minimize the impact of attrition bias, prevalence estimates among participants at ages 6 and 10 years were weighted to reflect characteristics of the whole cohort at recruitment. RESULTS: In total, 4,455 and 4,065 families participated at ages 6 and 10 years, respectively (84% and 77% of the original cohort). Of those, 73% and 55% of participants ages 6 and 10 years, respectively, completed clinical assessments. Overall, 36.5% (95% CI, 34.8-38.2) and 38.2% (95% CI, 36.5-40.1%) of 6- and 10-year-olds had at least one current allergic disease, and around one third of those had two or more allergic diseases. Food allergy occurred in 6.4% (95% CI, 5.6-7.2) of 6-year olds and 6.3% (95% CI, 5.5-7.2) of 10-year-olds. Among infants with challenge-confirmed food allergy in infancy, 45% had persistent disease at age 10 years. The prevalence of current diagnosed asthma at ages 6 and 10 years were 12.1% (95% CI, 10.9-13.3) and 13.1% (95% CI, 11.9-14.4), respectively, current eczema decreased slightly from 15.3% (95% CI, 14.1-19.7) at age 6 years to 12.9% (95% CI, 11.7-14.2) at age 10 years, and current rhinitis increased from 15.1% (95% CI, 13.9-16.5) at age 6 years to 25.0% (95% CI, 23.4-26.7) at age 10 years. CONCLUSIONS: Allergic diseases affect 40% of primary school-age children; one third have multiple allergic diagnoses. Challenge-confirmed food allergy prevalence remains high, and 45% of infants with food allergy have persistent disease to age 10 years.

Chronic Bronchitis in Children and Adults: Definitions, Pathophysiology, Prevalence, Risk Factors, and Consequences.

The complex nature of chronic bronchitis (CB) and changing definitions have contributed to challenges in understanding its aetiology and burden. In children, CB is characterised by persistent airway inflammation often linked to bacterial infections and is therefore termed "protracted bacterial bronchitis" (PBB). Longitudinal studies suggest that CB in childhood persists into adulthood in a subgroup. It can also be associated with future chronic respiratory diseases including asthma, bronchiectasis, and chronic obstructive pulmonary disease (COPD). Adult CB is traditionally associated with smoking, occupational exposures, and lower socioeconomic status. The interplay between risk factors, childhood CB, adult CB, and other chronic respiratory diseases is intricate, requiring comprehensive longitudinal studies for a clearer understanding of the natural history of CB across the lifespan. Such longitudinal studies have been scarce to date given the logistic challenges of maintaining them over time. In this review, we summarise current evidence on the evolution of the definitions, pathophysiology, risk factors, and consequences of childhood and adulthood chronic bronchitis.

Lung-function trajectories: relevance and implementation in clinical practice.

Lung development starts in utero and continues during childhood through to adolescence, reaching its peak in early adulthood. This growth is followed by gradual decline due to physiological lung ageing. Lung-function development can be altered by several host and environmental factors during the life course. As a result, a range of lung-function trajectories exist in the population. Below average trajectories are associated with respiratory, cardiovascular, metabolic, and mental health comorbidities, as well as with premature death. This Review presents progressive research into lung-function trajectories and assists the implementation of this knowledge in clinical practice as an innovative approach to detect poor lung health early, monitor respiratory disease progression, and promote lung health. Specifically, we propose that, similar to paediatric height and weight charts used globally to monitor children's growth, lung-function charts could be used for both children and adults to monitor lung health status across the life course. To achieve this proposal, we introduce our free online Lung Function Tracker tool. Finally, we discuss challenges and opportunities for effective implementation of the trajectory concept at population level and outline an agenda for crucial research needed to support such implementation.

Do early-life allergic sensitization and respiratory infection interact to increase asthma risk?

OBJECTIVE: The 'two-hit' hypothesis theorizes that early life allergic sensitization and respiratory infection interact to increase asthma risk. METHODS: We sought to determine in a high allergy risk birth cohort whether interactions between early life allergic sensitization and respiratory infection were associated with increased risk for asthma at ages 6-7 years and 18 years. Allergic sensitization was assessed at 6, 12, and 24 months by skin prick testing to 3 food and 3 aeroallergens. Respiratory infection was defined as reported "cough, rattle, or wheeze" and assessed 4-weekly for 15 months, at 18 months, and age 2 years. Regression analysis was undertaken with parent-reported asthma at age 6-7 years and doctor diagnosed asthma at 18 years as distinct outcomes. Interactions between allergic sensitization and respiratory infection were explored with adjustment made for potential confounders. RESULTS: Odds of asthma were higher in sensitized compared to nonsensitized children at age 6-7 years (OR = 14.46; 95% CI 3.99-52.4), There was no evidence for interactions between allergic sensitization and early life respiratory infection, with a greater frequency of respiratory infection up to 2 years of age associated with increased odds for asthma at age 6-7 years in both sensitized (OR = 1.13; 95% CI 1.02-1.25, n = 199) and nonsensitized children (OR = 1.31; 1.11-1.53, n = 211) (p interaction = 0.089). At age 18 years, these associations were weaker. CONCLUSIONS: Our findings do not support 'two-hit' interactions between early life allergic sensitization and respiratory infection on asthma risk. Both early life respiratory infections and allergic sensitization were risk factors and children with either should be monitored closely for development of asthma.

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.

Effects of testosterone and sex hormone binding globulin on lung function in males and females: a multivariable Mendelian Randomisation study.

BACKGROUND: Observational studies suggest that total testosterone (TT) and sex hormone-binding globulin (SHBG) may have beneficial effects on lung function, but these findings might be spurious due to confounding and reverse causation. We addressed these limitations by using multivariable Mendelian randomisation (MVMR) to investigate the independent causal effects of TT and SHBG on lung function. METHODS: We first identified genetic instruments by performing genome-wide association analyses of TT and SHBG in the large UK Biobank, separately in males and females. We then assessed the independent effects of TT and SHBG on forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC using one-sample MVMR. We addressed pleiotropy, which could bias MVMR, using several methods that account for it. We performed subgroup MVMR analyses by obesity, physical activity and menopausal status, and assessed associations between TT and SHBG with lung function decline. Finally, we compared the MVMR results with those of observational analyses in the UK Biobank. FINDINGS: In the MVMR analyses, there was evidence of pleiotropy, but results were consistent when accounting for it. We found a strong beneficial effect of TT on FVC and FEV1 in both males and females, but a moderate detrimental effect of SHBG on FEV1 and FEV1/FVC in males only. Subgroup analyses suggested stronger effects of TT among obese and older males. The observational analyses, in line with previous studies, agreed with MRMV for TT, but not for SHBG. INTERPRETATION: These findings suggest that testosterone improves lung function in males and females, while SHBG has an opposite independent effect in males.

Epigenome-Wide Association Studies of COPD and Lung Function: A Systematic Review.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) results from gene-environment interactions over the lifetime. These interactions are captured by epigenetic changes, such as DNA methylation. This systematic review synthesizes evidence from epigenome-wide association studies (EWAS) related to COPD and lung function. METHODS: Systematic literature search on PubMed, Embase and CINAHL databases, identified 1947 articles that investigated epigenetic changes associated with COPD/lung function; 17 of them met our eligibility criteria from which data was manually extracted. Differentially methylated positions (DMPs) and/or annotated genes, were considered replicated if identified by ≥2 studies with a p<1 x 10-4. RESULTS: Ten studies profiled DNA methylation changes in blood and 7 in respiratory samples, including surgically resected lung tissue (n=3), small airways epithelial brushings (n=2), bronchoalveolar lavage (n=1) and sputum (n=1). Main results showed: (1) high variability in study design, covariates and effect sizes, which prevented a formal meta-analysis; (2) in blood samples, 51 DMPs were replicated in relation to lung function and 12 related to COPD; (3) in respiratory samples, 42 DMPs were replicated in relation to COPD but none in relation to lung function; and, (4) in COPD vs. control studies, 123 genes (2.6% of total) were shared between ≥1 blood and ≥1 respiratory sample and associated with chronic inflammation, ion transport and coagulation. CONCLUSIONS: There is high heterogeneity across published COPD/lung function EWAS studies. A few genes (n=123; 2.6%) were replicated in blood and respiratory samples, suggesting that blood can recapitulate some changes in respiratory tissues. These findings have implications for future research.

Comprehensive analysis of environmental exposure to hazardous trace elements and lung function: a national cross-sectional study.

BACKGROUND: There is growing interest in the joint effects of hazardous trace elements (HTEs) on lung function deficits, but the data are limited. This is a critical research gap given increased global industrialisation. METHODS: A national cross-sectional study including spirometry was performed among 2112 adults across 11 provinces in China between 2020 and 2021. A total of 27 HTEs were quantified from urine samples. Generalised linear models and quantile-based g-computation were used to explore the individual and joint effects of urinary HTEs on lung function, respectively. RESULTS: Overall, there were negative associations between forced expiratory volume in 1 s (FEV1) and urinary arsenic (As) (z-score coefficient, -0.150; 95% CI, -0.262 to -0.038 per 1 ln-unit increase), barium (Ba) (-0.148, 95% CI: -0.258 to -0.039), cadmium (Cd) (-0.132, 95% CI: -0.236 to -0.028), thallium (Tl) (-0.137, 95% CI: -0.257 to -0.018), strontium (Sr) (-0.147, 95% CI: -0.273 to -0.022) and lead (Pb) (-0.121, 95% CI: -0.219 to -0.023). Similar results were observed for forced vital capacity (FVC) with urinary As, Ba and Pb and FEV1/FVC with titanium (Ti), As, Sr, Cd, Tl and Pb. We found borderline associations between the ln-quartile of joint HTEs and decreased FEV1 (-20 mL, 95% CI: -48 to +8) and FVC (-14 mL, 95% CI: -49 to+2). Ba and Ti were assigned the largest negative weights for FEV1 and FVC within the model, respectively. CONCLUSION: Our study investigating a wide range of HTEs in a highly polluted setting suggests that higher urinary HTE concentrations are associated with lower lung function, especially for emerging Ti and Ba, which need to be monitored or regulated to improve lung health.

Lung function changes in children exposed to mine fire smoke in infancy.

BACKGROUND AND OBJECTIVE: Chronic, low-intensity air pollution exposure has been consistently associated with reduced lung function throughout childhood. However, there is limited research regarding the implications of acute, high-intensity air pollution exposure. We aimed to determine whether there were any associations between early life exposure to such an episode and lung growth trajectories. METHODS: We conducted a prospective cohort study of children who lived in the vicinity of the Hazelwood coalmine fire. Lung function was measured using respiratory oscillometry. Z-scores were calculated for resistance (R5 ) and reactance at 5 Hz (X5 ) and area under the reactance curve (AX). Two sets of analyses were conducted: (i) linear regression to assess the cross-sectional relationship between post-natal exposure to mine fire-related particulate matter with an aerodynamic diameter of less than 2.5 micrometres (PM2.5 ) and lung function at the 7-year follow-up and (ii) linear mixed-effects models to determine whether there was any association between exposure and changes in lung function between the 3- and 7-year follow-ups. RESULTS: There were no associations between mine fire-related PM2.5 and any of the lung function measures, 7-years later. There were moderate improvements in X5 (ß: -0.37 [-0.64, -0.10] p = 0.009) and AX (ß: -0.40 [-0.72, -0.08] p = 0.014), between the 3- and 7-year follow-ups that were associated with mean PM2.5 , in the unadjusted and covariance-adjusted models. Similar trends were observed with maximum PM2.5 . CONCLUSION: There was a moderate improvement in lung stiffness of children exposed to PM2.5 from a local coalmine fire in infancy, consistent with an early deficit in lung function at 3-years after the fire that had resolved by 7-years.

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.

Spirometric patterns in young and middle-aged adults: a 20-year European study.

BACKGROUND: Understanding the natural history of abnormal spirometric patterns at different stages of life is critical to identify and optimise preventive strategies. We aimed to describe characteristics and risk factors of restrictive and obstructive spirometric patterns occurring before 40 years (young onset) and between 40 and 61 years (mid-adult onset). METHODS: We used data from the population-based cohort of the European Community Respiratory Health Survey (ECRHS). Prebronchodilator forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were assessed longitudinally at baseline (ECRHS1, 1993-1994) and again 20 years later (ECRHS3, 2010-2013). Spirometry patterns were defined as: restrictive if FEV1/FVC≥LLN and FVC<10th percentile, obstructive if FEV1/FVC

Global, regional, and national burden of ischemic heart disease attributable to ambient PM2.5 from 1990 to 2019: An analysis for the global burden of disease study 2019.

Information on the spatio-temporal patterns of the burden of ischemic heart disease (IHD) caused by ambient ambient fine particulate matter (PM2.5) in the global level is needed to prioritize the control of ambient air pollution and prevent the burden of IHD. The Global Burden of Disease Study (GBD) 2019 provides data on IHD attributable to ambient PM2.5. The IHD burden and mortality attributable to ambient PM2.5 were analyzed by year, age, gender, socio-demographic index (SDI) level, geographical region and country. Estimated annual percentage change (EAPC) was calculated to estimate the temporal trends of age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years rate (ASDR) from 1990 to 2019. Globally, the ASMR and ASDR for ambient PM2.5-related IHD tended to level off generally, with EAPC of -0.03 (95% CI: -0.06, 0.12) and 0.3 (95% CI: 0.22, 0.37), respectively. In the past 30 years, there were obvious differences in the trend of burden change among different regions. A highest increased burden was estimated in low-middle SDI region (EAPC of ASMR: 3.73 [95% CI: 3.56, 3.9], EAPC of ASDR: 3.83 [95% CI: 3.64, 4.02]). In contrast, the burden in high SDI region (EAPC of ASMR: -4.48 [95% CI: -4.6, -4.35], EAPC of ASDR: -3.98 [95% CI: -4.12, -3.85]) has declined most significantly. Moreover, this burden was higher among men and older populations. EAPCs of the ASMR (R = -0.776, p < 0.001) and ASDR (R = -0.781, p < 0.001) of this burden had significant negative correlations with the countries' SDI level. In summary, although trends in the global burden of IHD attributable to ambient PM2.5 are stabilizing, but this burden has shifted from high SDI countries to middle and low SDI countries, especially among men and elderly populations. To reduce this burden, the air pollution management prevention need to be further strengthened, especially among males, older populations, and middle and low SDI countries.

Associations of early life and childhood risk factors with obstructive sleep apnoea in middle-age.

BACKGROUND AND OBJECTIVE: Early-life risk factors for obstructive sleep apnoea (OSA) are poorly described, yet this knowledge may be critical to inform preventive strategies. We conducted the first study to investigate the association between early-life risk factors and OSA in middle-aged adults. METHODS: Data were from population-based Tasmanian Longitudinal Health Study cohort (n = 3550) followed from 1st to 6th decades of life. Potentially relevant childhood exposures were available from a parent-completed survey at age 7-years, along with previously characterized risk factor profiles. Information on the primary outcome, probable OSA (based on a STOP-Bang questionnaire cut-off ≥5), were collected when participants were 53 years old. Associations were examined using logistic regression adjusting for potential confounders. Analyses were repeated using the Berlin questionnaire. RESULTS: Maternal asthma (OR = 1.5; 95% CI 1.1-2.0), maternal smoking (OR = 1.2; 1.05, 1.5), childhood pleurisy/pneumonia (OR = 1.3; 1.04, 1.7) and frequent bronchitis (OR = 1.2; 1.01, 1.5) were associated with probable OSA. The risk-factor profiles of 'parental smoking' and 'frequent asthma and bronchitis' were also associated with probable OSA (OR = 1.3; 1.01, 1.6 and OR = 1.3; 1.01-1.9, respectively). Similar associations were found for Berlin questionnaire-defined OSA. CONCLUSIONS: We found novel temporal associations of maternal asthma, parental smoking and frequent lower respiratory tract infections before the age of 7 years with adult OSA. While determination of their pathophysiological and any causal pathways require further research, these may be useful to flag the risk of OSA within clinical practice and create awareness and vigilance among at-risk groups.

Using individual approach to examine the association between urban heat island and preterm birth: A nationwide cohort study in China.

BACKGROUND: Evidence suggests that maternal exposure to heat might increase the risk of preterm birth (PTB), but no study has investigated the effect from urban heat island (UHI) at individual level. AIMS: Our study aimed to investigate the association between individual UHI exposure and PTB. METHODS: We utilized data from the ongoing China Birth Cohort Study (CBCS), encompassing 103,040 birth records up to December 2020. UHI exposure was estimated for each participant using a novel individual assessment method based on temperature data and satellite-derived land cover data. We used generalized linear mixed-effects models to estimate the association between UHI exposure and PTB, adjusting for potential confounders including maternal characteristics and environmental factors. RESULTS: Consistent and statistically significant associations between UHI exposure and PTB were observed up to 21 days before birth. A 5 °C increment in UHI exposure was associated with 27 % higher risk (OR = 1.27, 95 % confident interval: 1.20, 1.34) of preterm birth in lagged day 1. Stratified analysis indicated that the associations were more pronounced in participants who were older, had higher pre-pregnancy body mass index level, of higher socioeconomic status and living in greener areas. CONCLUSION: Maternal exposure to UHI was associated with increased risk of PTB. These findings have implications for developing targeted interventions for susceptible subgroups of pregnant women. More research is needed to validate our findings of increased risk of preterm birth due to UHI exposure among pregnant women.

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.

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.