COPD in Never-Smokers: BOLD Australia Study.

Purpose: Tobacco smoking is the major risk factor for COPD, and it is common for other risk factors in never-smokers to be overlooked. We examined the prevalence of COPD among never-smokers in Australia and identified associated risk factors. Methods: We used data from the Australia Burden of Obstructive Lung Disease (BOLD) study, a cross-section of people aged ≥40 years from six sites. Participants completed interviews and post-bronchodilator spirometry. COPD was primarily defined as an FEV1/FVC ratio <0.70 and secondarily as the ratio less than the lower limit of normal (LLN). Results: The prevalence of COPD in the 1656 never-smokers who completed the study was 10.5% (95% CI: 9.1-12.1%) [ratio

Can We Use Lung Function Thresholds and Respiratory Symptoms to Identify Pre-COPD? A Prospective, Population-based Cohort Study.

RATIONALE: The term 'pre-COPD' refers to individuals at high-risk of developing Chronic Obstructive Pulmonary Disease (COPD) who do not meet conventional spirometric criteria for airflow obstruction. New approaches to identifying these individuals are needed, particularly in younger populations. OBJECTIVE: To determine whether lung function thresholds and respiratory symptoms can be used to identify individuals at-risk of developing COPD. METHODS: The Tasmanian Longitudinal Health Study is a population-based cohort first studied in 1968 (age 7). Respiratory symptoms, pre- and post-bronchodilator (BD) spirometry, diffusing capacity and static lung volumes were measured on a subgroup at age 45, and incidence of COPD was assessed at age 53. For each lung function measure, z-scores were calculated using Global Lung Initiative references. The optimal threshold for best discrimination of COPD incidence was determined by the unweighted Youden Index. MEASUREMENTS AND MAIN RESULTS: Among 801 participants who did not have COPD at age 45, the optimal threshold for COPD incidence by age 53 was pre-BD FEV1/FVC z-score < -1.264, corresponding to the lowest 10th percentile. Those below this threshold had 36-fold increased risk of developing COPD over an eight-year follow-up period (RR 35.8, 95%CI 8.88 to 144), corresponding to a risk difference of +16.4% (95%CI 3.7-67.4). The sensitivity was 88% and specificity 87%. Positive and negative likelihood ratios were 6.79 and 0.14, respectively. Respiratory symptoms, post-BD spirometry, diffusing capacity and static lung volumes did not improve on the classification achieved by pre-BD FEV1/FVC alone. CONCLUSION: Our findings support the inclusion of pre-BD spirometry in the physiological definition of pre-COPD and indicate that pre-BD FEV1/FVC at the 10th percentile accurately identifies individuals at high-risk of developing COPD in community-based settings.

Respiratory Symptoms, Disease Burden, and Quality of Life in Australian Adults According to GOLD Spirometry Grades: Data from the BOLD Australia Study.

Purpose: Population data on the burden of chronic obstructive pulmonary disease (COPD) are often based on patient-reported diagnoses of COPD, emphysema or chronic bronchitis, without spirometry. We aimed to investigate the relationship between health burden, quality of life and severity of airway obstruction in Australian adults aged ≥40 years. Methods: We used data from the BOLD Australia study, which included randomly selected adults aged ≥40 years from six study sites to reflect the sociodemographic and geographic diversity of the Australian population (n = 3522). Participants with post-bronchodilator airflow limitation (ratio of forced expiratory volume in 1 second FEV1 to forced vital capacity <0.7) were grouped by GOLD spirometry grades 1-4. Quality of life was assessed with Short Form 12 (SF-12) Health Survey Questionnaire. Health burden was assessed as lost time off work or social activities, and healthcare utilization. Results: Of the study sample, 2969 participants did not have airflow limitation, 294 (8.4%) were classified as GOLD Grade 1, 212 (6.0%) as GOLD 2 and 43 (1.2%) as GOLD 3-4. Participants with higher GOLD grades had more respiratory symptoms, more comorbidities and greater burden than those with lower GOLD grades. The scores of mental and physical subscales of SF-12 were lower, indicating worse quality of life, from the no airflow limitation group to the GOLD 3-4 group (P = 0.03 and P < 0.001, respectively). Conclusion: Greater airflow limitation is associated with greater burden and poor quality of life. Interventions to prevent, or reduce the level of, airflow limitation will reduce the symptom burden and improve quality of life for patients.

Risk factors and clinical characteristics of breathlessness in Australian adults: Data from the BOLD Australia study.

BACKGROUND: Breathlessness is a common symptom related to a significant health burden. However, the association of breathlessness with clinical characteristics, especially objective pulmonary test results is scarce. We aimed to identify the characteristics independently associated with breathlessness in Australian adults. METHOD: The analysis used data from BOLD Australia, a cross-sectional study that included randomly selected adults aged ≥40 years from six sites in Australia. Clinical characteristics and spirometry results were compared for breathlessness (modified Medical Research Council [mMRC] grade ≥2). RESULTS: Among all respondents (n = 3321), 252 participants (7.6%) reported breathlessness. The main univariate associations were obesity, chronic respiratory diseases, heart diseases and being Indigenous Australians (odds ratios [ORs] = 2.78, 5.20, 3.77 and 4.38, respectively). Participants with breathlessness had lower pre-and post-bronchodilator lung function than those without. Impaired spirometry results including FVC or FEV1 below 80% predicted, or FEV1/FVC < LLN were independently associated with breathlessness (adjusted ORs = 2.66, 2.94 and 2.34, respectively). CONCLUSIONS: Breathlessness is common among Australian adults and is independently associated with obesity, chronic respiratory diseases, heart diseases, being Indigenous Australians, and impaired spirometry. Multi-disciplinary assessment and comprehensive investigation is needed in clinical practice to address the many factors associated with breathlessness in the population.

Clinical characteristics of adults with self-reported diagnosed asthma and/or COPD: data from the BOLD Australia Study.

Background: Diagnosis of asthma and chronic obstructive pulmonary disease (COPD) in the community is variable, often without spirometry. Some studies report that adults with both diagnostic labels (asthma+COPD) have worse health outcomes than those with asthma or COPD only, but data for Australian adults are limited. We investigated the relationship between clinical characteristics and self-reported diagnoses of asthma, COPD and both. Method: We used data from the BOLD Australia study, which included randomly selected adults aged ≥40 years from six study sites. The BOLD questionnaires and spirometry test were used in all sites. Participants were grouped by self-reported diagnosis. Demographic and clinical characteristics and lung function were compared between groups. Results: Of the study sample (n=3522), 336 reported asthma only, 172 reported COPD only, 77 reported asthma+COPD and 2937 reported neither. Fewer than half of participants with a COPD diagnosis (with or without asthma) had airflow limitation. Participants with asthma+COPD had more respiratory symptoms and greater airflow limitation than those with either diagnosis alone. Having asthma+COPD was independently associated with a higher probability of having clinically important breathlessness (modified Medical Research Council score ≥2) than asthma only (adjusted OR 3.44, 95% CI 1.86-6.33) or COPD only (adjusted OR 3.28, 95% CI 1.69-6.39). Airflow limitation (Global Initiative for Chronic Obstructive Lung Disease 2 or higher, using post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ratio <0.7) was similar between asthma only and COPD only, but twice as prevalent in asthma+COPD (adjusted OR 2.18 and 2.58, respectively). Conclusions: Adults with diagnoses of asthma+COPD have a higher symptom and disease burden than those with diagnoses of asthma only or COPD only. These patients should receive regular comprehensive reviews because of the substantially increased burden of having both diagnoses.

Lifetime spirometry patterns of obstruction and restriction, and their risk factors and outcomes: a prospective cohort study.

BACKGROUND: Interest in lifetime lung function trajectories has increased in the context of emerging evidence that chronic obstructive pulmonary disease (COPD) can arise from multiple disadvantaged lung function pathways, including those that stem from poor lung function in childhood. To our knowledge, no previous study has investigated both obstructive and restrictive lifetime patterns concurrently, while accounting for potential overlaps between them. We aimed to investigate lifetime trajectories of the FEV1/forced vital capacity (FVC) ratio, FVC, and their combinations, relate these combined trajectory groups to static lung volume and gas transfer measurements, and investigate both risk factors for and consequences of these combined trajectory groups. METHODS: Using z scores from spirometry measured at ages 7, 13, 18, 45, 50, and 53 years in the Tasmanian Longitudinal Health Study (n=2422), we identified six FEV1/FVC ratio trajectories and five FVC trajectories via group-based trajectory modelling. Based on whether trajectories of the FEV1/FVC ratio and FVC were low (ie, low from childhood or adulthood) or normal, four patterns of lifetime spirometry obstruction or restriction were identified and compared against static lung volumes and gas transfer. Childhood and adulthood characteristics and morbidities of these patterns were investigated. FINDINGS: The prevalence of the four lifetime spirometry patterns was as follows: low FEV1/FVC ratio only, labelled as obstructive-only, 25·8%; low FVC only, labelled as restrictive-only, 10·5%; both low FEV1/FVC ratio and low FVC, labelled as mixed, 3·5%; and neither low FEV1/FVC ratio nor low FVC, labelled as reference, 60·2%. The prevalence of COPD at age 53 years was highest in the mixed pattern (31 [37%] of 84 individuals) followed by the obstructive-only pattern (135 [22%] of 626 individuals). Individuals with the mixed pattern also had the highest prevalence of parental asthma, childhood respiratory illnesses, adult asthma, and depression. Individuals with the restrictive-only pattern had lower total lung capacity and residual volume, and had the highest prevalence of childhood underweight, adult obesity, diabetes, cardiovascular conditions, hypertension, and obstructive sleep apnoea. INTERPRETATION: To our knowledge, this is the first study to characterise lifetime phenotypes of obstruction and restriction simultaneously using objective data-driven techniques and unique life course spirometry measures of FEV1/FVC ratio and FVC from childhood to middle age. Mixed and obstructive-only patterns indicate those who might benefit from early COPD interventions. Those with the restrictive-only pattern had evidence of true lung restriction and were at increased risk of multimorbidity by middle age. FUNDING: National Health and Medical Research Council of Australia, The University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, The Victorian, Queensland & Tasmanian Asthma Foundations, The Royal Hobart Hospital, Helen MacPherson Smith Trust, and GlaxoSmithKline.

Small for gestational age is associated with reduced lung function in middle age: A prospective study from first to fifth decade of life.

BACKGROUND AND OBJECTIVE: The association between birth weight, particularly relative to gestational age, and adult lung function is uncertain. We investigated the associations between birth weight relative to gestational age and measures of lung function in middle age, and mediation of these associations by adult height. METHODS: Participants in the Tasmanian Longitudinal Health Study who had both known birth weight and lung function assessment at age 45 years were included (n = 849). Linear regression models were fitted to investigate the association between small for gestational age and birth weight with post-bronchodilator lung function measures (forced expiratory volume in 1 second [FEV1 ], forced vital capacity [FVC], FEV1 /FVC, diffusing capacity for carbon monoxide [DL co], residual volume [RV] and total lung capacity [TLC]), adjusting for potential confounders. The contribution of adult height as a mediator of these associations was investigated. RESULTS: Compared with infants born with normal weight for gestational age, those born small for gestational age had reduced FEV1 (coefficient: -191 ml [95%CI: -296, -87]), FVC (-205 ml [-330, -81]), TLC (-292 ml [-492, -92]), RV (-126 ml [-253, 0]) and DL co (-0.42 mmol/min/kPa [-0.79, -0.041]) at age 45 years. However, they had comparable FEV1 /FVC. For every 1 kg increase in birth weight, lung function indices increased by an average of 117 ml (95%CI: 40, 196) for FEV1 , 124 ml (30, 218) for FVC, 215 ml (66, 365) for TLC and 0.36 mmol/min/kPa (0.11, 0.62) for DL co, independent of gestational age, but again not for FEV1 /FVC. These associations were significantly mediated by adult height (56%-90%). CONCLUSION: Small for gestational age was associated with reduced lung function that is likely due to smaller lungs with little evidence of any specific parenchymal impairment.

Relationship between concavity of the flow-volume loop and small airway measures in smokers with normal spirometry.

BACKGROUND: There is increasing evidence of small airway abnormalities in smokers despite normal spirometry. The concavity in the descending limb of the maximum expiratory flow curve (MEFV) is a recognised feature of obstruction and can provide information beyond FEV1, and potentially early smoking-related damage. We aimed to evaluate concavity measures compared to known small airway measurements. METHODS: Eighty smokers with normal spirometry had small airway function assessed: multiple breath nitrogen washout (MBNW) from which ventilation heterogeneity in the diffusion-dependent acinar (Sacin) and convection-dependent conductive (Scond) airways were assessed, and impulse oscillometry system (IOS) from which respiratory resistance and reactance at 5 Hz (R5 and X5) were measured. Concavity measures were calculated from the MEFV, partitioned into global and peripheral concavity. RESULTS: We found abnormal peripheral and global concavity as well as acinar ventilation heterogeneity are common in "normal" smokers. Concavity measures were not related to either MBNW or IOS measurements. CONCLUSION: Abnormalities in concavity indices and MBNW or oscillometry parameters are common in smokers despite normal spirometry. However, these measures likely reflect different mechanisms of peripheral airway dysfunction.

Association between very to moderate preterm births, lung function deficits, and COPD at age 53 years: analysis of a prospective cohort study.

BACKGROUND: Prematurity has been linked to reduced lung function up to age 33 years, but its long-term effects on lung function and chronic obstructive pulmonary disease (COPD) are unknown. To address this question, we investigated associations between prematurity, lung function, and COPD in the sixth decade of life using data from the Tasmanian Longitudinal Health Study (TAHS). METHODS: Data were analysed from 1445 participants in the TAHS. Lung function was measured at 53 years of age. Gestational ages were very preterm (28 weeks to <32 weeks), moderate preterm (32 weeks to <34 weeks), late preterm (34 weeks to <37 weeks) and term (≥37 weeks). Linear and logistic regression models were fitted to investigate associations of prematurity with lung function measures (FEV1, forced vital capacity [FVC], FEV1/FVC ratio, forced expiratory flow at 25-75% of FVC [FEF25-75%], diffusing capacity for carbon monoxide [DLCO]) and COPD (post-bronchodilator FEV1/FVC less than the lower limit of normal), adjusting for sex, age, height, parental smoking during pregnancy, number of older siblings, maternal age at birth, and childhood socioeconomic status. Interactions with smoking and asthma were also investigated. RESULTS: Of 3565 individuals with available data on gestational age from the TAHS cohort, 1445 (41%) participants were included in this study, 740 (51%) of whom were female. Compared with term birth, very to moderate preterm birth was significantly associated with an increased risk of COPD at age 53 years (odds ratio 2·9 [95% CI 1·1-7·7]). Very-to-moderate preterm birth was also associated with lower post-bronchodilator FEV1/FVC ratio (beta-coefficient -2·9% [95% CI -4·9 to -0·81]), FEV1 (-190 mL [-339 to -40]), DLCO (-0·55 mmol/min/kPa [-0·97 to -0·13]), and FEF25-75% (-339 mL/s [-664 to -14]). The association between very-to-moderate preterm birth and FEV1/FVC ratio was only significant among smokers (pinteraction=0·0082). Similar findings were observed for moderate preterm birth when analysed as a separate group. Compared with term birth, late preterm birth was not associated with lower FEV1/FVC ratio or COPD. INTERPRETATION: This is the first study to investigate the effect of prematurity on lung function into middle-age. Data show that very-to-moderate prematurity is associated with obstructive lung function deficits including COPD well into the sixth decade of life and that this effect is compounded by personal smoking. FUNDING: National Health and Medical Research Council (NHMRC) of Australia, European Union's Horizon 2020, The University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, The Victorian, Queensland & Tasmanian Asthma Foundations, The Royal Hobart Hospital, Helen MacPherson Smith Trust, and GlaxoSmithKline.

Normal limits for oscillometric bronchodilator responses and relationships with clinical factors.

INTRODUCTION: We aimed to determine normal thresholds for positive bronchodilator responses for oscillometry in an Australian general population sample aged ≥40 years, to guide clinical interpretation. We also examined relationships between bronchodilator responses and respiratory symptoms, asthma diagnosis, smoking and baseline lung function. METHODS: Subjects recruited from Sydney, Melbourne and Busselton, Australia, underwent measurements of spirometry, resistance (R rs6 ) and reactance (X rs6 ) at 6 Hz, before and after inhalation of salbutamol 200 µg. Respiratory symptoms and/or medication use, asthma diagnosis, and smoking were recorded. Threshold bronchodilator responses were defined as the fifth percentile of decrease in R rs6 and 95th percentile increase in X rs6 in a healthy subgroup. RESULTS: Of 1318 participants, 1145 (570 female) were analysed. The lower threshold for ΔR rs6 was -1.38 cmH2O·s·L-1 (-30.0% or -1.42 Z-scores) and upper threshold for ΔX rs6 was 0.57 cmH2O·s·L-1 (1.36 Z-scores). Respiratory symptoms and/or medication use, asthma diagnosis, and smoking all predicted bronchodilator response, as did baseline oscillometry and spirometry. When categorised into clinically relevant groups according to those predictors, ΔX rs6 was more sensitive than spirometry in smokers without current asthma or chronic obstructive pulmonary disease (COPD), ∼20% having a positive response. Using absolute or Z-score change provided similar prevalences of responsiveness, except in COPD, in which responsiveness measured by absolute change was twice that for Z-score. DISCUSSION: This study describes normative thresholds for bronchodilator responses in oscillometry parameters, including intra-breath parameters, as determined by absolute, relative and Z-score changes. Positive bronchodilator response by oscillometry correlated with clinical factors and baseline function, which may inform the clinical interpretation of oscillometry.

Childhood lung function as a determinant of menopause-dependent lung function decline.

RATIONALE: The naturally occurring age-dependent decline in lung function accelerates after menopause, likely due to the change of the endocrine balance. Although increasing evidence shows suboptimal lung health in early life can increase adult  susceptibility to insults, the potential effect of poor childhood lung function on menopause-dependent lung function decline has not yet been investigated. OBJECTIVES: To study whether menopause-dependent lung function decline, assessed as forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), is determined by childhood lung function. METHODS: The Tasmanian Longitudinal Health Study, a cohort born in 1961, underwent spirometry at age seven.  At ages 45 and 50 serum samples, spirometry and questionnaire data were collected (N = 506). We measured follicle stimulating and luteinizing hormones to determine menopausal status using latent profile analysis. The menopause-dependent lung function decline was investigated using linear mixed models, adjusted for anthropometrics, occupational level, smoking, asthma, asthma medication and study year, for the whole study population and stratified by tertiles of childhood lung function. MEASUREMENTS AND MAIN RESULTS: The overall menopause-dependent lung function decline was 19.3 mL/y (95%CI 2.2 to 36.3) for FVC and 9.1 mL/y (-2.8 to 21.0) for FEV1. This was most pronounced (pinteraction=0.03) among women within the lowest tertile of childhood lung function [FVC 22.2 mL/y (1.1 to 43.4); FEV1 13.9 mL/y (-1.5 to 29.4)]. CONCLUSIONS: Lung function declines especially rapidly in postmenopausal women who had poor low lung function in childhood. This provides novel insights into respiratory health during reproductive aging and emphasizes the need for holistic public health strategies covering the whole lifespan.

Prevalence of chronic obstructive pulmonary disease with breathlessness in Australia: weighted using the 2016 Australian census.

Access to up-to-date Australian disease prevalence estimates assists health services and consumer organisations to plan and allocate resources. The Burden of Obstructive Lung Disease study was conducted between 2006 and 2012 and provided chronic obstructive pulmonary disease (COPD) (post-bronchodilator airflow limitation) prevalence estimates weighted to the 2006 Australian census. Using the 2016 Australian census, an updated prevalence estimate of all COPD is 8.30% (95% confidence interval = 6.59%-10.01%) for adults aged 40 or more years in Australia and includes 2.52% with mild breathlessness, 0.99% with moderate breathlessness and 0.91% with severe breathlessness.

Undiagnosed and Misdiagnosed Chronic Obstructive Pulmonary Disease: Data from the BOLD Australia Study.

PURPOSE: Spirometry is necessary to confirm COPD, but many patients are diagnosed based on clinical presentation and/or chest x-ray. There are also those who do not present to primary care for case finding and remain undiagnosed. We aimed to identify: (a) factors that are associated with undiagnosed COPD; and (b) factors that are associated with a potential misdiagnosis of COPD. PATIENTS AND METHODS: This analysis used data from the Burden of Obstructive Lung Disease (BOLD), a cross-sectional study of community dwelling adults randomly selected from six study sites, chosen to provide a representative sample of the Australian population (n= 3357). Participants were grouped by COPD diagnostic criteria based on spirometry and self-reported diagnosis. Odds ratios for predictors of undiagnosed and misdiagnosed were estimated using logistic regression. RESULTS: Of the BOLD Australia sample, 1.8% had confirmed COPD, of whom only half self-reported a diagnosis of COPD. A further 6.9% probably had COPD, but were undiagnosed. The priority target population for case finding of undiagnosed COPD was aged ≥60 years (particularly those ≥75 years), with wheezing, shortness of breath and a body mass index (BMI) <25kg/m2. The priority target population for identifying and reviewing misdiagnosed COPD was aged <60 years, female, with no wheezing and a BMI ≥25kg/m2. CONCLUSION: Challenges continue in accurately diagnosing COPD and greater efforts are needed to identify undiagnosed and misdiagnosed individuals to ensure an accurate diagnosis and the initiation of appropriate management in order to reduce the burden of COPD.

Bronchodilator reversibility as a diagnostic test for adult asthma: findings from the population-based Tasmanian Longitudinal Health Study.

Bronchodilator reversibility (BDR) is often used as a diagnostic test for adult asthma. However, there has been limited assessment of its diagnostic utility. We aimed to determine the discriminatory accuracy of common BDR cut-offs in the context of current asthma and asthma-COPD overlap (ACO) in a middle-aged community sample. The Tasmanian Longitudinal Health Study is a population-based cohort first studied in 1968 (n=8583). In 2012, participants completed respiratory questionnaires and spirometry (n=3609; mean age 53 years). Receiver operating characteristic (ROC) curves were fitted for current asthma and ACO using continuous BDR measurements. Diagnostic parameters were calculated for different categorical cut-offs. Area under the ROC curve (AUC) was highest when BDR was expressed as change in forced expiratory volume in 1 s (FEV1) as a percentage of initial FEV1, as compared with predicted FEV1. The corresponding AUC was 59% (95% CI 54-64%) for current asthma and 87% (95% CI 81-93%) for ACO. Of the categorical cut-offs examined, the European Respiratory Society/American Thoracic Society threshold (≥12% from baseline and ≥200 mL) was assessed as providing the best balance between positive and negative likelihood ratios (LR+ and LR-, respectively), with corresponding sensitivities and specificities of 9% and 97%, respectively, for current asthma (LR+ 3.26, LR- 0.93), and 47% and 97%, respectively, for ACO (LR+ 16.05, LR- 0.55). With a threshold of ≥12% and ≥200 mL from baseline, a positive BDR test provided a clinically meaningful change in the post-test probability of disease, whereas a negative test did not. BDR was more useful as a diagnostic test in those with co-existent post-bronchodilator airflow obstruction (ACO).

Early Age at Natural Menopause Is Related to Lower Post-Bronchodilator Lung Function. A Longitudinal Population-based Study.

Rationale: Poor lung function, a significant predictor of mortality, has been observed in postmenopausal women compared with those still menstruating. Menopausal age is a risk factor for several adverse health outcomes, but little evidence exists on the impact of menopausal age on lung function impairments, especially regarding post-bronchodilator lung function measures.Objectives: To investigate the association between age at menopause and pre- and post-bronchodilator lung function outcomes.Methods: During the sixth-decade follow-up of the Tasmanian Longitudinal Health Study cohort (mean age, 53 yr), information was collected on most recent menstrual period and menopausal status. Lung function was measured at age 7 years and again at 53 years. Multiple linear regression was performed to determine the association between age at menopause and pre- and post-bronchodilator spirometry, controlling for early and adult life confounders.Results: Women reporting an early age at natural menopause (<45 yr) had lower post-bronchodilator forced expiratory volume in 1 second (-168 ml; 95% confidence interval, -273 to -63) and lower forced vital capacity (-186 ml; 95% confidence interval, -302 to -70) than postmenopausal women who experienced menopause at a later age (≥45 yr). No association was observed with forced expiratory volume in 1 second/forced vital capacity ratio. Adjustment for early-life confounders strengthened these associations.Conclusions: This study provides new evidence that early menopause is associated with reduced lung function that is suggestive of restriction, but not obstruction, even after adjustment for early-life confounders. Given the important link between poor lung function and mortality, clinicians should be aware of the risk of diminished lung function in postmenopausal women who experience menopause at an early age.

Early menarche is associated with lower adult lung function: A longitudinal cohort study from the first to sixth decade of life.

BACKGROUND AND OBJECTIVE: Early menarche is increasing in prevalence worldwide, prompting clinical and public health interest on its links with pulmonary function. We aimed to investigate the relationship between early menarche and lung function in middle age. METHODS: The population-based Tasmanian Longitudinal Health Study (born 1961; n = 8583), was initiated in 1968. The 5th Decade follow-up data (mean age: 45 years) included age at menarche and complex lung function testing. The 6th Decade follow-up (age: 53 years) repeated spirometry and gas transfer factor. Multiple linear regression and mediation analyses were performed to determine the association between age at menarche and adult lung function and investigate biological pathways, including the proportion mediated by adult-attained height. RESULTS: Girls reporting an early menarche (<12 years) were measured to be taller with greater lung function at age 7 years compared with those reporting menarche ≥12 years. By 45 years of age, they were shorter and had lower post-bronchodilator (BD) forced expiratory volume in 1 s (adjusted mean difference: -133 mL; 95% CI: -233, -33), forced vital capacity (-183 mL; 95% CI: -300, -65) and functional residual capacity (-168 mL; 95% CI: -315, -21). Magnitudes of spirometric deficits were similar at age 53 years. Forty percent of these total effects were mediated through adult-attained height. CONCLUSION: Early menarche was associated with reduced adult lung function. This is the first study to investigate post-BD outcomes and quantify the partial role of adult height in this association.

Childhood pneumonia, pleurisy and lung function: a cohort study from the first to sixth decade of life.

INTRODUCTION: Adult spirometry following community-acquired childhood pneumonia has variably been reported as showing obstructive or non-obstructive deficits. We analysed associations between doctor-diagnosed childhood pneumonia/pleurisy and more comprehensive lung function in a middle-aged general population cohort born in 1961. METHODS: Data were from the prospective population-based Tasmanian Longitudinal Health Study cohort. Analysed lung function was from ages 7 years (prebronchodilator spirometry only, n=7097), 45 years (postbronchodilator spirometry, carbon monoxide transfer factor and static lung volumes, n=1220) and 53 years (postbronchodilator spirometry and transfer factor, n=2485). Parent-recalled histories of doctor-diagnosed childhood pneumonia and/or pleurisy were recorded at age 7. Multivariable linear and logistic regression were used. RESULTS: At age 7, compared with no episodes, childhood pneumonia/pleurisy-ever was associated with reduced FEV1:FVC for only those with current asthma (beta-coefficient or change in z-score=-0.20 SD, 95% CI -0.38 to -0.02, p=0.028, p interaction=0.036). At age 45, for all participants, childhood pneumonia/pleurisy-ever was associated with a restrictive pattern: OR 3.02 (1.5 to 6.0), p=0.002 for spirometric restriction (FVC less than the lower limit of normal plus FEV1:FVC greater than the lower limit of normal); total lung capacity z-score -0.26 SD (95% CI -0.38 to -0.13), p<0.001; functional residual capacity -0.16 SD (-0.34 to -0.08), p=0.001; and residual volume -0.18 SD (-0.31 to -0.05), p=0.008. Reduced lung volumes were accompanied by increased carbon monoxide transfer coefficient at both time points (z-score +0.29 SD (0.11 to 0.49), p=0.001 and +0.17 SD (0.04 to 0.29), p=0.008, respectively). DISCUSSION: For this community-based population, doctor-diagnosed childhood pneumonia and/or pleurisy were associated with obstructed lung function at age 7 for children who had current asthma symptoms, but with evidence of 'smaller lungs' when in middle age.

Lifetime Risk Factors for Pre- and Post-Bronchodilator Lung Function Decline. A Population-based Study.

Rationale: Interactions between early life and adult insults on lung function decline are not well understood, with most studies investigating prebronchodilator (pre-BD) FEV1 decline.Objectives: To investigate relationships between adult risk factors and pre- and post-BD lung function decline and their potential effect modification by early life and genetic factors.Methods: Multiple regression was used to examine associations between adult exposures (asthma, smoking, occupational exposures, traffic pollution, and obesity) and decline in both pre- and post-BD spirometry (forced expiratory volume in 1 s [FEV1], forced vital capacity [FVC], and FEV1/FVC) between ages 45 and 53 years in the Tasmanian Longitudinal Health Study (n = 857). Effect modification of these relationships by childhood respiratory risk factors, including low childhood lung function and GST (glutathione S-transferase) gene polymorphisms, was investigated.Results: Baseline asthma, smoking, occupational exposure to vapors/gases/dusts/fumes, and living close to traffic were associated with accelerated decline in both pre- and post-BD FEV1. These factors were also associated with FEV1/FVC decline. Occupational exposure to aromatic solvents was associated with pre-BD but not post-BD FEV1 decline. Maternal smoking accentuated the effect of personal smoking on pre- and post-BD FEV1 decline. Lower childhood lung function and having the GSTM1 null allele accentuated the effect of occupational exposure to vapors/gases/dusts/fumes and personal smoking on post-BD FEV1 decline. Incident obesity was associated with accelerated decline in FEV1 and more pronounced in FVC.Conclusions: This study provides new evidence for accentuation of individual susceptibility to adult risk factors by low childhood lung function, GSTM1 genotype, and maternal smoking.

Childhood predictors of lung function trajectories and future COPD risk: a prospective cohort study from the first to the sixth decade of life.

BACKGROUND: Lifetime lung function is related to quality of life and longevity. Over the lifespan, individuals follow different lung function trajectories. Identification of these trajectories, their determinants, and outcomes is important, but no study has done this beyond the fourth decade. METHODS: We used six waves of the Tasmanian Longitudinal Health Study (TAHS) to model lung function trajectories measured at 7, 13, 18, 45, 50, and 53 years. We analysed pre-bronchodilator FEV1 z-scores at the six timepoints using group-based trajectory modelling to identify distinct subgroups of individuals whose measurements followed a similar pattern over time. We related the trajectories identified to childhood factors and risk of chronic obstructive pulmonary disease (COPD) using logistic regression, and estimated population-attributable fractions of COPD. FINDINGS: Of the 8583 participants in the original cohort, 2438 had at least two waves of lung function data at age 7 years and 53 years and comprised the study population. We identified six trajectories: early below average, accelerated decline (97 [4%] participants); persistently low (136 [6%] participants); early low, accelerated growth, normal decline (196 [8%] participants); persistently high (293 [12%] participants); below average (772 [32%] participants); and average (944 [39%] participants). The three trajectories early below average, accelerated decline; persistently low; and below average had increased risk of COPD at age 53 years compared with the average group (early below average, accelerated decline: odds ratio 35·0, 95% CI 19·5-64·0; persistently low: 9·5, 4·5-20·6; and below average: 3·7, 1·9-6·9). Early-life predictors of the three trajectories included childhood asthma, bronchitis, pneumonia, allergic rhinitis, eczema, parental asthma, and maternal smoking. Personal smoking and active adult asthma increased the impact of maternal smoking and childhood asthma, respectively, on the early below average, accelerated decline trajectory. INTERPRETATION: We identified six potential FEV1 trajectories, two of which were novel. Three trajectories contributed 75% of COPD burden and were associated with modifiable early-life exposures whose impact was aggravated by adult factors. We postulate that reducing maternal smoking, encouraging immunisation, and avoiding personal smoking, especially in those with smoking parents or low childhood lung function, might minimise COPD risk. Clinicians and patients with asthma should be made aware of the potential long-term implications of non-optimal asthma control for lung function trajectory throughout life, and the role and benefit of optimal asthma control on improving lung function should be investigated in future intervention trials. FUNDING: National Health and Medical Research Council of Australia; European Union's Horizon 2020; The University of Melbourne; Clifford Craig Medical Research Trust of Tasmania; The Victorian, Queensland & Tasmanian Asthma Foundations; The Royal Hobart Hospital; Helen MacPherson Smith Trust; and GlaxoSmithKline.