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.

Association between physical activity over a 10-year period and current insomnia symptoms, sleep duration and daytime sleepiness: a European population-based study.

OBJECTIVES: To explore the relationship between physical activity over a 10-year period and current symptoms of insomnia, daytime sleepiness and estimated sleep duration in adults aged 39-67. DESIGN: Population-based, multicentre cohort study. SETTING: 21 centres in nine European countries. METHODS: Included were 4339 participants in the third follow-up to the European Community Respiratory Health Survey (ECRHS III), who answered questions on physical activity at baseline (ECRHS II) and questions on physical activity, insomnia symptoms, sleep duration and daytime sleepiness at 10-year follow-up (ECRHS III). Participants who reported that they exercised with a frequency of at least two or more times a week, for 1 hour/week or more, were classified as being physically active. Changes in activity status were categorised into four groups: persistently non-active; became inactive; became active; and persistently active. MAIN OUTCOME MEASURES: Insomnia, sleep time and daytime sleepiness in relation to physical activity. RESULTS: Altogether, 37% of participants were persistently non-active, 25% were persistently active, 20% became inactive and 18% became active from baseline to follow-up. Participants who were persistently active were less likely to report difficulties initiating sleep (OR 0.60, 95% CI 0.45-0.78), a short sleep duration of ≤6 hours/night (OR 0.71, 95% CI 0.59-0.85) and a long sleep of ≥9 hours/night (OR 0.53, 95% CI 0.33-0.84) than persistently non-active subjects after adjusting for age, sex, body mass index, smoking history and study centre. Daytime sleepiness and difficulties maintaining sleep were not related to physical activity status. CONCLUSION: Physically active people have a lower risk of some insomnia symptoms and extreme sleep durations, both long and short.

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.

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.

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.

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.

The longitudinal association between physical activity, strength and fitness, and lung function: A UK Biobank cohort study.

BACKGROUND: While physical activity is hypothesized to slow lung-function decline, the evidence is limited at a population level. This study investigated the longitudinal association between physical activity and related measures (grip strength, cardiovascular fitness) and lung function decline. METHODS: 20,111 UK Biobank cohort participants with lung function measures at baseline (2006-2010) and follow-up (2012-2014) were included. Physical activity (International Physical Activity Questionnaire: low, moderate, high categories), grip strength (dynamometer) and cardiovascular fitness (subsample, submaximal stationary bicycle) data were collected. Linear regression was utilized to assess the effect on follow-up FEV1, FVC, FEV1/FVC ratio (as decline in ml/yr and as z-scores) adjusting for baseline lung function and confounders. RESULTS: After 6.3 years mean follow-up, the decline in mean FEV1 and FVC was 30 ml/year and 38 ml/year respectively (n = 20,111). Consistent low physical activity (across baseline and follow-up) was associated with accelerated decline in FEV1 z-score (-0.119, 95 % Confidence Interval (CI) -0.168, -0.071, n = 16,900) and FVC z-score (-0.133, 95%CI -0.178, -0.088, n = 16,832). Accelerated decline in FEV1 z-scores was observed with decreasing baseline grip strength (-0.029, -95%CI -0.034, -0.024, n = 19,903), and with less strong evidence, decreasing fitness (-0.024, 95%CI -0.070, 0.022, n = 3048). CONCLUSION: This is the largest ever study to date to identify that lower physical activity, grip strength, and potentially cardiovascular fitness over time is associated with accelerated lung function decline. Although the effect sizes appear modest, such changes at population levels can have a substantial overall impact. This study provides evidence for adding 'lung health benefits' to the current physical activity guidelines.

Longitudinal risk factors for obstructive sleep apnea: A systematic review.

Despite substantial disease burden, existing evidence on the risk factors for obstructive sleep apnea (OSA) have been derived primarily from cross-sectional studies without determining temporality. Therefore, we aimed to systematically synthesize the literature on longitudinal risk factors for sleep study-assessed OSA and questionnaire-assessed probable OSA from cohort studies in the general adult population settings. We systematically searched Embase and Medline (on OVID) databases. Eleven studies met the inclusion criteria. Meta-analyses were not conducted due to methodological heterogeneity of exposure and outcome measurements. There was consistent evidence that weight gain was associated with incident (n = 2) and greater severity (n = 2) of OSA. One study each observed an association of higher baseline body-mass index, male sex, asthma, a specific genetic polymorphism in rs12415421, and insulin resistance/hyperglycemia, with incident OSA. Long-term exposure to ambient air pollution (NO2, n = 1) was associated with OSA, and menopausal transitions (n = 1) with higher apnea-hypopnea index. There were no eligible studies on long-term smoking or alcohol use. In conclusion, approximately 10% increase in weight, especially in males, might alert clinicians to consider potential or worsening OSA. Large, well-designed longitudinal studies are needed to consolidate knowledge on other associations with OSA development, especially on potentially modifiable risk factors.

Life course BMI trajectories from childhood to mid-adulthood are differentially associated with anxiety and depression outcomes in middle age.

BACKGROUND/OBJECTIVE: Obesity is a risk factor for multimorbidity, including depression and possibly anxiety. However, it is currently unclear how patterns of change in BMI over the life course differentially influence the magnitude in risk of depression and anxiety in mid-adulthood. We aimed to examine associations between BMI trajectories from childhood to adulthood and the risk of depression and anxiety in middle age. METHODS: In the Tasmanian Longitudinal Health Study (n = 2416), five distinct BMI trajectories were previously defined from age 5 to 45 years using group-based modelling. At age 53, current depression and anxiety were assessed using the Patient Health Questionnaire and the Generalized Anxiety Disorder scale, respectively. Logistic regression models adjusted for potential confounders estimated associations between BMI trajectories and these outcomes. RESULTS: Those belonging to the child average-increasing (OR = 2.24; 95%CI: 1.24, 4.06) and persistently high (OR = 2.64; 1.26, 5.52) trajectories were more likely to have depression in middle age, compared to the persistently average trajectory. However, the odds of experiencing greater severity of depressive symptoms was highest in the child average-increasing group (OR = 2.36; 1.59, 3.49). Despite finding no evidence of association between BMI trajectories and current anxiety, we observed less severe symptoms in the child high-decreasing trajectory (OR = 0.68; 0.51, 0.91). CONCLUSION: We found an increased risk of depression in middle age among individuals with a persistently high BMI from childhood to mid-adulthood and individuals with an average BMI in childhood which then increased consistently throughout adulthood. Encouragingly, resolving childhood adiposity by adulthood was associated with lesser anxiety symptoms. Taken together, these findings highlight the need to target mental health screening and treatment towards high-risk BMI trajectory groups and the importance of early interventions to prevent and resolve excess weight.

Longitudinal Asthma Phenotypes from Childhood to Middle-Age: A Population-based Cohort Study.

Rationale: Asthma is a heterogeneous condition, and longitudinal phenotyping may provide new insights into the origins and outcomes of the disease. Objectives: We aimed to characterize the longitudinal phenotypes of asthma between the first and sixth decades of life in a population-based cohort study. Methods: Respiratory questionnaires were collected at seven time points in the TAHS (Tasmanian Longitudinal Health Study) when participants were aged 7, 13, 18, 32, 43, 50, and 53 years. Current-asthma and ever-asthma status was determined at each time point, and group-based trajectory modeling was used to characterize distinct longitudinal phenotypes. Linear and logistic regression models were fitted to investigate associations of the longitudinal phenotypes with childhood factors and adult outcomes. Measurements and Main Results: Of 8,583 original participants, 1,506 had reported ever asthma. Five longitudinal asthma phenotypes were identified: early-onset adolescent-remitting (40%), early-onset adult-remitting (11%), early-onset persistent (9%), late-onset remitting (13%), and late-onset persistent (27%). All phenotypes were associated with chronic obstructive pulmonary disease at age 53 years, except for late-onset remitting asthma (odds ratios: early-onset adolescent-remitting, 2.00 [95% confidence interval (CI), 1.13-3.56]; early-onset adult-remitting, 3.61 [95% CI, 1.30-10.02]; early-onset persistent, 8.73 [95% CI, 4.10-18.55]; and late-onset persistent, 6.69 [95% CI, 3.81-11.73]). Late-onset persistent asthma was associated with the greatest comorbidity at age 53 years, with increased risk of mental health disorders and cardiovascular risk factors. Conclusions: Five longitudinal asthma phenotypes were identified between the first and sixth decades of life, including two novel remitting phenotypes. We found differential effects of these phenotypes on risk of chronic obstructive pulmonary disease and nonrespiratory comorbidities in middle age.

The effect of early childhood respiratory infections and pneumonia on lifelong lung function: a systematic review.

Early childhood respiratory infections, including pneumonia, are an important global public health issue, with more than 40 million annual cases resulting in approximately 650 000 deaths. A growing number of published studies have examined the effects of early childhood lower respiratory tract infections (LRTIs) or pneumonia on lung function, particularly as part of large early-life exposure studies. To our knowledge, there is no published systematic review of these data. We searched PubMed, Embase, and Web of Science for studies published between database inception and May 12, 2022. Case-control, cohort, and cross-sectional studies were included if they reported forced expiratory volume in 1 s (FEV1) or forced vital capacity (FVC) values of participants older than 5 years. Article titles and abstracts were screened in Rayyan before retrieval, assessment, and data extraction of the full text. Primary outcome measures were differences in mean FEV1 or FVC values between exposed groups (ie, children aged ≤5 years with LRTIs) and non-exposed groups. This study is registered with PROSPERO, CRD42021265295. Database searches yielded 3070 articles, and 14 studies were included in this systematic review, providing a total of 23 276 participants, including 9969 children and 13 307 adults. Eight of 14 articles reported significant reductions in FEV1 values, and six of 12 studies reported reductions in FVC values in children and adults with a history of early childhood LRTIs or pneumonia, compared with unexposed controls (p<0·05). Most studies reporting reductions in lung function described deficits consistent with a restrictive spirometry pattern. Only two of 14 studies reported data from low-income and middle-income countries or disadvantaged populations in middle-income and high-income countries, and there were scarce data available on the effect of LRTI severity and recurrence on lung function. LRTIs in early childhood could be associated with a restrictive spirometry pattern in later childhood and adulthood. Data are needed from low-income and middle-income nations, and from disadvantaged populations in middle-income and high-income countries in which early childhood respiratory infection burden is disproportionately high. Data are also needed on the effect of LRTI severity and recurrence on future lung function.

Epidemiology of eczema in South-Eastern Australia.

BACKGROUND/OBJECTIVES: Eczema is a common chronic debilitating skin condition in childhood. Data on the epidemiology and natural history of eczema across the life course are lacking. This analysis aimed to describe these epidemiological features in Australian children and adults. METHODS: Data collected on eczema from four Australian cohort studies were analysed: namely HealthNuts, Melbourne Atopic Cohort Study (MACS), Tasmanian Longitudinal Health Study (TAHS) and the Australian arm of the European Community Respiratory Health Survey (ECRHS). RESULTS: Among children aged under 6 years, 28.8%-35.6% have ever-had eczema, and 16.7%-26.6% had 'current eczema'. Among those aged 6-12 years, 14.6%-24.7% had 'current eczema' with 12.0%-18.5% of those at ages of 6 and 10 years classified as having moderate-to-severe eczema according to the Scoring of Atopic Dermatitis (SCORAD) index. In adults, the prevalence of 'eczema ever' ranged between 13.8% and 48.4%. The 12-month period prevalence of eczema was 15.1% at age 18, while current eczema was 8.5% at an average age of 51, and 8.8% at an average age 53 years. Eczema was more common among young boys, but this difference became non-significant for older children and early adolescents. In contrast, eczema was more common for adult women than men. CONCLUSIONS: Eczema is common both in children and adults. The proportion of severe eczema in children was substantial.

Biomarkers of asthma relapse and lung function decline in adults with spontaneous asthma remission: A population-based cohort study.

BACKGROUND: The extent to which biomarkers of asthma activity persist in spontaneous asthma remission and whether such markers are associated with future respiratory outcomes remained unclear. We investigated the association between sub-clinical inflammation in adults with spontaneous asthma remission and future asthma relapse and lung function decline. METHODS: The Tasmanian Longitudinal Health Study is a population-based cohort (n = 8583). Biomarkers of systemic inflammation were measured on participants at age 45, and latent profile analysis was used to identify cytokine profiles. Bronchial hyperresponsiveness (BHR) and nitric oxide products in exhaled breath condensate (EBC NOx) were measured at age 50. Participants with spontaneous asthma remission at ages 45 (n = 466) and 50 (n = 318) were re-evaluated at age 53, and associations between baseline inflammatory biomarkers and subsequent asthma relapse and lung function decline were assessed. RESULTS: We identified three cytokine profiles in adults with spontaneous asthma remission: average (34%), Th2-high (42%) and Th2-low (24%). Compared to the average profile, a Th2-high profile was associated with accelerated decline in post-BD FEV1 /FVC (MD -0.18% predicted per-year; 95% CI -0.33, -0.02), while a Th2-low profile was associated with accelerated decline in both post-BD FEV1 (-0.41%; -0.75, -0.06) and post-BD FVC (-0.31%; -0.62, 0.01). BHR and high TNF-α during spontaneous remission were associated with an increased risk of asthma relapse. In contrast, we found no evidence of association between EBC NOx and either asthma relapse or lung function decline. CONCLUSION: BHR and serum inflammatory cytokines have prognostic value in adults with spontaneous asthma remission. At-risk individuals with BHR, Th2-high or Th2-low cytokine profiles may benefit from closer monitoring and on-going follow-up.

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.