Lung function trajectories from school age to adulthood and their relationship with markers of cardiovascular disease risk.

RATIONALE: Lung function in early adulthood is associated with subsequent adverse health outcomes. OBJECTIVES: To ascertain whether stable and reproducible lung function trajectories can be derived in different populations and investigate their association with objective measures of cardiovascular structure and function. METHODS: Using latent profile modelling, we studied three population-based birth cohorts with repeat spirometry data from childhood into early adulthood to identify trajectories of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC). We used multinomial logistic regression models to investigate early-life predictors of the derived trajectories. We then ascertained the extent of the association between the derived FEV1/FVC trajectories and blood pressure and echocardiographic markers of increased cardiovascular risk and stroke in ~3200 participants at age 24 years in one of our cohorts. RESULTS: We identified four FEV1/FVC trajectories with strikingly similar latent profiles across cohorts (pooled N=6377): above average (49.5%); average (38.3%); below average (10.6%); and persistently low (1.7%). Male sex, wheeze, asthma diagnosis/medication and allergic sensitisation were associated with trajectories with diminished lung function in all cohorts. We found evidence of an increase in cardiovascular risk markers ascertained by echocardiography (including left ventricular mass indexed to height and carotid intima-media thickness) with decreasing FEV1/FVC (with p values for the mean crude effects per-trajectory ranging from 0.10 to p<0.001). In this analysis, we considered trajectories as a pseudo-continuous variable; we confirmed the assumption of linearity in all the regression models. CONCLUSIONS: Childhood lung function trajectories may serve as predictors in the development of not only future lung disease, but also the cardiovascular disease and multimorbidity in adulthood.

Longitudinal trajectories of severe wheeze exacerbations from infancy to school age and their association with early-life risk factors and late asthma outcomes.

INTRODUCTION: Exacerbation-prone asthma subtype has been reported in studies using data-driven methodologies. However, patterns of severe exacerbations have not been studied. OBJECTIVE: To investigate longitudinal trajectories of severe wheeze exacerbations from infancy to school age. METHODS: We applied longitudinal k-means clustering to derive exacerbation trajectories among 887 participants from a population-based birth cohort with severe wheeze exacerbations confirmed in healthcare records. We examined early-life risk factors of the derived trajectories, and their asthma-related outcomes and lung function in adolescence. RESULTS: 498/887 children (56%) had physician-confirmed wheeze by age 8 years, of whom 160 had at least one severe exacerbation. A two-cluster model provided the optimal solution for severe exacerbation trajectories among these 160 children: "Infrequent exacerbations (IE)" (n = 150, 93.7%) and "Early-onset frequent exacerbations (FE)" (n = 10, 6.3%). Shorter duration of breastfeeding was the strongest early-life risk factor for FE (weeks, median [IQR]: FE, 0 [0-1.75] vs. IE, 6 [0-20], P < .001). Specific airway resistance (sRaw ) was significantly higher in FE compared with IE trajectory throughout childhood. We then compared children in the two exacerbation trajectories with those who have never wheezed (NW, n = 389) or have wheezed but had no severe exacerbations (WNE, n = 338). At age 8 years, FEV1 /FVC was significantly lower and FeNO significantly higher among FE children compared with all other groups. By adolescence (age 16), subjects in FE trajectory were significantly more likely to have current asthma (67% FE vs. 30% IE vs. 13% WNE, P < .001) and use inhaled corticosteroids (77% FE vs. 15% IE vs. 18% WNE, P < .001). Lung function was significantly diminished in the FE trajectory (FEV1 /FVC, mean [95%CI]: 89.9% [89.3-90.5] vs. 88.1% [87.3-88.8] vs. 85.1% [83.4-86.7] vs. 74.7% [61.5-87.8], NW, WNE, IE, FE respectively, P < .001). CONCLUSION: We have identified two distinct trajectories of severe exacerbations during childhood with different early-life risk factors and asthma-related outcomes in adolescence.

Asthma phenotypes in childhood.

INTRODUCTION: Asthma is no longer thought of as a single disease, but rather a collection of varying symptoms expressing different disease patterns. One of the ongoing challenges is understanding the underlying pathophysiological mechanisms that may be responsible for the varying responses to treatment. Areas Covered: This review provides an overview of our current understanding of the asthma phenotype concept in childhood and describes key findings from both conventional and data-driven methods. Expert Commentary: With the vast amounts of data generated from cohorts, there is hope that we can elucidate distinct pathophysiological mechanisms, or endotypes. In return, this would lead to better patient stratification and disease management, thereby providing true personalised medicine.

Identification of Asthma Subtypes Using Clustering Methodologies.

Asthma is a heterogeneous disease comprising a number of subtypes which may be caused by different pathophysiologic mechanisms (sometimes referred to as endotypes) but may share similar observed characteristics (phenotypes). The use of unsupervised clustering in adult and paediatric populations has identified subtypes of asthma based on observable characteristics such as symptoms, lung function, atopy, eosinophilia, obesity, and age of onset. Here we describe different clustering methods and demonstrate their contributions to our understanding of the spectrum of asthma syndrome. Precise identification of asthma subtypes and their pathophysiological mechanisms may lead to stratification of patients, thus enabling more precise therapeutic and prevention approaches.

Primary and secondary hepatic lymphomas diagnosed by image-guided fine-needle aspiration: a retrospective study of clinical and cytomorphologic findings.

OBJECTIVES: To explore the diagnosis of hematolymphoid malignancies of the liver (hepatic lymphoma [HeL]) by image-guided fine-needle aspiration (FNA), which can often be difficult due to a low index of suspicion and nonspecific patient presentations, especially in the rare cases where the liver is the only site of disease (primary HeL [PHeL]). Understanding the clinical setting in which such lesions arise, as well as the cytomorphologic findings, may assist cytopathologists in making an accurate diagnosis and triaging samples for ancillary studies. METHODS: In this retrospective study of 32 patients with HeL, the largest such study to our knowledge, we review the clinical and diagnostic features of HeL. RESULTS: HeL and especially PHeL most commonly show a diffuse large B-cell lymphoma phenotype and have a poor prognosis (median survival of seven months). PHeL is strongly associated with human immunodeficiency virus infection (12/16 patients). CONCLUSIONS: Image-guided FNA with immediate evaluation is a reliable means to obtain diagnostic material and triage for ancillary tests.