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

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 (FEV₁1)/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

Primary and secondary hepatic lymphomas diagnosed by image-guided fine-needle aspiration : a retrospective study of clincal 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

Primary and secondary hepatic lymphomas diagnosed by image-guided fine-needle aspiration : a retrospective study of clincal 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

Primary and secondary hepatic lymphomas diagnosed by image-guided fine-needle aspiration : a retrospective study of clincal 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

Identification of Asthma Subtypes Using Clustering Methodologies

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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

Trajectories of restrictive pattern of lung function FEV1/FVC to physiological peak and their relationship with early life risk-factors and cardiac markers

Objectives: lung function in early adulthood is an important determinant of all-cause mortality and COPD. We aimed to model data from multiple cohorts from pre-school age to physiological peak in early adulthood to derive FEV1/FVC trajectories. We then investigated the association of the derived trajectories with early-life risk factors and markers of cardiovascular risk in adulthood.Method: using latent profile modelling, we studied three population-based birth cohorts (ALSPAC, MAAS, IOW) with repeat spirometry data from childhood into early adulthood to identify trajectories of FEV1/FVC. We performed echocardiogram and measured seated systolic blood pressure in ~3200 participants in ALSPAC at age 24 years. 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 later adulthood.Results: we identified four distinct FEV1/FVC ratio trajectories with strikingly similar latent profiles in three independent birth cohorts: Above average (49.5%); Average (38.3%); Below average (10.6%); and Persistently low (1.7%). Male gender and history of allergic symptoms (wheeze, cough, asthma and sensitization) were significant associates of diminished lung function trajectories in all cohorts. We found strong evidence of the increase in cardiovascular risk markers ascertained by echocardiography (including left ventricular mass indexed to height and carotid intima-media thickness) with decreasing FEV1/FVC trajectory (with p-values for the mean effects per trajectory ranging from 0.005 to 11.17×10−7). The average seated systolic blood pressure (mm Hg) increased significantly per decreasing FEV1/FVC trajectory (p = 2.8×10−9)Conclusions: childhood lung function trajectories may serve as important predictors in the development of not only future lung disease, but also the cardiovascular disease and multimorbidity in adulthood. Our findings highlight the importance of measuring lung function throughout childhood and early adulthood