Longitudinal trajectories of asthma exacerbations from infancy to school age.

Introduction Previous studies which used data-driven methodologies have reported the existence of an exacerbation-prone asthma subtype, which is independent of asthma severity. However, longitudinal patterns of asthma exacerbations during childhood have not been studied. Objectives and Approach We sought to investigate whether there are distinct longitudinal trajectories of asthma exacerbations from infancy to school-age that could facilitate better understanding of the heterogeneity of asthma syndrome. We used longitudinal k-means modelling (an unsupervised data-driven method), to analyse linked primary care data from 916 participants in a population-based birth cohort study (Manchester Asthma and Allergy Study), to ascertain clusters of children with similar trajectories of asthma exacerbations during childhood (n=160). We tested the validity of these clusters in relation to lung function, airway hyperreactivity and inflammation, allergic sensitisation, and the use of asthma medication. Results A two-cluster model provided the optimal solution for our data set. Based on the pattern of exacerbations from infancy to age 8 years, we assigned the clusters as: “Early-onset frequent exacerbations (FE)” (n=10) and “Infrequent exacerbations (IE)” (n=150). Shorter duration of breastfeeding was the strongest risk factor for FE (median weeks 0 (IQR: 0-1.75) vs IE, median weeks 6 (IQR: 0-20), p<0.001). Children in the FE cluster were more likely to exhibit persistent wheeze (90% vs 47%, p=0.03) and have poorer lung function, more airway hyperreactivity, and more airway inflammation throughout childhood (Table 1). In a post-hoc analysis, when we compared children in the exacerbation clusters with those who have wheezed only (n=389), and those that wheezed but had no exacerbations (n=338), other early life risk factors such as atopic sensitisation (IE - RR: 3.2 (95%CI: 2.1-5.1), p<0.001) (FE - RR: 10.9 (95%CI: 2.1-57.7), p=0.004), exposure to tobacco smoke at birth (FE - RR: 2.8 (95%CI: 1.3-6.3) ,p=0.02), position in sibship (IE - RR: 1.5 (95%CI: 1.0-2.3), p=0.03), and day care attendance (IE - RR:0.6 (95%CI: 0.4-0.9), p=0.01) were significantly associated with exacerbations. Conclusion/Implications We have identified two distinct patterns of asthma exacerbations during childhood with different outcomes, early-life risk factors, and lung function when compared to children who wheeze, but have no exacerbations. These results indicate that exacerbations represent an independent susceptibility phenotype

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&lt;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

<p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s41030-016-0017-z">https://link.springer.com/article/10.1007/s41030-016-0017-z</a></p><p></p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p

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