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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

BACKGROUND: In a population-based sample of school-age children, we investigated factors associated with rhinitis, and differences between allergic and nonallergic rhinitis. Amongst children with asthma, we explored the association between rhinitis and asthma severity. METHODS: Children participating in a birth cohort study (n = 906) were reviewed at age 8 years. Asthma was defined as at least two of the following three features: physician-diagnosed asthma, currently using asthma medication and current wheeze. We measured lung function (plethysmography and spirometry) and airway hyper-reactivity (AHR; methacholine challenge). RESULTS: In the analysis adjusted for the presence of asthma, children with rhinitis had significantly higher AHR (P = 0.001). Maternal smoking and absence of breastfeeding were stronger predictors of nonallergic rhinitis, whereas current wheeze and eczema were stronger predictors of allergic rhinitis. Amongst asthmatics (n = 159), when compared to 76 children without rhinitis, those with rhinitis (n = 83) were 2.89-fold (95% CI 1.41-5.91) more likely to experience frequent attacks of wheezing, 3.44-fold (1.19-9.94) more likely to experience severe attacks of wheezing limiting speech, 10.14-fold (1.27-81.21) more likely to have frequent visits to their doctor because of asthma and nine-fold (1.11-72.83) more likely to miss school. Reported use of intranasal corticosteroids resulted in a numerically small, but consistent reduction in risk, rendering the associations between rhinitis and asthma severity nonsignificant. CONCLUSION: We observed differences in risk factors and severity between allergic and nonallergic rhinitis. In children with asthma, rhinitis had adverse impact on asthma severity. The use of intranasal corticosteroids resulted in a small, but consistent reduction in the risk.

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.

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.

Methods Subjects were recruited prenatally and followed prospectively, attending follow-up at ages 3, 5, 8, and 11 years. A validated questionnaire was interviewer-administered to collect information on parentally-reported symptoms (n=1051). At each follow-up, current rhinitis was defined as sneezing, runny or blocked nose in the absence of cold or flu within the last 12 months, and asthma as a positive response to at least two of the following: 1) current wheeze; 2) physician-diagnosed asthma; 3) use of asthma medication. We measured specific airway resistance (sRaw) using plethysmography (ages 5-11 years) and FEV1 by spirometry (5, 8 and 11). Information on prescribed medication and severe asthma exacerbations (ATS definition) was extracted from participants’ medical records. The effect of rhinitis on asthma exacerbations and lung function was investigated using longitudinal analyses.

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.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.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).Image-guided FNA with immediate evaluation is a reliable means to obtain diagnostic material and triage for ancillary tests.

Introduction The use of unsupervised clustering has identified different subtypes of asthma. Choosing the variables to input into the clustering algorithm is one of the important considerations. The majority of previous studies selected variables based on expert advice, whilst others used dimension reduction techniques such as principal component analysis (PCA). We aimed to compare the results of unsupervised clustering when using raw variables, or variables transformed using dimensionality reduction techniques. Methods We performed our analysis on 613 asthmatics aged 6–23 years from Ankara, Turkey. We conducted extensive phenotyping and recorded 49 variables including demographic data, sensitisation, lung function, medication, peripheral eosinophilia, and markers of asthma severity. We performed hierarchical clustering (HC) using: (1) all variables; and (2) variables transformed using dimensionality reduction techniques. Results PCA revealed 5 components describing atopy and variations in asthma severity, which were then used to infer cluster assignment. The optimal HC solution in both PCA-transformed and raw untransformed data identified five clusters. However, these clusters were not identical. Both identified mild asthma with good lung function, severe atopic asthma and late-onset mild atopic asthma. However, the overlap between children assigned to these three clusters in two HC analyses was modest. Clustering without PCA identified early-onset severe atopic asthma and late-onset atopic asthma with high BMI, whilst early onset non-atopic mild asthma in females was identified in HC with PCA. Using both methods, we identified four features that characterised the clusters. These were age of onset, atopy, asthma attacks, and asthma severity. Using only these four features, we identified early onset atopic mild asthma, early onset non-atopic mild asthma, severe asthma, late onset asthma, and exacerbation prone asthma. Cluster stability increased drastically. Conclusion Different methodologies applied to the same dataset identified differing clusters of asthma. We identified four features that characterised the clusters. We propose that these four features could be more useful in identifying asthma endotypes.

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.