The chitinase-like protein YKL-40 mediates airway inflammation, and serum levels are associated with asthma severity. However, asthma phenotypes associated with YKL-40 levels have not been precisely defined. We conducted an unsupervised cluster analysis of asthma patients treated at the Yale Center for Asthma and Airways Disease (YCAAD, n=156) to identify subgroups according to YKL-40 level. The resulting YKL-40 clusters were cross-validated in cohorts from the Severe Asthma Research Program (SARP) (n=167) and the New York University Bellevue Asthma Repository (NYUBAR) (n=341). A sputum transcriptome analysis revealed molecular pathways associated with YKL-40 subgroups. Four YKL-40 clusters (C1-4) were identified. C3 and C4 had high serum YKL-40 levels compared to C1 and C2. C3 was associated with earlier onset and longer duration of disease, severe airflow obstruction and near-fatal asthma exacerbations. C4 had the highest serum YKL-40 levels, adult onset, and less airflow obstruction but frequent exacerbations. An airway transcriptome analysis in C3 and C4 showed activation of non-Type 2 inflammatory pathways. Elevated serum YKL-40 levels were associated with two distinct clinical asthma phenotypes: one with irreversible airway obstruction and another with severe exacerbations. The YKL-40 clusters are potentially useful for identification of individuals with severe or exacerbation-prone asthma.

Body dysmorphic disorder (BDD) is a disabling illness with a high worldwide prevalence. Patients demonstrate a debilitating preoccupation with one or more perceived defects, often marked by poor insight or delusional convictions. Multiple studies have suggested that selective serotonin reuptake inhibitors and various cognitive behavioral therapy modalities are effective first-line treatments in decreasing BDD severity, relieving depressive symptoms, restoring insight, and increasing quality of life. Selective serotonin reuptake inhibitors have also recently been shown to be effective for relapse prevention. This review provides a comprehensive summary of the current understanding of BDD, including its clinical features, epidemiology, genetics, and current treatment modalities. Additional research is needed to fully elucidate the relationship between BDD and comorbid illnesses such as obsessive–compulsive-related disorders and depression and to develop therapies for refractory patients and those who have contraindications for pharmacological intervention.

Body dysmorphic disorder is a challenging disorder that manifests as erroneously perceived flaws in one's physical appearance and repetitive behaviors in response to appearance concerns. This disorder is also frequently comorbid with other psychiatric disorders, including major depressive disorder and autism spectrum disorder. It is currently understood to arise from a combination of biological, psychological, and environmental factors. Treatment of body dysmorphic disorder typically consists of a combination of pharmacotherapy and cognitive behavioral therapy. However, not all patients respond to treatment, and BDD symptoms remain even in those who do respond. This review outlines current pharmacological and neuromodulation treatments for body dysmorphic disorder, and suggests directions for future studies of novel treatments such as augmentation with atypical antipsychotics and the use of intranasal oxytocin in cases of body dysmorphic disorder that show residual symptomatology even with tailored monotherapy. There is emerging evidence suggesting that non-invasive neurostimulatory techniques, such as repetitive transcranial magnetic stimulation, may be of value in treatment-resistant cases.

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