COPD is a heterogeneous syndrome. Many COPD subtypes have been proposed, but there is not yet consensus on how many COPD subtypes there are and how they should be defined. The COPD Genetic Epidemiology Study (COPDGene), which has generated 10-year longitudinal chest imaging, spirometry, and molecular data, is a rich resource for relating COPD phenotypes to underlying genetic and molecular mechanisms. In this article, we place COPDGene clustering studies in context with other highly cited COPD clustering studies, and summarize the main COPD subtype findings from COPDGene. First, most manifestations of COPD occur along a continuum, which explains why continuous aspects of COPD or disease axes may be more accurate and reproducible than subtypes identified through clustering methods. Second, continuous COPD-related measures can be used to create subgroups through the use of predictive models to define cut-points, and we review COPDGene research on blood eosinophil count thresholds as a specific example. Third, COPD phenotypes identified or prioritized through machine learning methods have led to novel biological discoveries, including novel emphysema genetic risk variants and systemic inflammatory subtypes of COPD. Fourth, trajectory-based COPD subtyping captures differences in the longitudinal evolution of COPD, addressing a major limitation of clustering analyses that are confounded by disease severity. Ongoing longitudinal characterization of subjects in COPDGene will provide useful insights about the relationship between lung imaging parameters, molecular markers, and COPD progression that will enable the identification of subtypes based on underlying disease processes and distinct patterns of disease progression, with the potential to improve the clinical relevance and reproducibility of COPD subtypes.

The differential risk of pneumonia among inhaled corticosteroid (ICS) use in patients with COPD requires more investigation, especially regarding beclomethasone-containing inhalers. The goal of this study was to compare the risk and benefit profile of different ICS/long-acting β2-agonist (LABA) combinations in patients with COPD.

The etiology of idiopathic pulmonary fibrosis (IPF) is unknown. Because it shares genetic, histopathologic, and radiographic features with the fibrosing interstitial lung disease seen in rheumatoid arthritis (RA), the goal of this study was to investigate RA-related autoantibodies in IPF.

Sleep is important to health and well-being, and studies in healthy adults have demonstrated that sleep deprivation impacts respiratory, immune, and cognitive function. Historically, because of the nature of critical illness, sleep has not been considered a priority for patient care in the ICU. More recently, research has demonstrated that sleep is markedly abnormal in patients who are critically ill. In addition, there is often disruption of circadian rhythms. Delirium is a syndrome of acute alteration in mental status that occurs in the setting of contributing factors such as serious illness, medication, and drug or alcohol intoxication or withdrawal. Delirium is a frequent occurrence in critical illness, and research has demonstrated several adverse outcomes associated with delirium including persistent cognitive impairment and increased mortality. Sleep deprivation and delirium share many common symptoms. The similarity in symptoms between sleep disruption and delirium have prompted experts to draw links between the two and question both the relationship and its direction. In addition, the inclusion of sleep disturbance to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition in its constellation of symptoms used in diagnosing delirium has increased awareness of the link between sleep and delirium. This paper will review the literature on sleep in critical illness and the potential mechanisms and pathways that may connect sleep and delirium.