Pulmonary vasculature and critical asthma syndromes: a comprehensive review.

One of the important factors and consequences in persistent asthma is the change in the vasculature of the airways and lung parenchyma. These changes could contribute to worsening asthma control and predispose asthmatics to critical asthma syndromes. For many years, the contribution of vasculature to severe asthma was limited to discussion of small and medium vessel vasculitis commonly referred to as Churg-Strauss syndrome. This comprehensive review will explore the known mechanisms that are associated with remodeling of the vasculature in a variety of critical asthma presentations. Inflammation of pulmonary and bronchial small blood vessels may contribute significantly but silently to asthma pathobiology. Inflammation in the vasculature of the lung parenchyma can decrease lung capacity while inflammation in airway vasculature can decrease airflow. This review will provide a modern perspective on Churg-Strauss syndromes with a focus on phenotyping, mechanism, and ultimately modern therapeutic approaches. Vascular remodeling and airway remodeling are not mutually exclusive concepts in understanding the progression of asthma and frequency of acute exacerbations. Furthermore, the contribution of vascular leak, particularly in the parenchymal vasculature, has become an increasingly recognized component of certain presentations of poorly controlled, severe persistent asthmatic and during exacerbations. We highlight how these mechanisms can contribute to some the severe presentations of influenza infection in patients with a history of asthma. The ultimate aim of this review is to summarize the current literature concerning vasculitis and the contribution of airway and parenchymal vascular remodeling to presentation of persistent asthma and its consequences during acute exacerbations and critical asthma syndromes

Paradigms in chronic obstructive pulmonary disease: phenotypes, immunobiology, and therapy with a focus on vascular disease.

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous syndrome that represents a major global health burden. COPD phenotypes have recently emerged based on large cohort studies addressing the need to better characterize the syndrome. Though comprehensive phenotyping is still at an early stage, factors such as ethnicity and radiographic, serum, and exhaled breath biomarkers have shown promise. COPD is also an immunological disease where innate and adaptive immune responses to the environment and tobacco smoke are altered. The frequent overlap between COPD and other systemic diseases, such as cardiovascular disease, has influenced COPD therapy, and treatments for both conditions may lead to improved patient outcomes. Here, we discuss current paradigms that center on improving the definition of COPD, understanding the immunological overlap between COPD and vascular inflammation, and the treatment of COPD-with a focus on comorbid cardiovascular disease

Health System Implementation of a Tobacco Quitline eReferral.

BACKGROUND:Proactive referrals through electronic orders (eReferrals) can increase patient connection with tobacco quitlines. More information is needed on "real-world" implementation of electronic health record tools to promote tobacco cessation while minimizing provider burden. OBJECTIVES:This paper examines the health system implementation of an eReferral to a tobacco quitline without best practice alerts in primary care, specialty, and hospital settings in an academic health system. METHODS:This is a prospective implementation study of a health system tobacco eReferral to a state quitline that was completed with an approach to minimize provider cognitive burden. Data are drawn from electronic health record data at University of California, Davis Health Systems (March 2013-February 2016). RESULTS:Over 3 years, 16,083 encounters with smokers resulted in 1,137 eReferral orders (7.1%). Treatment reach was 1.6% for quitline services and 2.3% for outpatient group classes. While the group classes were offered to outpatient smokers, the eReferral order was included in an outpatient order set and eventually an automated inpatient discharge order set; no provider alerts were implemented. Referrals were sustained and doubled after inpatient order set implementation. Among all first time eReferral patients, 12.2% had a 6 to 12 month follow-up visit at which they were documented as nonsmoking. CONCLUSION:This study demonstrates a quitline eReferral order can be successfully implemented and sustained with minimal promotion, without provider alerts and in conjunction with group classes. Reach and effectiveness were similar to previously described literature

SMAD Signaling in the Airways of Healthy Rhesus Macaques versus Rhesus Macaques with Asthma Highlights a Relationship Between Inflammation and Bone Morphogenetic Proteins

Bone morphogenetic protein (BMP) signaling is important for correct lung morphogenesis, and there is evidence of BMP signaling reactivation in lung diseases. However, little is known about BMP signaling patterns in healthy airway homeostasis and inflammatory airway disease and during epithelial repair. In this study, a rhesus macaque (Macaca mulatta) model of allergic airway disease was used to investigate BMP signaling throughout the airways in health, disease, and regeneration. Stereologic quantification of immunofluorescent images was used to determine the expression of BMP receptor (BMPR) Ia and phosphorylated SMAD (pSMAD) 1/5/8 in the airway epithelium. A pSMAD 1/5/8 expression gradient was found along the airways of healthy juvenile rhesus macaques (n = 3, P , 0.005). Membrane-localized BMPRIa expression was also present in the epithelium of the healthy animals. After exposure to house dust mite allergen and ozone, significant down-regulation of nuclear pSMAD 1/5/8 occurs in the epithelium. When the animals were provided with a recovery period in filtered air, proliferating cell nuclear antigen, pSMAD 1/5/8, and membrane-localized BMPRIa expression were significantly increased in the epithelium of conducting airways (P , 0.005). Furthermore, in the asthmatic airways, altered BMPRIa localization was evident. Because of the elevated eosinophil presence in these airways, we investigated the effect of eosinophil-derived proteins on BMPRIa trafficking in epithelial cells. Eosinophil-derived proteins (eosinophil-derived neurotoxin, eosinophil peroxidase, and major basic protein) induced transient nuclear translocation of membrane-bound BMPRIa. This work mapping SMAD signaling in the airways of nonhuman primates highlights a potential mechanistic relationship between inflammatory mediators and BMP signaling and provides evidence that basal expression of the BMP signaling pathway may be important for maintaining healthy airways

Vascular Remodeling Is Airway Generation-Specific in a Primate Model of Chronic Asthma

Rationale: Changes in the density of bronchial vessels have been proposed as a part of airway remodeling that occurs in chronic asthma

Disability and Recovery of Independent Function in Obstructive Lung Disease: The Cardiovascular Health Study

BACKGROUND: Chronic obstructive lung disease frequently leads to disability. Older patients may transition between disability and independence over time. OBJECTIVE: To identify factors associated with transitions between disability and independent function in obstructive lung disease. METHODS: We analyzed data for 4,394 participants in the Cardiovascular Health Study who completed pre-bronchodilator spirometry. We calculated the 1-year probability of developing and resolving impairment in ≥1 Instrumental Activity of Daily Living (IADL) or ≥1 Activity of Daily Living (ADL) using transition probability analysis. We identified factors associated with resolving disability using relative risk regression. RESULTS: The prevalence of IADL impairment was higher among moderate (23.9%) and severe (36.9%) airflow obstruction compared to normal spirometry (22.5%; p<0.001). Among participants with severe airflow obstruction, 23.5% recovered independence in IADLs and 40.5% recovered independence in ADLs. In adjusted analyses, airflow obstruction predicted development of IADL, but not ADL impairment. Participants with severe airflow obstruction were less likely to resolve IADL impairment (RR 0.67, 95% CI 0.49-0.94). Compared to the most active persons (≥28 blocks walked per week), walking less was associated with decreased likelihood of resolving IADL impairment (7-27 blocks: RR 0.81, 0.69-0.86, and < 7 blocks: RR 0.73, 0.61 -0.86). Increased strength (RR 1.16, 1.05-1.29) was associated with resolving IADL impairment. CONCLUSIONS: Disability is common in older persons, especially those with severe airflow obstruction. Increased physical activity and muscle strength are associated with recovery. Research on interventions to improve these factors among patients with obstructive lung disease and disability is needed