Chest
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Pulmonary arterial hypertension (PAH) is a rare disease associated with abnormally elevated pulmonary pressures and right heart failure resulting in high morbidity and mortality. Although the prognosis for patients with PAH has improved with the introduction of pulmonary vasodilators, disease progression remains a major problem. Given that available therapies are inadequate for preventing small-vessel loss and obstruction, there is active interest in identifying drugs capable of targeting angiogenesis and mechanisms involved in the regulation of cell growth and fibrosis. ⋯ These drugs target seven of the major mechanisms associated with PAH pathogenesis: bone morphogenetic protein signaling, tyrosine kinase receptors, estrogen metabolism, extracellular matrix, angiogenesis, epigenetics, and serotonin metabolism. In this review, we discuss the preclinical studies that led to prioritization of these mechanisms, and discuss completed and ongoing phase 2/3 trials using novel interventions such as sotatercept, anastrozole, rodatristat ethyl, tyrosine kinase inhibitors, and endothelial progenitor cells, among others. We anticipate that the next generation of compounds will build on the success of the current standard of care and improve clinical outcomes and quality of life for patients with PAH.
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The Confusion, Urea > 7 mM, Respiratory Rate ≥ 30 breaths/min, BP < 90 mm Hg (Systolic) or < 60 mm Hg (Diastolic), Age ≥ 65 Years (CURB-65) score and the Pneumonia Severity Index (PSI) are well-established clinical prediction rules for predicting mortality in patients hospitalized with community-acquired pneumonia (CAP). SARS-CoV-2 has emerged as a new etiologic agent for CAP, but the role of CURB-65 score and PSI have not been established. ⋯ PSI and CURB-65 score can predict in-hospital mortality for patients with SARS-CoV-2 CAP and non-SARS-CoV-2 CAP comparatively. In patients with SARS-CoV-2 CAP, the inclusion of either D-dimer or procalcitonin to PSI or CURB-65 score did not improve the prognostic performance of either score. In patients with CAP, regardless of cause, PSI and CURB-65 score remain adequate for predicting mortality in clinical practice.
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Multiparametric risk assessment is used in pulmonary arterial hypertension (PAH) to target therapy. However, this strategy is imperfect because most patients remain at intermediate or high risk after initial treatment, with low risk being the goal. Metrics of right ventricular (RV) adaptation are promising tools that may help refine our therapeutic strategy. ⋯ In patients with advanced PAH, RV-pulmonary arterial coupling could not discriminate irreversible RV failure (nonresponders) at presentation but showed a late trend to improvement by follow-up 2. Early change in Eed and baseline RV ejection fraction were the best predictors of therapeutic response.
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Lung cancer ranks second for cancer incidence and first for cancer mortality. Investigation into its risk factors and epidemiologic trends could help describe geographical distribution and identify high-risk population groups. ⋯ Most countries had increasing trends in females but decreasing trends in males and in lung cancer incidence and mortality. Tobacco related measures and early cancer detection should be implemented to control the increasing trends of lung cancer in females, and in regions identified as having these trends. Future studies may explore the reasons behind these epidemiological transitions.
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Although guidelines long have recommended objective pulmonary function testing to diagnose asthma and COPD, many primary care patients receive a clinical diagnosis of asthma or COPD without objective testing. This often leads to unnecessary treatment with associated incremental costs and side effects and delays actual diagnosis. ⋯ Barriers to objective testing for airway disease in primary care are complex and span many theoretical domains. Correspondingly, a successful intervention must leverage multiple behavior change techniques. A theory-based, multifaceted intervention to address underuse of diagnostic testing for asthma or COPD now should be developed and tested.