Proceedings of the American Thoracic Society
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Chronic obstructive pulmonary disease (COPD) has been a major public health problem during the 20th century, and will remain a challenge for the foreseeable future. Worldwide, COPD is in the spotlight, because its high prevalence, morbidity, and mortality create formidable challenges for healthcare systems. However, there remain many ongoing, contentious issues in COPD, including the definition and staging of COPD itself. ⋯ Cigarette smoking is the principal causal factor, but other factors play a role in causing and triggering COPD. Likely, the clinical presentation of COPD and its contributing phenotypes within the remainder of the 21st century will be different than the "blue bloaters" and "pink puffers" observed one or two generations ago. Hopefully, the COPD clinical course will shift to better outcomes and prognosis than in the past.
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During the past 30 years, major advances have been made in our understanding of HIV/AIDS and Pneumocystis pneumonia (PCP), but significant gaps remain. Pneumocystis is classified as a fungus and is host-species specific, but an understanding of its reservoir, mode of transmission, and pathogenesis is incomplete. PCP remains a frequent AIDS-defining diagnosis and is a frequent opportunistic pneumonia in the United States and in Europe, but comparable epidemiologic data from other areas of the world that are burdened with HIV/AIDS are limited. ⋯ Trimethoprim-sulfamethoxazole is the recommended first-line treatment and prophylaxis regimen, but putative trimethoprim-sulfamethoxazole drug resistance is an emerging concern. The International HIV-associated Opportunistic Pneumonias (IHOP) study was established to address these knowledge gaps. This review describes recent advances in the pathogenesis, epidemiology, diagnosis, and management of HIV-associated PCP and ongoing areas of clinical and translational research that are part of the IHOP study and the Longitudinal Studies of HIV-associated Lung Infections and Complications (Lung HIV).
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As HIV-infected persons on combination antiretroviral therapy (ART) are living longer and rates of opportunistic infections have declined, serious non-AIDS-related diseases account for an increasing proportion of deaths. Consistent with these changes, non-AIDS-related illnesses account for the majority of ICU admissions in more recent studies, in contrast to earlier eras of the AIDS epidemic. ⋯ In this article, we discuss the current state of knowledge regarding the impact of ART on incidence, etiology, and outcomes of critical illness among HIV-infected patients. In addition, we consider issues related to administration of ART in the ICU and identify important areas of future research.
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Review
HIV-associated lung infections and complications in the era of combination antiretroviral therapy.
The spectrum of lung diseases associated with HIV is broad, and many infectious and noninfectious complications of HIV infection have been recognized. The nature and prevalence of lung complications have not been fully characterized since the Pulmonary Complications of HIV Infection Study more than 15 years ago, before antiretroviral therapy (ART) increased life expectancy. ⋯ The Longitudinal Studies of HIV-Associated Lung Infections and Complications (Lung HIV) Study (ClinicalTrials.gov number NCT00933595) is a collaborative multi-R01 consortium of research projects established by the National Heart, Lung, and Blood Institute to examine a diverse range of infectious and noninfectious pulmonary diseases in HIV-infected persons. This article reviews our current state of knowledge of the impact of HIV on lung health and the development of pulmonary diseases, and highlights ongoing research within the Lung HIV Study.
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Among lung pathologies, α1AT, chronic obstructive pulmonary disease (COPD), emphysema, and asthma are diseases triggered by local environmental stress in the airway that we refer to herein collectively as airway stress diseases (ASDs). A deficiency of α-1-antitrypsin (α1AT) is an inherited genetic disorder that is a consequence of the misfolding of α1AT during protein synthesis in liver hepatocytes, reducing secretion to the plasma and delivery to the lung. Deficiency of α1AT in the lung triggers a similar pathological phenotype to other ASDs. ⋯ The PN is a network of chaperones and degradative components that generates and manages protein folding pathways responsible for normal human physiology. In ASD, we suggest that the PN system fails to respond to the increased burden of unfolded proteins due to genetic and environmental stresses, thus triggering pulmonary pathophysiology. We introduce the enabling concept of proteostasis regulators (PRs), small molecules that regulate signaling pathways that control the composition and activity of PN components, as a new and general approach for therapeutic management of ASDs.