Adam Gaffney

Protein Phosphatase 2A Regulates Innate Immune and Proteolytic Responses to Cigarette Smoke Exposure in the Lung

Protein phosphatase 2A (PP2A) is the primary serine-threonine phosphatase of eukaryotic cells, and changes in its activity have been linked to neoplastic and neurodegenerative diseases. However, the role of PP2A in noncancerous lung diseases such as chronic obstructive pulmonary disease (COPD) has not been previously examined. This study determined that PP2A activity was significantly increased in the lungs of advanced emphysema subjects compared with age-matched controls. Furthermore, we found that cigarette smoke exposure increases PP2A activity in mouse lung in vivo and in primary human small airway epithelial (SAE) cells in vitro. In mice, intratracheal transfection of PP2A protein prior to cigarette smoke exposure prevented acute smoke-induced lung inflammation. Conversely, inhibiting PP2A activity during smoke exposure exacerbated inflammatory responses in the lung. To further determine how PP2A modulates the responses to cigarette smoke in the lung, enzyme levels were manipulated in SAE cells using protein transfection and short hairpin RNA (shRNA) techniques. Increasing PP2A activity in SAE cells via PP2A protein transfection downregulated cytokine expression and prevented the induction of proteases following cigarette smoke extract (CSE) treatment. Conversely, decreasing enzymatic activity by stably transfecting SAE cells with shRNA for the A subunit of PP2A exacerbated these smoke-mediated responses. This study establishes that PP2A induction by cigarette smoke modulates immune and proteolytic responses to cigarette smoke exposure. Together, these findings suggest that manipulation of PP2A activity may be a plausible means to treat COPD and other inflammatory diseases.

The Affordable Care Act: implications for health-care equity

Inequalities in medical care are endemic in the USA. The Affordable Care Act (ACA), passed in 2010 and fully implemented in 2014, was intended to expand coverage and bring about a new era of health-care access. In this review, we evaluate the legislations impact on health-care equity. We consider the laws coverage expansion, insurance market reforms, cost and affordability provisions, and delivery-system reforms. Although the ACA improved coverage and access-particularly for poorer Americans, women, and minorities-its overall impact was modest in comparison with the gaps present before the laws implementation. Today, 29 million people in the USA remain uninsured, and substantial inequalities in access along economic, gender, and racial lines persist. Although most Americans agree that further reform is needed, the proper direction for reform-especially following the 2016 presidential election-is highly contentious. We discuss proposals for change from opposite sides of the political spectrum, together with their potential impact on health equity.

Moving Forward From the Affordable Care Act to a Single-Payer System

The authors discuss developments in the effort to achieve universal health care in the U.S. in 2016, particularly the implementation of the Affordable Care Act (ACA). Also cited are the ruling by the Supreme Court upholding the legality of the ACA subsidies, the claim by the Congressional Budget Office that will still be 27 million Americans who will be uninsured under the ACA, and some recommendations to resolve the shortcomings of the ACA in terms of coverage and costs.

The Neoliberal Turn in American Health Care

Leaving millions both uninsured and underinsured, the Affordable Care Act does not create a system of universal health care in the United States. To understand its shortcomings, we have to understand it as part of a historic shift in the political economy of American health care. This “neoliberal turn” began as a reaction against the welfare state as it expanded during the New Deal and post-World War II period. What began as a movement associated with philosophers like Friedrich Hayek ultimately had a powerful impact via the attraction of powerful corporate sponsors and political supporters, and it was to historically transform American health care thought and organization. In health policy circles, for example, it can be seen in a rising emphasis on “moral hazard,” overuse, and cost sharing above a concern with universalism and equity. It was likewise manifested by the corporatization of the health maintenance organization and the rise of the “consumer-driven” health care movement. By the time of the health care reform debate, the influence of corporate “stakeholders” was to prove predominant. These developments, however, must be construed as connected parts of a much larger political transformation, reflected in rising inequality and privatization, occurring both domestically and internationally.

Healing an ailing pharmaceutical system: prescription for reform for United States and Canada

Our pharmaceutical systems are broken, and only fundamental reform can ensure universal access to safer, more innovative, and more affordable drugs

Commuting mode and pulmonary function in Shanghai, China

Exposure to air pollution can be particularly high during commuting and may depend on the mode of transportation. We investigated the impact of commuting mode on pulmonary function in Shanghai, China. The Shanghai Putuo Study is a cross-sectional, population-based study. Our primary outcomes were forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) % predicted, and the secondary outcome was spirometric airflow obstruction. We tested the association between mode of transportation and these outcomes after adjusting for confounders. The study population consisted of 20 102 subjects. After adjusting for confounders, the change (95% CI) in FEV1 was −2.15% pred (−2.88– −1.42% pred) among pedestrians, −1.32% pred (−2.05– −0.59% pred) among those taking buses without air conditioning, −1.33% pred (−2.05– −0.61% pred) among those taking buses with air conditioning and −2.83% pred (−5.56– −0.10% pred) among those using underground railways, as compared to cyclists (the reference group). The effects of mode on FVC % predicted were in the same direction. Private car use had a significant protective effect on FVC % predicted and the risk of airflow obstruction (defined by Global Initiative for Chronic Obstructive Lung Disease but not by lower limit of normal criteria). Mode of transportation is associated with differences in lung function, which may reflect pollution levels in different transportation microenvironments. In Shanghai, China, certain modes of commuting to work are associated with reductions in pulmonary function http://ow.ly/TlyKT

A Case of Hypercalcemia Secondary to Hot Tub Lung

Hypersensitivity pneumonitis (HP) is a diffuse granulomatous lung disease resulting from inhalation of an antigen to which an individual has been previously sensitized. Hot tub lung is an increasingly common form of HP associated with inhalation of water aerosols containing Mycobacterium avium complex organisms that contaminate hot tub water. Granulomatous lung disorders, most classically sarcoidosis, have been associated with unregulated 1-α-hydroxylase expression by macrophages present in the granulomas, causing conversion of 25-OH-vitamin D to the active form of vitamin D, 1,25(OH)2 vitamin D, and, thus, hypercalcemia. To our knowledge, this is the first confirmed case of hypercalcemia secondary to elevated 1,25(OH)2 vitamin D levels associated with HP.

Disparities in pulmonary fibrosis care in the United States: an analysis from the Nationwide Inpatient Sample

BackgroundIdiopathic pulmonary fibrosis is a disease with high morbidity and mortality. Care for these patients, including lung transplantation, may provide significant benefits, but is resource-intensive and expensive. Disadvantaged patients with IPF may hence be at risk for receiving inferior care.MethodsWe analyzed data from the Nationwide Inpatient Sample, a database consisting of all hospitalizations from a 20% sample of US hospitals. We identified adults hospitalized with IPF between 1998 and 2011 using ICD-9 codes. We assessed the effect of insurance coverage and socioeconomic status (SES) on lung transplantation, a treatment that may improve survival. We also examined the effect of coverage and SES on mortality, as well as discharge to inpatient rehabilitation and receipt of a lung biopsy, two markers of the intensity of care delivered. We used multiple logistic regression to adjust for patient and hospital characteristics.ResultsWe identified 148,877 hospitalizations that met our definition of pulmonary fibrosis. In the main adjusted analyses, hospitalizations of patients with Medicaid (OR 0.30, 95% CI 0.16–0.57) or no insurance (OR 0.22, 95% CI 0.07–0.72) were less likely to result in a lung transplantation compared to hospitalizations of those with non-Medicaid insurance. Those of lower SES were also less likely to undergo transplantation, while hospitalized patients with Medicaid and the uninsured were less likely to be discharged to inpatient rehabilitation or to receive a lung biopsy.ConclusionsAmong hospitalized patients with IPF, those with lower SES, Medicaid coverage and without insurance were less likely to receive several clinical interventions.

Should US doctors mourn for Obamacare

Any changes to the Affordable Care Act are likely to result in fewer people being insured, worry Adam Gaffney and Zackary D Berger, but Saurabh Jha thinks reform could prioritise market forces and really make care affordable

Rebuttal From Drs Gaffney, Verhoef, and Hall.

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