Publications

This document presents the proceedings from the American Thoracic Society Climate Change and Respiratory Health Workshop that was held on May 15, 2010, in New Orleans, Louisiana. The purpose of the one-day meeting was to address the threat to global respiratory health posed by climate change. Domestic and international experts as well as representatives of international respiratory societies and key U.S. federal agencies convened to identify necessary research questions concerning climate change and respiratory health and appropriate mechanisms and infrastructure needs for answering these questions. After much discussion, a breakout group compiled 27 recommendations for physicians, researchers, and policy makers. These recommendations are listed under main issues that the workshop participants deemed of key importance to respiratory health. Issues include the following: (1) the health impacts of climate change, with specific focus on the effect of heat waves, air pollution, and natural cycles; (2) mitigation and adaptation measures to be taken, with special emphasis on recommendations for the clinical and research community; (3) recognition of challenges specific to low-resource countries when coping with respiratory health and climate change; and (4) priority research infrastructure needs, with special discussion of international needs for cooperating with present and future environmental monitoring and alert systems.

OBJECTIVE

To determine the validity of standardized screening assessments of cognitive functioning to detect neuropsychological impairment evaluated using a comprehensive battery in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

METHODS

This is a cross-sectional study using a combined cohort of 139 persons with SLE and 82 persons with RA. Screening cut points were empirically derived using receiver operating characteristic curves and threshold selection methods. Screening measures included the Hopkins Verbal Learning Test-Revised (HVLT-R) learning and delayed recall indices and phonemic fluency, a composite measure of the 3 cognitive screening tests, and the Perceived Deficits Questionnaire-Short Form (PDQ-SF), a self-report measure of cognitive symptoms. A comprehensive neuropsychological battery was administered as the "gold standard" index of neuropsychological impairment.

RESULTS

Rates of neuropsychological impairment were 27% and 15% for the SLE and RA cohorts, respectively. Optimal threshold estimations were derived for 5 screening techniques. The HVLT-R learning and phonemic fluency indices yielded the greatest sensitivity at 81%. The PDQ-SF yielded the lowest sensitivity at 52%. All measures were significantly associated with neuropsychological impairment after controlling for relevant sociodemographic covariates and depression.

CONCLUSION

These results suggest that telephone-administered screening techniques may be useful measures to identify persons with neuropsychological impairment. Specifically, measures of phonemic fluency and verbal learning appeared to be most sensitive and least likely to misclassify impaired individuals as cognitively intact. Self-reported questionnaires may have relatively decreased sensitivity compared to standardized interviewer-administered cognitive measures.

OBJECTIVE

To examine associations between CSF biomarkers, initial neurologic dysfunction, and long-term ambulatory outcome in dogs with acute intervertebral disk herniation (IVDH).

DESIGN

Prospective clinical study.

ANIMALS

54 dogs with acute thoracolumbar IVDH and 16 clinically normal dogs.

PROCEDURES

For each dog, variables, including CSF myelin basic protein (MBP), lactate, calcium, glucose, and total protein concentrations; nucleated cell count; and creatine kinase (CK) and aspartate aminotransferase activities, were measured. For dogs with thoracolumbar IVDH, initial neurologic function was characterized by use of a modified Frankel score (MFS; determined on a scale of 0 to 5, where 0 represented paraplegia with no deep nociception and 5 represented paraspinal hyperesthesia only). Long-term follow-up was assessed.

RESULTS

Among dogs with thoracolumbar IVDH, those with CSF CK activity ≤ 38 U/L had a 35-fold increase in the odds of long-term ambulation, compared with the odds in dogs with CSF CK activity > 38 U/L, adjusting for neurologic functioning at the evaluation. The CSF lactate, calcium, and glucose concentrations and aspartate aminotransferase activity were not predictive of long-term ambulatory outcome. Data analysis revealed that long-term functional recovery was > 98% for affected dogs, regardless of their initial MFS, when CSF CK activity was ≤ 38 U/L and MBP concentration was ≤ 3 ng/mL.

CONCLUSIONS AND CLINICAL RELEVANCE

In dogs with acute thoracolumbar IVDH, CSF CK activity and MBP concentration appeared to be prognostic indicators and, along with initial MFS, can be used to predict long-term ambulatory outcome.

BACKGROUND

The goals of asthma treatment include preventing recurrent exacerbations. Yet there is no consensus about the terminology for describing or defining "exacerbation" or about how to characterize an episode's severity.

OBJECTIVE

National Institutes of Health institutes and other federal agencies convened an expert group to propose how asthma exacerbation should be assessed as a standardized asthma outcome in future asthma clinical research studies.

METHODS

We used comprehensive literature reviews and expert opinion to compile a list of asthma exacerbation outcomes and classified them as either core (required in future studies), supplemental (used according to study aims and standardized), or emerging (requiring validation and standardization). This work was discussed at a National Institutes of Health-organized workshop in March 2010 and finalized in September 2011.

RESULTS

No dominant definition of "exacerbation" was found. The most widely used definitions included 3 components, all related to treatment, rather than symptoms: (1) systemic use of corticosteroids, (2) asthma-specific emergency department visits or hospitalizations, and (3) use of short-acting β-agonists as quick-relief (sometimes referred to as "rescue" or "reliever") medications.

CONCLUSIONS

The working group participants propose that the definition of "asthma exacerbation" be "a worsening of asthma requiring the use of systemic corticosteroids to prevent a serious outcome." As core outcomes, they propose inclusion and separate reporting of several essential variables of an exacerbation. Furthermore, they propose the development of a standardized, component-based definition of "exacerbation" with clear thresholds of severity for each component.

We retrospectively analyzed hematologic parameters in 22 patients with advanced, nonsquamous, NSCLC undergoing VEGF inhibition on a phase II clinical trial of bevacizumab, carboplatin, and gemcitabine. We also examined TTP in relation to hemoglobin changes. Median hemoglobin increased significantly from a 12.9 g/dL pretreatment to 13.8 g/dL (p =.01) after the second cycle of maintenance bevacizumab until the first off cycle measurement. There was no difference in TTP in patients who achieved a rise in hemoglobin compared with patients who did not (median 238 days vs. 268 days, p =.38.) Maintenance bevacizumab is associated with increased hemoglobin in advanced, nonsquamous, NSCLC patients.

Atrophy of the rotator cuff muscles is a factor that complicates the treatment of a massive rotator cuff tear (RCT). However, the molecular mechanisms that govern the development of muscle atrophy after RCTs have not been well defined. The Akt/mammalian target of rapamycin (mTOR) signaling pathway plays a central role in maintaining muscle mass in response to mechanical loading. The role of this pathway in the development of muscle atrophy after a massive RCT remains unknown. The purpose of this study was to investigate the regulation of the Akt/mTOR pathway in the development of muscle atrophy after a RCT and suprascapular nerve (SSN) injury. We evaluated the activity of the Akt/mTOR signaling pathway and how this pathway interacts with two atrophy-related genes, MuRF-1 and MAFbx, in supraspinatus muscles of rats that underwent unilateral complete rotator cuff tendon transection or SSN transection. Akt/mTOR activity was significantly reduced after tendon rupture, but increased after nerve injury. MuRF-1 and MAFbx were only up-regulated following denervation. These results suggest that tendon transection leads to a decrease in protein synthesis with down-regulation of the Akt/mTOR signaling pathway, whereas denervation leads to an increase in protein degradation via up-regulation of expression of MuRF-1 and MAFbx.