Shawn P. Nishi

Augmentation of Myocardial Production of 15-Epi-Lipoxin-A4 by Pioglitazone and Atorvastatin in the Rat

Background— Both statins and thiazolidinediones have antiinflammatory properties. However, the exact mechanisms underlying these effects are unknown. We investigated whether atorvastatin (ATV) and pioglitazone (PIO) increase the myocardial content of lipoxin-A4 and 15(R)-epi-lipoxin-A4 (15-epi-LXA4), both arachidonic acid products with strong antiinflammatory properties. Methods and Results— In experiment 1, rats received 3-day pretreatment with water; PIO 2, 5, or 10 mg · kg−1 · d−1; ATV 2, 5, or 10 mg · kg−1 · d−1; or PIO 10 mg · kg−1 · d−1+ATV 10 mg · kg−1 · d−1. In experiment 2, rats received water; PIO 10 mg · kg−1 · d−1+ATV 10 mg · kg−1 · d−1; PIO+ATV and valdecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor; PIO+ATV and zileuton, a selective 5-lipoxygenase inhibitor; or zileuton alone. There were 4 rats in each group. Hearts were harvested and analyzed for myocardial lipoxin-A4 and 15-epi-LXA4 levels and for COX-2 and 5-lipoxygenase protein expression. ATV and PIO at 5 and 10 mg · kg−1 · d−1 significantly increased myocardial 15-epi-LXA4 levels compared with the sham-treated group (0.51±0.02 ng/mg). Myocardial 15-epi-LXA4 were significantly higher in the PIO+ATV group (1.29±0.02 ng/mg; P<0.001 versus each other group). Both valdecoxib and zileuton abrogated the PIO+ATV increase in 15-epi-LXA4, whereas zileuton alone had no effect. PIO, ATV, and their combination resulted in a small increase in myocardial lipoxin-A4 levels, which was not statistically significant. ATV alone or in combination with PIO markedly augmented COX-2 expression. PIO had a much smaller effect on COX-2 expression. Myocardial expression of 5-lipoxygenase was not altered by PIO, ATV, or their combination. Conclusions— Both PIO and ATV increase myocardial levels of 15-epi-LXA4, a mediator with antiinflammatory properties. This finding may explain the antiinflammatory properties of both PIO and ATV.

Emerging Bacterial, Fungal, and Viral Respiratory Infections in Transplantation

Kidney, liver, heart, pancreas, lung, and small intestine transplantations are viable therapeutic options for patients with end-stage organ failure. Ongoing advancements of surgical techniques, immunosuppressive regimens, and perioperative management have resulted in improved survival of allograft recipients. Despite these refinements, infections still contribute to substantial morbidity and mortality, limiting long-term success rates of these procedures. This article discusses the emerging bacterial, fungal, and viral respiratory infections in transplantation.

Oxygen Therapy Use in Older Adults with Chronic Obstructive Pulmonary Disease

Rationale Oxygen therapy improves survival and function in severely hypoxemic chronic obstructive pulmonary disease (COPD) patients based on two landmark studies conducted over 40 years ago. We hypothesize that oxygen users in the current era may be very different. We examined trends and subject characteristics associated with oxygen therapy use from 2001–2010 in the United States. Methods We examined Medicare beneficiaries with COPD who received oxygen from 2001 to 2010. COPD subjects were identified by: 1) ≥2 outpatient visits >30 days apart within one year with an encounter diagnosis of COPD; or 2) an acute care hospitalization with COPD as the primary or secondary discharge diagnosis. Oxygen therapy and sustained oxygen therapy were defined as ≥1 and ≥11 claims for oxygen, respectively, in the durable medical equipment file in a calendar year. Primary outcome measures were factors associated with oxygen therapy and sustained oxygen therapy over the study period. Results Oxygen therapy increased from 33.7% in 2001 to 40.5% in 2010 (p-value of trend <0.001). Sustained oxygen therapy use increased from 19.5% in 2001, peaked in 2008 to 26.9% and declined to 18.5% in 2010. The majority of subjects receiving oxygen therapy and sustained oxygen therapy were female. Besides gender, factors associated with any oxygen use or sustained oxygen therapy were non-Hispanic white race, low socioeconomic status and ≥2 comorbidities. Conclusions Any oxygen use among fee-for service Medicare beneficiaries with COPD is high. Current users of oxygen are older females with multiple comorbidities. Decline in sustained oxygen therapy use after 2008 may be related to reimbursement policy change.

Spirometry Use among Older Adults with Chronic Obstructive Pulmonary Disease: 1999–2008

RATIONALE Clinical practice guidelines recommend spirometry to diagnose chronic obstructive pulmonary disease (COPD) and facilitate management. National trends in spirometry use in older adults with newly diagnosed COPD are not known. OBJECTIVES To examine the rate and beneficiary characteristics associated with spirometry use in subjects with newly diagnosed COPD between 1999 and 2008. METHODS We examined newly diagnosed beneficiaries with COPD using a 5% Medicare population from 1999 to 2008. A new COPD diagnosis required two outpatient visits or one hospitalization with primary International Classification of Diseases, 9th edition code 491.xx, 492.xx, or 496 occurring at least 30 days apart with none in the prior 12 months. The primary measurement was spirometry performed within 365 days (±) of the first claim with a COPD diagnosis. MEASUREMENTS AND MAIN RESULTS Between 1999 and 2008, 64,985 subjects were newly diagnosed with COPD. Of these, 35,739 (55%) had spirometry performed within 1 year before or after the initial diagnosis of COPD. Spirometry use increased from 51.3% in 1999 to 58.3% in 2008 (P < 0.001). Subjects with younger age, men, whites, those with higher socioeconomic status, and those with a greater number of comorbidities were more likely to have spirometry. In a multivariable analysis, compared with 1999, subjects diagnosed in 2008 had 10% higher odds (odds ratio, 1.10; 95% confidence interval, 1.06-1.13) of having spirometry performed. CONCLUSIONS Despite an increase in the use of spirometry over time in newly diagnosed older adults with COPD, spirometry use remains low. Clinical practice guidelines and educational efforts should focus on increasing the use of spirometry to diagnose and manage COPD.

Concomitant pulmonary infection with Nocardia transvalensis and Aspergillus ustus in lung transplantation

Lung infections with Nocardia and Aspergillus spp in lung transplant recipients (LTRs) create diagnostic and therapeutic challenges. The present case illustrates the difficulties in identifying these pathogens in LTRs. A high degree of clinical suspicion and aggressive early management are required to ensure good outcomes. Although prospective data on treating these conditions are scarce, the empiric use of combination broad-spectrum anti-microbials initially seems prudent.

Mixing It Up: Coadministration of tPA/DNase in Complicated Parapneumonic Pleural Effusions and Empyema.

Background: A recent randomized controlled trial showed 12 serial doses of tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) is safe and effective in managing complicated parapneumonic pleural effusions and empyema (CPEE). However, this regimen is laborious, requiring trained personnel to open/close the chest tube 8 times daily for 3 days. We present our observational data using a simplified regimen of coadministered tPA/DNase. Materials and Methods: This is a retrospective observational study of patients who received coadministered tPA/DNase for CPEE from January 2012 to April 2015 at the University of Texas Medical Branch. Patient demographics, pleural fluid, radiologic and treatment characteristics, and outcomes were collected. Data are presented as proportions and percentages. Our primary outcome was successful treatment without need of surgery and discharge home alive. Secondary outcomes were dose and length of treatment and hospital stay, treatment complications, and 90-day mortality. Results: The study included 39 patients. All pleural effusions were loculated, 59% macroscopically purulent, 50% had a positive organism in Gram stain, and 40% were culture positive. A median of 6 (interquartile range, 3.5 to 6) doses were coadministered mainly via small bore chest tube (⩽14 Fr in 79%) with a median of 14.5 (interquartile range, 9.5 to 21.5) hospital days. Overall, 85% were successfully treated without need for surgery. Treatment failures occurred in 15%: 3/39 (7%) received surgery; 3/39 (7%) died. Only 1 (2.5%) complication of hemorrhagic pleural effusion resolved after discontinuation of intrapleural treatment. Conclusions: Our study shows intrapleural coadministration of tPA/DNase was effective and safe in management of CPEE.

Pulmonary Rehabilitation Utilization in Older Adults With Chronic Obstructive Pulmonary Disease, 2003 to 2012.

PURPOSE: To assess the trends in pulmonary rehabilitation (PR) utilization and factors associated with its use in older adults with chronic obstructive pulmonary disease (COPD). METHODS: We examined data for Medicare beneficiaries with COPD who received PR from January 1, 2003, to December 31, 2012. Persons with COPD were identified by (1) ≥2 outpatient visits >30 days apart within 1 year with an encounter diagnosis of COPD or (2) an acute care hospitalization with COPD as the primary diagnosis or a primary diagnosis of acute respiratory failure with a secondary discharge diagnosis of COPD. PR utilization was the study outcome identified by health care common procedure coding system codes G0237, G0238, G0239, and G0424 (after year 2010) or current procedural terminology codes (97001, 97003, 97110, 97116, 97124, 97139, 97150, 97530, 97535, and 97537) in a calendar year. RESULTS: Patients with COPD who received PR increased from 2.6% in 2003 to 3.7% in 2012 (P = .001). In a multivariable analysis, factors associated with receipt of PR were younger age, non-Hispanic white race, high socioeconomic status, multiple comorbidities (OR = 1.20; 95% CI = 1.13-1.27), and evaluation by a pulmonary physician (OR = 2.23; 95% CI = 2.13-2.33). Increased use of PR was attributed to prior users rather than new users of PR. CONCLUSIONS: Utilization of PR during the study period increased only 1.1% in these Medicare beneficiaries with COPD and remained low.

Pattern of Imaging after Lung Cancer Resection. 1992–2005

RATIONALE Imaging intensity after lung cancer resection performed with curative intent is unknown. OBJECTIVES To describe the pattern and trends in the use of computed tomography (CT) and positron emission tomography (PET) scans in patients after resection of early-stage lung cancer. METHODS Retrospective analysis of the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database. Subjects included 8,621 Medicare beneficiaries (age, ≥66 yr) who underwent lung cancer resection with curative intent between 1992 and 2005. A surveillance CT or PET examination was defined as CT or PET imaging performed in an outpatient setting on patients who did not undergo chest radiography in the preceding 30 days. MEASUREMENTS AND MAIN RESULTS Overall, imaging use was higher within the first 2 years versus Years 3-5 after surgical resection. Use of surveillance CT scans increased sharply from 13.7 to 57.3% of those diagnosed in 1996-1997 and 2004-2005, respectively. PET scan use increased threefold, from 6.2% in 2000-2001 to 19.6% in 2004-2005. In multivariable analyses, we observed a 32% increase in the odds of undergoing surveillance CT or PET imaging for every year of diagnosis between 1998 and 2005. There was no substantial decline in the odds of having a surveillance CT or PET scan during each successive follow-up period, suggesting no change in the intensity of surveillance over the first 5 years after surgical resection. The proportion of surveillance CT imaging performed at freestanding imaging centers increased from 18.0% in 1998-1999 to 30.6% in 2004-2005. CONCLUSIONS The use of CT and PET imaging for surveillance after curative-intent surgical resection of early-stage lung cancer increased sharply in the United States between 1997-1998 and 2005. In the absence of evidence demonstrating favorable outcomes, this practice was likely driven by prevailing expert opinion embedded in clinical practice guidelines made available during that time. Research is clearly needed to determine the role and optimal approach to surveillance thoracic imaging after surgical resection of lung cancer.

Timing and Outcomes of Tracheostomy Performed by Pulmonary and/or Critical Care Physicians

Background: Although pulmonary and/or critical care (P/CC) physicians perform percutaneous tracheostomy in mechanically ventilated patients, the trends, timing, and outcomes of this procedure have not been well described. This study aims to describe the trends, timing, and outcomes of this procedure. Methods: Using 5% medicare data, we retrospectively examined a cohort who had tracheostomy performed after initiation of mechanical ventilation during acute hospitalization to describe the timing of tracheostomy placement by pulmonary and/or critical care (P/CC) physicians and associated outcomes. Results: There were 4864 participants in the study cohort from 2007 to 2014. We examined the timing of tracheostomy (in days from initiation of mechanical ventilation), length of hospital stay, in-hospital death, and death within 30 days after hospital discharge. The percentage of tracheostomies performed by P/CC physicians increased significantly, from 7.2% in 2007 to 14.1% in 2014 (Cochran-Armitage test for trend, P = .001). Tracheostomies performed by P/CC physicians were more common in larger hospitals and major academic medical centers. After adjustment for baseline characteristics, the following parameters did not differ by provider: time to tracheostomy, length of hospital stay (days), in-hospital death, and death within 30 days after discharge. A tracheostomy was more likely to be performed by a P/CC physician at a larger (≥500 beds) hospital (adjusted odds ratio: 1.85, 95% confidence interval: 1.47-2.34). Conclusions: Tracheostomies are increasingly performed by P/CC physicians with similar outcomes, likely related to patient selection.

Pattern and Adherence to Maintenance Medication Use in Medicare Beneficiaries with Chronic Obstructive Pulmonary Disease: 2008-2013

Background: Maintenance medications provide symptomatic relief, improve lung function and reduce the risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Despite their proven benefits, limited information exists on maintenance medication use and adherence among users. Objective: We examined the patterns and factors associated with the receipt of and adherence to maintenance medication in individuals with COPD. Methods: A retrospective cross-sectional study of 5% of Medicare beneficiaries enrolled in Parts A, B and D with COPD who received maintenance medication from 2008 to 2013 was conducted. Maintenance medication includes: inhaled corticosteroids (ICSs), long-acting beta2- agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) alone or in combination. We examined the proportion of beneficiaries with COPD who had at least one prescription filled for maintenance medication. Among users of maintenance medications, we also examined adherence, defined as proportion of days covered (PDC) ≥80% over the year from the first maintenance medication prescription fill date. Results: Overall, maintenance medication (LAMAs, LABAs, ICSs and/or LABA/ICS) use increased from 67.8% in 2008 to 72.1% in 2013. The increase is related to increases in use of LABA/ICS, which rose from 41.1% in 2008 to 49.6% in 2013. Factors associated with receipt of maintenance medication include female gender, recent COPD hospitalization (odds ratio [OR] 1.63; 95% confidence interval [CI] 1.54-1.73), oxygen therapy (OR 1.74 95% CI, 1.68-1.81), dual eligibility status (OR 1.45; 95% CI 1.39-1.51), higher education level and evaluation by a pulmonary provider (OR 1.88; 95% CI 1.81-1.96). The overall adherence among maintenance medication users remained flat. The most important factor associated with adherence was dual eligibility status (OR, 1.67; 95% CI: 1.59-1.75). Conclusions: Receipt of maintenance medications increased during the study period and was higher in those with dual eligibility. Overall, adherence to maintenance medications was suboptimal and remained unchanged.