COPD and Respiratory Health Spotlight

Link Identified Between Brain Atrophy and Respiratory Infections in Elders

Brain atrophy, a marker of neurodegeneration, is frequently seen on computed tomography (CT) scans of elderly persons. Neurodegeneration is associated with functional impairment, including dysphagia, which can cause aspiration pneumonia and lower respiratory tract infections (LRTIs). According to a recent study by Reiko Okada, Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Japan, and colleagues, assessing the severity of brain atrophy in elderly patients may be useful in identifying increased risk of LRTIs. The study was published in Clinical Interventions in Aging.

The study included 51 nursing home residents aged 60 to 96 years, none of whom had hemiparesis, major neurological dysfunction, or symptoms of dysphagia at baseline. All participants underwent a non-contrast brain CT scan, approximately half of which showed severe atrophy in any lobe. The incidence of LRTIs over the course of 4 years was determined in the study population by identifying the following: body temperature ≥100.4°F (≥38.0°C), presence of two or more respiratory symptoms, and use of antibiotics. When the incidence of LRTIs was compared with the severity and type of brain atrophy, the researchers found that the incidence rate ratio for LRTIs was higher in residents with severe brain atrophy than in those without severe brain atrophy, a finding that maintained statistical significance even after adjusting for confounding factors (odds ratio, 4.60; 95% confidence interval, 1.18-17.93; fully adjusted P=.028). Furthermore, the researchers noted that the incidence of LRTIs was significantly higher in patients with frontal lobe atrophy (P=.024) or parietal lobe atrophy (P=.018).

Because LRTIs are a major cause of morbidity and mortality in elderly persons, the results of the study indicate the need for more effective methods of determining risk of respiratory infections in long-term care facilities. According to Okada and associates, a swallowing test using videofluoroscopy is not always easily accessible in the nursing home setting, and observation-based bedside evaluation of swallowing can be subjective and does not always reveal aspiration. They concluded, “The use of CT imaging is increasing worldwide, and there are several situations in which brain CT scans are routinely performed in elderly subjects (eg, evaluation of dementia and minor head injury). Although we do not advocate brain CT just to assess the risk of LRTI, we do suggest that brain CT scans taken for other purposes should be evaluated to determine the risk of subsequent LRTI, which has a high risk of mortality in nursing home residents.”

Respiratory Tract Infections Associated With Increased Fall Risk in Nursing Home Residents

Falls represent a multifactorial problem in the nursing home. Falls are frequently attributed to cognitive impairment, functional impairment, environmental hazards, medications, and frailty syndrome, among other causes. However, it is not as clear whether a fall can be directly attributed to an infectious disease, which are also highly common in the elderly nursing home population. In a new study published in the Polish Archives of Internal Medicine, Malgorzata Piglowska, PhD,
Department of Geriatrics, Medical University of Lodz, Poland, and colleagues assessed the relationship between respiratory tract infections (RTIs) and the incidence of falls. The study involved 255 residents aged 65 years and older from three nursing homes. Over 1 year, the researchers documented the number of falls (with and without fracture) and the number of episodes of infection (defined as common cold symptoms, flu symptoms, or pneumonia persisting for more than 2 days). Among 104 residents who experienced a fall, 77.9% had at least one infection during the year. Among 17 residents who experienced a fall-related fracture, 88.2% had at least one infection during the year. In the analysis, Piglowska and associates reported that even after adjusting for other covariates, RTI is an independent predictor of incidence of both falls and falls with a fracture. “Early identification of older people with RTI as being those with a high risk of falling will enable preventive action to be taken at the right time,” they wrote. Furthermore, they concluded that prevention of infection is likely to reduce the number of falls and fractures in nursing home patients overall.

Roflumilast Has Safe Cardiovascular Profile

Among patients with mild to moderate chronic obstructive pulmonary disease (COPD), the leading cause of morbidity and mortality is cardiovascular disease. Thus, evaluating the cardiovascular safety profile of new COPD medications is important, especially among older adults, who tend to have more comorbidities than younger patients. A recent study by William B. White, MD, Calhoun Cardiology Center, University of Connecticut School of Medicine, and associates sought to evaluate the cardiovascular safety of roflumilast compared with placebo. The results of their study were published in February in CHEST. In March 2011, roflumilast was approved by the FDA to decrease the frequency of flare-ups and prevent worsening of symptoms from severe COPD. White and colleagues pooled data from intermediate- and long-term placebo-controlled clinical trials of roflumilast in COPD. The studies comprised 12- to 52-week placebo-controlled trials that included more than 12,000 patients with moderate to very severe COPD (average age, 64 years). They assessed for major adverse cardiovascular events (MACE; ie, myocardial infarction, death, stroke). From more than 6500 patients taking roflumilast, 52 patients experienced a MACE (14.3 per 1000 patient-years), compared with 76 patients from the 5500 patients taking placebo (22.3 per 1000 patient-years); the MACE composite rate was significantly lower in the roflumilast group compared with the placebo group (hazard ratio vs placebo, 0.65; 95% confidence interval, 0.45-0.93; P=.019). “The implications of our study is that roflumilast was not found to have a cardiovascular safety concern,” said White in an interview with Annals of Long-Term Care: Clinical Care and Aging.^® “The original studies compiled for this analysis were the typical safety and efficacy studies and not designed to determine or define a cardioprotective effect of roflumilast; hence, this study should not be considered evidence for a protective effect of this drug.” However, as patients with COPD have increased rates of cardiovascular morbidity and mortality, particularly when severely ill, “new agents for the treatment of COPD should have some evidence that they do not increase harm when approved for use in the United States,” White said.

Aclidinium Bromide Demonstrates Improvement in Static Lung Function and Exercise
Endurance in Patients With COPD

Aclidinium bromide is an anticholinergic indicated for the long-term treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. The FDA approved the agent in 2012 following three randomized clinical trials that demonstrated the drug’s safety and efficacy to improve airflow in COPD patients. New clinical evidence supporting the use of aclidinium bromide was presented during the 2013 American Thoracic Society International Conference. Two posters presented different patient outcomes gleaned from a double-blind, randomized, crossover study involving 112 patients with moderate to severe COPD (mean age, 60.3 years).

Kai Beeh, MD, Insaf Respiratory Institute, Wiesbaden, Germany, and colleagues evaluated the effects of aclidinium bromide on dynamic hyperinflation, exercise endurance time, and dyspnea (doi: 10.1164/ajrccm-conference.2013.187.1_MeetingAbstracts.A2430). Patients were randomly assigned to receive aclidinium bromide 400 µg twice daily or placebo for 3 weeks. They performed constant-load exercise at a 75% peak incremental exercise work rate, with the primary end point being change in level of endurance from baseline to week 3. The results showed that at week 3, patients taking aclidinium bromide improved significantly in exercise endurance time (P=.021).

In the other study, Henrik Watz, MD, Pulmonary Research Institute, Hospital Grosshansdorf, Germany, and associates investigated the effects of aclidinium bromide therapy on improving static lung function and hyperinflation—two important therapeutic goals in COPD treatment (doi:10.1164/ajrccm-conference.2013.187.1_MeetingAbstracts.A2431). The patients received either aclidinium bromide 400 µg twice daily or placebo for 3 weeks. The researchers measured trough inspiratory capacity (IC) and forced expiratory volume in 1 second trough and 2-hour post-dose functional residual capacity, residual volume, total lung capacity, and specific airway conductance. The results showed that compared with placebo, aclidinium bromide significantly increased adjusted mean trough IC and forced expiratory volume from baseline to week 3 (P=.02). The authors further concluded that these improvements in static lung function at 2 hours post-dose were significantly greater for aclidinium bromide than for placebo (all P<.001).