FDA APPROVES TUDORZA PRESSAIR TO TREAT COPD
The US Food and Drug Administration (FDA) has approved Tudorza Pressair (aclidinium bromide) for the long-term maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.
Tudorza Pressair, a dry powder inhaler used twice daily, is a long-acting antimuscarinic agent that helps muscles around the large airways of the lungs stay relaxed to improve airflow.
The safety and efficacy of Tudorza Pressair were demonstrated in three randomized, placebo-controlled confirmatory clinical trials that included 1,276 patients ages 40 and older with a clinical diagnosis of COPD. Those treated had a smoking history of at least one pack a day for 10 years.
Tudorza Pressair may cause serious side effects, including paradoxical bronchospasm, new or worsened increased pressure in the eyes (acute narrow-angle glaucoma), or new or worsened urinary retention. Tudorza Pressair should not be used as a rescue therapy to treat sudden breathing problems (acute bronchospasm) and is not recommended for people younger than 18 years. The most common side effects reported by patients using Tudorza Pressair include headache, inflammation of the nasal passage (nasopharyngitis), and cough.
Tudorza Pressair is distributed by St Louis-based Forest Pharmaceuticals, a subsidiary of Forest Laboratories.
NEW TB DRUG REGIMEN PASSES ANOTHER SIGNIFICANT MILESTONE
Phase II clinical trial results show that the new tuberculosis (TB) combination drug regimen kills more than 99% of patients’ TB bacteria within 2 weeks and could be more effective than existing treatments. The results, published in the Lancet, add to a growing body of evidence that the new regimen could reduce treatment by more than a year for some patients.
The study, NC-001, or New Combination 1, was a 2-week trial successfully completed at two centers in South Africa. It involved the new combination therapy called PaMZ, consisting of the novel TB drug candidate, PA-824; moxifloxacin, an established antibiotic not yet approved for use in first-line TB therapy and being developed in partnership with Bayer Healthcare AG; and pyrazinamide, an existing TB drug. NC-001 was funded by the Bill & Melinda Gates Foundation, the United States Agency for International Development, UK Aid, and Irish Aid.
The results, along with preclinical data, suggest that this novel combination could treat both drug-susceptible and some forms of drug-resistant TB in only 4 months. Currently, people with multi-drug-resistant TB (MDR-TB) require 18 to 24 months of treatment. Even those with ordinary TB need 6 months of taking drugs every day.
“These findings confirm the promise of novel TB regimens to be shorter, simpler, safer, and, compared with today’s MDR-TB drugs, much less expensive,” said Mel Spigelman, MD, CEO and president of TB Alliance. “The next trial to advance this regimen is already under way. We now have real momentum toward bringing to market treatments that will ultimately help save millions of lives.”
A second trial called New Combination 2 (NC-002) was launched earlier this year to test the PaMZ combination over 2 months in patients, further advancing it through clinical development. Currently enrolling patients, NC-002 will be conducted at eight sites in South Africa, Tanzania, and Brazil, and will build global capacity for TB trials.
DRIVE-THROUGH FLU SHOT FEARS UNFOUNDED
Fainting following a flu shot is not justification for rejecting drive-through administration of the vaccine, according to researchers at the University of Louisville School of Medicine, in Kentucky, because syncope following influenza immunization is a rare event that can be managed.
“We found a person’s chance of fainting during a drive-through vaccination is less than the probability of being struck by lightning,” Ruth Carrico, associate professor in the infectious diseases division, said in a university news release.
Carrico’s team looked at data from a drive-through flu clinic hosted by the university that has administered more than 50,000 doses of flu vaccine since its inception in 1995. They found zero reports of fainting or related traffic crashes among those who received vaccinations by driving through the clinic.
This summer, Carrico plans to release a tool kit outlining how communities can organize and set up drive-through immunization clinics, including how to train staff and evaluate the clinics’ success. The researchers hope the tool kit “will increase the capacity and infrastructure of the nation to administer immunization or other emergency countermeasures quickly, efficiently, and safely,” Carrico said.
ADVERSE CHILDHOOD EXPERIENCES LINKED TO ADULT SMOKING PATTERNS IN WOMEN
New research finds that women who have been physically or emotionally abused were 1.4 times more likely to smoke. Having had a parent in prison during childhood doubled chances of women smoking.
Investigating the lasting impacts of adverse childhood experiences (ACEs), researchers across the United States collaborated to investigate the effects of psychological distress on the relationship between ACEs and current adult smoking. The ACE questionnaire was completed by more than 7,000 people, about half of whom were women.
After adjusting the data for factors known to affect a person’s propensity for smoking, such as their parents smoking during the subject’s childhood, the researchers found that these events can be tied up with adult smoking patterns, especially for women. Still, psychological distress increases the chances that any person, regardless of gender, will smoke, the authors note.
“Since ACEs increase the risk of psychological distress for both men and women, it seemed intuitive that an individual experiencing an ACE will be more likely to be a tobacco cigarette smoker,” said Tara W. Strine, PhD, who led the study. “However, in our study, ACEs increased the risk of smoking only among women. Given this, men who have experienced childhood trauma may have different coping mechanisms than their female counterparts.”
The authors also note that, when addressing smoking cessation in clinical practice, it may be important to understand not only psychological distress, but the underlying role of childhood trauma. They conclude: “Having knowledge about childhood trauma history in clinical practice may provide the opportunity to integrate trauma focused interventions.”
MECHANICAL VENTILATION EXACERBATES LUNG INFLAMMATION, SIMILAR TO INFECTIONS
Biophysical forces, including high transmural pressures generated by mechanical ventilation, trigger an innate immune response akin to what is launched when the body is fighting an infection, according to new research out of Ohio State University using human cell cultures.
The rhythmic pressure of ventilation stimulated the production of pro-inflammatory chemicals by activating proteins called toll-like receptors (TLRs) in lung cells, the research showed. TLRs recognize distinctive characteristics of pathogens and send out signals to activate other players in the immune system.
According to researchers, the results also suggest that microRNA is influential in the immune response because its behavior regulates the activation of the TLR proteins. As such, manipulating levels of either the microRNA or TLRs could be the basis for potential new treatment options for acute lung injury that requires ventilation.
“We showed that these cells respond to a mechanical force, pressure, as if it were an inflammatory stimulus. They almost perceive it as a bacterial toxin—and they don’t like it,” said Samir Ghadiali, associate professor of biomedical engineering at Ohio State and co-lead author of the study. “We didn’t know until this study how we could possibly turn off that type of mechanically induced inflammation. Essentially, we found two things that may help: microRNAs and two TLRs in the innate immunity pathway.”
VITAMIN D COULD PROVIDE PROTECTIVE BENEFIT TO LUNGS OF SMOKERS
Sufficient levels of vitamin D, defined as serum vitamin D levels of >20 µg/mL, provide a protective effect on lung function and the rate of lung function decline in smokers, according to research conducted at the Channing Laboratory, Brigham and Women’s Hospital.
Investigators concurrently assessed vitamin D levels and lung function at three different time points between 1984 and 2003.
In vitamin D deficient subjects, for each one unit increase in pack-years of smoking, mean FEV1 was 12 mL lower, compared with a mean reduction of 6.5 mL among subjects who were not vitamin D deficient. Over time, vitamin D deficiency exacerbated the effect of pack years of smoking on the decline in FEV1.
“Our results suggest that vitamin D might modify the damaging effects of smoking on lung function,” said lead author Nancy E. Lange, MD, MPH, of the laboratory. “These effects might be due to vitamin D’s anti-inflammatory and antioxidant properties.”
Assuming the results can be replicated in other studies, additional research should focus on whether vitamin D protects against lung damage from other sources, such as air pollution, according to the authors.
NEW LUNG GROWTH CAN OCCUR IN ADULT HUMANS
The adult human lung possesses a greater capacity for regeneration than previously thought, according to research published in the New England Journal of Medicine.
Following a 33-year-old woman after she underwent a right-sided pneumonectomy, investigators from Brigham and Women’s Hospital and Harvard Medical School observed increases in her vital capacity over the subsequent 15 years. Serial CT scans showed progressive enlargement of the remaining left lung and an increase in tissue density. Not only did the size of the lung increase, but there was a 64% increase in the number of alveoli. Researchers note that alveoli in the growing lung were shallower than in normal lungs.
Factors that may have contributed to the growth were the relatively young age of the patient at the time of surgery and stretching of the lung from post-pneumonectomy syndrome and exercise, the researchers suggested. After getting a prosthetic volume expander in the right lung cavity to ease dyspnea at 18 months, the patient exercised daily with a regimen of walking, cycling, and yoga.
“We hypothesize that, reminiscent of the role of stretch in lung development, cyclic stretch as such may be an important trigger for new lung growth,” the authors concluded. “Regardless of the specific mechanism, the findings in this patient support the concept that new lung growth can occur in adult humans.”
RESEARCH LINKS SUGAR, CANCER, VENTILATOR DEPENDENCE
A new avenue of molecular treatment for cancers, particularly lung cancer, may be on the horizon thanks to the discovery of new ways to use molecule microRNA-320a that could starve tumors and keep unused muscles strong.
In a new research report, Stanford scientists show that the molecule microRNA-320a is responsible for helping control glycolysis. Glycolysis is the process of converting sugar into energy, which fuels the growth of some cancers and contributes to the wasting of unused muscles such as the diaphragm when people are using ventilators.
“We [hope this discovery] can lead to a treatment to be given to intensive care unit patients who require the breathing machine, reducing the length of time they require the machine, and thereby reducing complications and deaths,” said Joseph B. Shrager, MD, a researcher involved in the work and professor of cardiothoracic surgery and chief of the division of thoracic surgery at Stanford University School of Medicine and VA Palo Alto Healthcare System in California.