Ethambutol, a vital component of multidrug regimens for Mycobacterium avium complex (MAC) lung disease, can cause ocular toxicity if taken on a daily basis, according to a study in the second issue for July 2005 of the American Thoracic Society's peer-reviewed journal. Writing in the American Journal of Respiratory and Critical Care Medicine, the researchers recommended monthly visual acuity and color discrimination testing for patients taking doses of the drug greater than 15 to 20 milligrams per kilogram of body weight, those who receive the medication for longer than 2 months, and patients with renal insufficiency since the compound is cleared by the kidneys.
According to the investigators, the central fibers of the optic nerve are most commonly affected. The drug can cause blurred vision, decreased visual acuity, central blind or dark spots in the visual field, and often loss of the ability to detect green and sometimes red.
They point out, however, that ethambutol is a critical component of routine therapy for MAC disease which accounts for most mycobacterial infections other than tuberculosis in humans. MAC disease bacteria usually affect the lung, but may involve the lymph nodes, bones, joints, and skin. These bacteria are highly resistant to most antibiotics, but the infections they cause are not contagious. MAC infection in the lung usually develops slowly; the first symptoms generally involve coughing and spitting up mucus.
In this study, 229 patients with MAC lung disease received 16 months of multidrug therapy that included ethambutol. Patients on daily therapy received ethambutol at 25-mg/kg doses for the first 2 months, and then 15 mg/kg doses for the remainder of therapy. Patients on three-day-a-week therapy (Monday, Wednesday, and Friday) received a 25 mg/kg dose each day.
Of the 229 patients, 50 were known to have preexisting ocular disease.
The authors said that while on ethambutol, 97 patients consulted an ophthalmologist and 24, or 10 percent, stopped taking the drug temporarily. Eight of the 139 patients on daily therapy were diagnosed with ocular toxicity caused by the drug.
After they discontinued the drug, all patients with ocular disease caused by ethambutol returned to the same visual status they had prior to the start of the study.
KEY TO POTENTIAL VACCINE FOR COPD BACTERIA
Researchers believe that the acquisition and reasonably quick clearance of a bacterial strain called Moraxella catarrhalis from the lungs of chronic obstructive pulmonary disease (COPD) patients results in long-lasting, strain-specific protection from reacquisition and has important implications for vaccine development. The investigators assessed 104 adults with COPD for 81 months. They said that bacteria cause many of the exacerbations which characterize the disease and that such organisms, through chronic colonization, contribute to the airway inflammation that is the hallmark of the disease.
COPD is a term for lung diseases characterized by airflow obstruction that interferes with normal breathing. The two most frequent disease conditions that underlie COPD are severe emphysema and chronic bronchitis. Years of smoking are the primary cause for the diseases that underlie COPD, which, in 2002, claimed the lives of 120,000 Americans and cost the nation $37.2 billion.
In the study, the authors pointed out that 10.2 percent of the 560 exacerbations were likely caused by M. catarrhalis bacteria.
According to the authors, for the 20 million adults in the U.S. who have COPD, exacerbations occur at a rate of 1 to 2 annually. Based on their estimates, M. catarrhalis bacteria causes 2 to 4 million exacerbations annually in the U.S. Most individuals carried the organism M. catarrhalis for only a single monthly clinic visit. This relatively short duration of infection is in striking contrast to that observed for H. influenzae bacteria which colonized subsets of patients for a much longer time.
According to the researchers, the long-lasting, strain-specific protection offered by the acquisition and clearance of M. catarrhalis supports the concept that humans make protective responses that are capable of clearing the bacteria from the respiratory tract and preventing reacquisition. They said that their future work will focus on developing similar protective responses.
The study appears in the second issue for July 2005 of the American Thoracic Society's peer-reviewed American Journal of Respiratory and Critical Care Medicine.
VITAMIN D REPLETION REGIMEN FOR CF PATIENTS DID NOT WORK
The recently published vitamin D repletion regimen suggested by the Cystic Fibrosis Foundation's Consensus Panel on Bone Health for replacing the vitamin in cystic fibrosis (CF) patients has been called by researchers who tested it "strikingly ineffective." Out of 66 adults with CF, only 5 patients who had been treated with 50,000 international units of the vitamin per week for eight weeks had their serum levels corrected to the recommended degree.
The study was designed to determine the percentage of adults with CF who required the recommended vitamin D. repletion therapy because of serum levels below 30 nanograms per milliliter (30 ng/ml); to evaluate for the first time the effectiveness of a stepped up repletion protocol for CF patients; and to provide CF-specific data to assist in future optimal dosing.
Cystic fibrosis is a life-shortening inherited disorder that affects 30,000 persons in the U.S. Patients who are born with this problem produce abnormally thick and sticky mucus that often obstructs the lungs, leading to lung infections, as well as to the clogging of the pancreatic ducts which can prevent normal digestion. However, treatment for the disorder has improved greatly and predicted survival rates have increased from an average age of 25 in 1985 to over age 33 in 2005.
Since there has been an increase in survival, researchers have also been considering other health issues unique to the adult CF population. One issue is bone health because studies of bone density have determined that despite a young age, approximately 20 to 25 percent of adults with CF have osteoporosis and another 40 percent have osteopenia.
(Osteopenia is low bone volume due to inadequate replacement of bone loss from normal disintegration. Osteoporosis is abnormal loss of bone tissue, causing fragile bones that fracture easily.)
A adequate supply of vitamin D is needed for the body to absorb calcium from food and incorporate it into bone. A deficiency of vitamin D leads to abnormal bone growth and repair.
Of the 134 adults with CF in this study, 109 (81.3 percent) were found to have vitamin D levels below the recommended 30 ng/ml.
Of the 49 patients who started the second eight-week repletion test comprising a total of 800,000 international units of vitamin D, 33 completed the full course, but none corrected their vitamin D deficiency.
The authors noted that further research is required to determine the optimal level of vitamin D needed in order for CF patients to maximize calcium absorption and maintain bone health.
The research article appears in the second issue for July 2005 of the American Thoracic Society's peer-reviewed American Journal of Respiratory and Critical Care Medicine.
For the complete text of these articles, please see the American Thoracic Society Online Web Site at http://www.atsjournals.org. For either contact information or to request a complimentary journalist subscription to ATS journals online, or if you would like to add your name to the Society's twice monthly journal news e-mail list, contact Cathy Carlomagno at 212-315-6442, or at ccarlomagno@thoracic.org.
Journal
American Journal of Respiratory and Critical Care Medicine