Press Release

August 2004

High Dietary Fiber Can Reduce Cough with Phlegm

A diet high in fiber from fruit and soy foods can reduce the incidence of chronic respiratory symptoms, especially cough with phlegm production, according to data from the Singapore Chinese Health Study.

Writing in the first issue for August 2004 of the American Thoracic Society’s peer-reviewed American Journal of Respiratory and Critical Care Medicine, Lesley M. Butler, Ph.D., of the Department of Epidemiology and Preventive Medicine, University of California at Davis, Davis, California, along with four associates, studied the details from 571 cases of incident cough with phlegm, along with research information collected from 44,068 men and women who did not suffer from the respiratory problem.

“Our prospective data support the role of diet in the etiology of cough with phlegm production,” said Dr. Butler. “In particular, nonstarch polysaccharides, a major component of dietary fiber, and certain noncitrus fruits, including apples and grapes, were independently associated with reduced development of cough with phlegm.”

The researchers administered a 165-item quantitative food frequency questionnaire that was developed for and validated by the men and women in the study. With ages ranging from 45 to 74, they were all either permanent residents or citizens of Singapore and formed part of two major Chinese dialect groups. Their survey follow-up, completed in August 2003, assessed their usual diet over the past year. It contained 16 items on individual fruits and juices, 24 questions on 34 specific vegetables, and 7 queries on soy food items.

Members of the cohort who suffered from incident phlegm were more likely to be male, older, and members of one dialect group, compared with noncases. The cases, regardless of symptom duration, were more likely to be current smokers, to have started smoking before age 20, and to be heavier smokers.

The investigators noted that fruit, vegetable, and grain products were the major contributors of nonstarch polysaccharides in this population. (Polysacharides are carbohydrates composed of more than one monosacharide, but usually not more than four.)

“The incidence of cough with phlegm was reduced with high intake of fruit, but not vegetable or grain products,” said Dr. Butler. “It is possible that fiber from fruit may have physiologic effects that are more beneficial in reducing development of cough with phlegm than fiber from vegetables or grain products.”

The researchers believe that other components in fruit, in addition to fiber, such as individual flavonoids, could also have been important in protecting against chronic cough. Among the many properties of the aromatic compounds called flavonoids are those that account for the yellow, red, and blue pigmentation in fruit, plus its antioxidant and anti-inflammatory properties.

The investigators noted that they observed an association between high consumption of fruits high in flavonoids such as apples, grapes, and pears and lower levels of incident cough with phlegm.

They said that their data provides evidence that promoting a diet high in fiber and flavonoids, such as fruit and soy, might make an important contribution to primary prevention strategies for chronic respiratory symptoms, both in smokers and nonsmokers.

Can Brief Exposure to Multidrug Resistant Tuberculosis Cause Infection?

The use of a rapid new molecular technique, based on a blood sample, to detect antigen specific T cells related to multidrug-resistant tuberculosis (TB) infection has allowed investigators to identify probable low dose M. tuberculosis infection in individuals who have had limited contact with a diagnosed case.

Writing in the first issue for August 2004 of the American Thoracic Society’s peer-reviewed American Journal of Respiratory and Critical Care Medicine, Ajit Lalvani, M.D., of the Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, United Kingdom, studied 92 individuals who were exposed to a 24-year-old Moldovan female who was diagnosed with multidrug-resistant TB infection several weeks after she had given birth to a healthy baby at the maternity unit of University Hospital of Modena, Italy. Since the highly infectious case had been present in the unit for 4 days, all mothers, relatives and neonates (in their first week of life) who had been there at the same time faced a potentially serious health risk.

Of the 92 individuals identified from records as having been present in the maternal unit with the index case, 88 had only hospital-based contact and 4 had household and hospital contact.

While housed in the maternity unit, mothers were admitted either to one of three rooms with six beds each, or one of two rooms with three beds. The women slept in the same room overnight, shared the same table for meals, and used the same lavatory. The index case was admitted in late November when windows and doors were almost always shut and no air conditioning or ducted ventilation was in use. Mothers had their babies close to their beds during the day, while, at night all babies slept in the nursery without the mothers.

There were 51 adults and 41 newborns in the exposed group. Only 2 persons had had a prior history of TB exposure. Among the exposed group were 26 males and 66 females.

The contacts were given a tuberculin skin test (TST), and their blood was tested with the T cell-based assay. The molecular test, but not the TST, suggested quite extensive hospital-based transmission of multidrug-resistant M. tuberculosis after brief exposure.

Those individuals with TST and molecular test positive results underwent chest radiography and high resolution computed tomography. All contacts were deemed normal by radiologists except for the Italian-born husband of the index case. His high resolution computed tomography showed several small chest areas of concern.

“Our results help to explain the apparent importance of casual contact for TB transmission, and may have implications for prevention,” said Dr. Lalvani.

The authors said that their findings of TST negative readings, as compared with molecular test positive results raise the question of risk potential: whether those who had molecular test positive results would progress to active TB similar to individuals who have had a positive skin test.

The participants in the study were enrolled in a long-term surveillance program, according to the investigators.

H. influenzae Bacteria Present Even After Negative Cultures From Sputum of Chronic Obstructive Pulmonary Disease Patients

Haemophilus influenzae, an important bacterial cause of lower respiratory infections resulting in exacerbations of chronic obstructive pulmonary disease (COPD), is present far more often in the respiratory tract of adults with COPD than is apparent on the basis of sputum culture. The research results are published in the first issue for August 2004 of the American Thoracic Society’s peer-reviewed American Journal of Respiratory and Critical Care Medicine.

Timothy F. Murphy, M.D., of the Medical Research Section, Buffalo Veterans Affairs Medical Center, Buffalo, New York, along with three associates, studied isolates of H. influenzae collected monthly over a 7-year period from 104 patients between March 1994 and December 2000. Within this period, the investigators found 122 instances of a gap of 1 month or more of negative cultures followed by isolation of an apparently identical strain of H. influenzae. Seventeen such episodes lasting 6 months or more were studied in detail to test the hypothesis that these periods of negative cultures actually represented continuous colonization of the lungs by the same strain of H. influenzae in the COPD patients.

In COPD, patients have persistent obstruction of the airways associated with either emphysema or chronic bronchitis. Following years of cigarette smoking, emphysema can enlarge the tiny air sacs in the patient’s lungs and destroy the walls. Persistent cough that produces sputum is the hallmark of chronic bronchitis in COPD. In the U.S., the condition is the fourth leading cause of death and its incidence is increasing throughout the world.

“Molecular typing by three independent methods established that the strains preceding and following the episodes of negative cultures were indeed identical,” said Dr. Murphy. “Strain-specific H. influenzae DNA was detected in some of the sputum samples that yielded negative cultures. These results indicate that some patients with COPD are persistently colonized with H. influenzae and that sputum cultures underestimate the frequency of colonization of the respiratory tract by H. influenzae in COPD.”

The investigators believe that their observations could have a significant impact on the understanding of bacterial colonization in COPD.

“Because H. influenzae is known to induce airway inflammation, studies that have compared markers of airway inflammation in the presence and absence of bacteria on the basis of sputum results required careful reinterpretation,” said Dr. Murphy. “The observation that H. influenzae is present far more often than is revealed by sputum culture should be considered in the design of future studies to elucidate the role of chronic bacterial colonization in airway inflammation and in studies of the role of bacteria in the course and pathogenesis of COPD.”

Combination Antibiotic Therapy Lowers Death Rate Significantly in Critically Ill Patients with Pneumococcal Bacteremia

Combination antibiotic therapy improved survival significantly among critically ill patients who had severe pneumonia with complicating bacteremia, according to published results from an international prospective, observational study.

Writing for the International Pneumococcal Study Group in the second issue for August 2004 of the American Thoracic Society’s peer-reviewed American Journal of Respiratory and Critical Care Medicine, Victor L. Yu, M.D., of the Infectious Disease Section, Veterans Administration Medical Center, Pittsburgh, Pennsylvania, along with 13 associates, studied 844 consecutive patients with bacteremic pneumococcal pneumonia who were treated in 21 hospitals in 10 countries on 6 continents. They were enrolled in the study between December 1, 1998, and January 2001.

“Streptococcus pneumoniae remains the most common cause of death among patients with severe pneumonia and the prognosis is worse for those who develop complicating bacteremia,” said Dr. Yu.

(Bacteremia is the presence of bacteria in the blood. It is a relatively common occurrence and usually causes no symptoms since white blood cells rapidly remove the bacteria. However, sometimes there are too many bacteria to be removed easily and they overwhelm the white cells, resulting in a serious disease complication.)

Among the 844 adult patients with bacteremia due to Streptococcus pneumoniae in the study, there were 94 who were critically ill. The combination antibiotic therapy received by 47 resulted in a 14-day mortality rate of 23.4 percent as contrasted with 55.3 percent mortality rate for the 47 on monotherapy.

“This improvement in survival was independent of the country of origin, intensive care unit support, class of antibiotics, or in vitro activity of the antibiotics prescribed,” said Dr. Yu.

The authors said that, to their knowledge, this work represented the first prospective evaluation of the impact of combination therapy on mortality in severe pneumonia with complicating bacteremia.

Among the balance of the patients who were not critically ill, the 14-day mortality rate was not significantly different between either the combination or monotherapy treatment groups. Overall, of the 844 patients, 16.5 percent (139) died by Day 14 of their treatment.

The risk of death was almost eightfold greater for critically ill patients compared with patients who were less ill upon hospital admission.

The authors said that the optimal duration of combination therapy remained undefined; however, since mortality was highest within the first 3 days after admission, it seemed both “intuitive and reasonable” that 3 to 5 days of antibiotic treatment “might be sufficient.”

The point out that if their conclusions are confirmed by other prospective studies, using their approach could be beneficial to patients, while still minimizing antibiotic overuse.

Screening for Obstructive Sleep Apnea in Commercial Drivers

In an effort to develop a simpler test to identify commercial truck drivers who suffer from severe sleep apnea and who might fall asleep at the wheel, medical investigators have developed a two-stage strategy combining questions about three symptoms of sleep apnea, with body weight data, plus a test for oxygen concentration in the blood when needed, to produce a 91 percent predictive rate for the disorder, according to a study published in the peer-reviewed journal of the American Thoracic Society.

Writing in the second issue for August 2004 of the American Journal of Respiratory and Critical Care Medicine, Indria Gurubhagavatula, M.D., M.P.H., of the Center for Sleep and Respiratory Neurobiology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, used the two-stage approach with 406 commercial drivers to uncover cases of severe apnea. Utilizing a level of five or more sleep apnea episodes per hour to define any apnea, 114 drivers were shown to be affected with mild to moderate apnea; in addition, 19 drivers had 30 or more episodes per hour to demonstrate severe sleep apnea.

Sleep apnea is a serious sleep disorder in which an affected person pauses in their breathing during sleep for 10 seconds or more and then resumes breathing after a very brief arousal. This process, repeated over and over during the night, allows carbon dioxide to build up in the blood and brain, and oxygen levels to decrease. Obese men are at greatest risk for the disorder.

According to the authors, sleepiness has been shown to account for between 31 to 41 percent of major crashes of commercial vehicles. In 2001, large trucks were involved in 429,000 crashes. Nearly 5,000 of these crashes were fatal, which amounted to 12 percent of all U.S. traffic deaths. An additional 130,000 victims suffered nonfatal injuries. These accidents cost $76,637 per crash, but rose to $3.54 million after a fatal accident.

“Our results are particularly useful,” said Dr. Gurubhagavatula, “because confirmatory polysomnography testing is expensive and often inaccessible.”

The authors said that the simplest strategy they explored depended on responses to questions about three apnea-related symptoms. They also chose to look at body mass index (BMI) because obesity is a major obstructive sleep apnea factor. In addition, they developed a risk score that combined information about symptoms with BMI data, as well as age and sex, in a tool that the researchers called the multivariable apnea prediction index.

Among the study participants, over 93 percent were male, and had an average age of 44.4. The sample consisted of 85 percent white persons, 12.5 percent African-Americans, and 1.9 percent Hispanics. Approximately half of the group were obese, with another 38 percent overweight.

“Our study raises the question of whether commercial drivers should be screened routinely for severe obstructive sleep apnea, perhaps during preemployment physical examinations,” said Dr. Gurubhagavatula. “Our study is the first step toward addressing this question; the two-stage screening strategy we propose is optimal and highly accurate in excluding severe apnea.”

Opportunistic Pathogen Makes Airflow Restriction Worse in Chronic Obstructive Pulmonary Disease Patients

Researchers have demonstrated that there is a strong association between severity of airflow restriction in patients with chronic obstructive pulmonary disease, especially in those with severe illness, and colonization with an opportunistic pathogen called Pneumocystis, according to a study published in the second issue for August 2004 of the American Thoracic Society’s peer-reviewed American Journal of Respiratory and Critical Care Medicine.

Alison Morris, M.D., M.S., of the Division of Pulmonary and Critical Care Medicine, University of Southern California, Los Angeles, California, along with seven associates, conducted a cross-sectional analysis on tissue from 68 smokers with varying severity of COPD who underwent lung resection and lung transplantation. In addition, they examined tissue from 44 control subjects who received lung transplants for diagnoses other than COPD. They checked Pneumocystis colonization rates both in lung tissue obtained from the smoking subjects, and in the lung transplant control patients. Using nested polymerase chain reaction techniques, they detected colonization in almost 37 percent of the 30 smoking patients who had very severe COPD (11 patients). This figure contrasted sharply with the detection of Pneumocystis in 5.3 percent of the 38 smoking patients with either normal lung function or less severe COPD (2 patients). Among the 44 control subjects, 9.1 percent (4 patients) were colonized.

Pneumocystis is an opportunistic pathogen that causes pneumonia in immunocompromised individuals and, according to the authors, could be a pathogen involved in the progression of COPD

“Although nonimmunosuppressed hosts rarely develop Pneumocystis pneumonia or PCP, use of the polymerase chain reaction has demonstrated that some groups of subjects have low levels of Pneumocystis DNA present in their lungs,” said Dr. Morris. “Pneumocystis in these cases, which likely represent colonization or asymptomatic carriage, may lead to an exaggerated lung inflammatory response consisting primarily of CD8+ lymphocytes and neutrophils. These same cell types are thought to be important in the pathogenesis of COPD, and their numbers in the lung correlate with severity of airflow obstruction.”

In COPD, patients have persistent obstruction of the airways associated with either emphysema or chronic bronchitis. Following years of cigarette smoking, emphysema can enlarge the tiny air sacs in the patient’s lung and destroy the walls. Persistent cough that produces sputum is the hallmark of chronic bronchitis in COPD. In the U.S., the condition is the fourth leading cause of death, and its incidence is increasing throughout the world.

Most of the 68 smokers involved in the study were male (73 percent) and their median age was 60. The median pack years associated with their habit was 60, and their mean lung function test results were 46 percent of predicted values.

Among the 44 control subjects who underwent transplantation for diagnoses other than COPD, 15 patients had cystic fibrosis and 12 had idiopathetic pulmonary fibrosis. None of these persons had a history of either PCP or immunodeficiency syndrome. They were a younger group than the smokers at a median age of 42.

“We have thus shown an association between Pneumocystis colonization and severity of COPD and demonstrated that colonization is not a result of other clinical factors or comorbid conditions,” said Dr. Morris.