BIRMINGHAM, ENGLAND--Just by examining the sputum, it is possible to tell which outpatients with acute exacerbations of chronic obstructive pulmonary disease (COPD) have a respiratory infection likely to require antibiotics. If the sputum is green or yellow, such an infection is probably present. But white or clear sputum suggests that a patient does not have a bacterial respiratory infection.

That was the conclusion of English researchers led by Robert A. Stockley, MD, who recently studied the relationship between sputum color and respiratory infection in 121 outpatients with acute COPD exacerbations.[1] The presence of green or yellow sputum was 94.4% sensitive and 77.0% specific for microbiologic evidence of respiratory infection, the researchers found.

Furthermore, most of the patients with yellow or green sputum had complete symptom resolution and an improvement in their sputum color after antibiotic treatment. "On the other hand, nearly all of the patients with white sputum improved without antibiotics," said Dr. Stockley in an interview with PULMONARY REVIEWS.

Physicians can use this information to better manage COPD exacerbations, which are often treated with antibiotics regardless of whether infection has been proved. "That's unintelligent medicine," stressed Dr. Stockley, a Professor of Medicine at the University of Birmingham in England.

The practice is common, however, because of the difficulty in distinguishing patients with acute COPD who would benefit from antibiotic therapy. "Bacteria are present in the sputum of 30% to 40% of COPD patients who are well versus about 50% to 60% of those with exacerbations, so the two groups really aren't much different," Dr. Stockley explained. Also, the efficacy of antibiotic therapy in acute COPD is unclear, and medical guidelines vary in their recommendations as to when such therapy should be initiated.[2,3,4]

SUBJECTS WERE IN PRIMARY CARE

The study subjects were recruited from primary care practices; they had presented with acute COPD exacerbations marked by dyspnea, cough, increased sputum production, elevated temperature, or malaise. All patients had a history of chronic bronchitis with daily sputum production for at least three months over two consecutive years.

Sputum samples were collected from each patient and matched against a standard color chart. Values of 1 and 2 on the chart corresponded with a white, milky, or opaque (mucoid) appearance. Values of 3 to 8 corresponded with progressively darker green-yellow (mucopurulent) colors, with the highest values reflecting the darkest sputum seen in cystic fibrosis patients. Sputum samples were always correctly identified as mucoid or mucopurulent, according to the study authors. Use of such a chart is possible, said Dr. Stockley, because the myeloperoxidase in neutrophils is green. The more neutrophils that are recruited into the lung during infection, the greener the sputum becomes.

After classification by color, sputum samples underwent microscopy and quantitative culture for the presence of bacteria and neutrophils. Blood samples were obtained from each patient as well, to permit measurement of C-reactive protein. Patients with mucopurulent sputum received antibiotic therapy, while those with mucoid sputum did not. More blood and sputum specimens were obtained two months after the start of the COPD exacerbation, once the patients were clinically stable.

MAJOR IMPROVEMENT IN BOTH GROUPS

At presentation, only 38% of the mucoid group had a positive sputum culture for bacterial pathogens. In contrast, 84% of the mucopurulent group had a positive sputum culture, and the number of bacteria was higher in this group as well. These differences were highly significant. In both groups, Haemophilus influenzae or H parainfluenzae were the organisms most often found.

Symptoms resolved without antibiotics in 32 of the 34 patients in the mucoid group. In none of these patients did the sputum color darken appreciably. In the remaining two patients, the sputum went from mucoid to mucopurulent soon after initial evaluation, a change that in both cases was associated with a positive sputum culture for H influenzae. These two patients improved after 14 days of treatment with a broad-spectrum antibiotic.

At follow-up, the patients in the mucoid group had rates of sputum cultures positive for bacterial pathogens (41%) and sputum samples with more than 25 neutrophils per low-power field (76%) that were comparable to those found initially. Their median C-reactive protein level, however, had fallen from 4.9 to 2.7 mg/L.

In the mucopurulent group, antibiotic therapy led to symptom resolution in 77 of the 87 subjects. With treatment, these patients' sputum color improved significantly; median values on the color chart fell from 4.0 at presentation to 3.0 at follow-up (see Figure 1). Moreover, their rate of sputum cultures positive for bacterial pathogens decreased to 38%, the bacterial counts fell, and the proportion of sputum samples containing more than 25 neutrophils per low-power field dropped from 98.9% to 80%. Their C-reactive protein levels declined, too, from a median of 14.5 mg/L at presentation to 2.7 mg/L at follow-up. "In other words, with antibiotic treatment, they became much more like the patients with white sputum," Dr. Stockley said.

Because of these findings, he recommended antibiotics for patients with acute COPD exacerbations who have green or yellow sputum, but not for those with white sputum. Dr. Stockley also suggested using the standard sputum color chart to tailor antibiotic therapy for each patient.

"For example, patients can use the chart to monitor their sputum and then notify their physician if it changes color, suggesting infection," he explained. "They can also monitor the color during treatment and let the physician know if there's no improvement after three to five days so the decision can be made to extend treatment or switch antibiotics."

When improvement does occur, it is vital to instruct patients not to stop treatment until their sputum clears and the antibiotic course is completed, Dr. Stockley emphasized. This will help to avoid incomplete treatment that contributes to antibiotic resistance.

--Timothy Begany

References
1. Stockley RA, O'Brien C, Pye A, Hill SL. Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD. Chest. 2000;117:1638-1645.
2. British Thoracic Society. BTS guidelines for the management of chronic obstructive pulmonary disease. Thorax. 1995;52(suppl):S1-S28.
3. American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1995;152(suppl):S77-S121.
4. Siafakas NM, Vermiere P, Pride NB, et al. Optimal assessment and management of chronic obstructive pulmonary disease (COPD). Eur Respir J. 1995;8:1398-1420.

Return to table of contents