ease in the jail population, the cost may be as low as $5,700 or Los Angeles County
as high as $62,500 per case detected, according to Jones and Department of Health Services—Public Health
Schaffner. Tuberculosis can kill or cripple a person if undetec- Los Angeles, California
ted, untreated, or neglected. It is my opinion that the general
public supports spending whatever it takes to prevent the
spread of communicable diseases. Tuberculosis in particular is References
of major concern because it is an airborne pathogen and infec- 1. Centers for Disease Control. A strategic plan for the elimination of tuber-
tion can remain dormant for many years before becoming ac- culosis in the United States. MMWR 1989;38(Suppl S-3):1–25.
tive and infectious. It also has not been effectively controlled 2. Institute of Medicine. Division of Health Promotion and Disease Preven-
with a vaccine. However, as the disease is perceived as declin- tion. In: Geiter L, editor. Ending neglect: the elimination of tuberculo-
ing and receding more and more into limited segments of the sis in the United States. Washington DC: National Academy Press;
U.S. population such as jail and prison inmates, complacency 2000. Chapter 2, p. 23–50.
3. Jones T, Schaffner W. Miniature chest radiograph screening for tubercu-
becomes a real threat to the prospect of eliminating tuberculo- losis in jails: a cost-effectiveness analysis. Am J Respir Crit Care Med
sis. The public as well as public health officials will need to 2001;164:77–81.
persist in accepting the importance of tuberculosis as a public 4. National Center for Devices and Radiological Health. The selection of
health threat not only for those in jails, as suggested by Jones patients for x-ray examination: chest x-ray screening examinations.
and Schaffner, but for the local as well as world community Rockville, MD: Food and Drug Administration, 1983, Health and Hu-
until this dangerous and persistent disease is truly eliminated. man Services Publication (FDA), 83-8204.
5. Centers for Disease Control and Prevention. Recommendations for pre-
Certain time-tested technologies such as targeted chest radi- vention and control of tuberculosis among foreign-born persons: Re-
ography will likely continue as a valuable tool in this endeavor. port of the Working Group on Tuberculosis Among Foreign-Born per-
PAUL T. DAVIDSON, M.D. sons. MMWR 1998;47(RR-16):1–26.
Director of Tuberculosis Control
Bronchial Eosinophilia in Exacerbation of Bronchitis
An Allergic Profile of Inflammation?
Cigarette smoking is associated with airway inflammation. hybridization on bronchial biopsies and postulated that an “al-
Susceptible smokers may develop complex disease manifesta- lergic profile” of inflammation including the CD4 T-helper
tions with various clinical phenotypes ranging from simple type 2 (Th2) associated cytokines interleukin-4 (IL-4) and in-
chronic bronchitis without airflow obstruction to chronic ob- terleukin-5 (IL-5) (6) can also occur in chronic bronchitis, not
structive pulmonary disease (COPD) with mild to severe de- only in asthma, and that a marked upregulation of the eosino-
grees of airway obstruction and emphysema. In addition, air- phil chemoattractant RANTES (regulated upon activation,
way hyperreactivity may be present. Traditionally, based on normal T-cell expressed and secreted) in the epithelium and
simple sputum investigations, the airway inflammation of subepithelium most likely accounted for the increased eosino-
COPD was thought to be dominated by neutrophils, in con- philia. Where is now the distinction between a patient with
trast to asthma with eosinophils as pivotal effector cells. Does bronchitis and one with asthma? Is inflammation the same for
this still hold true? both diseases? Before reaching such a strong conclusion, sev-
When interpreting studies on airway inflammation, several eral issues should be taken into consideration.
issues need to be considered in order to understand possible dif- First, there is the general limitation regarding data from a
ferences in results. These include the different techniques ap- cross-sectional study. The investigators compared three groups
plied (biopsy versus bronchoalveolar lavage [BAL] versus in- of nonatopic subjects: healthy nonsmokers with normal lung
duced sputum), the different compartments investigated (central function, nonasthmatic smokers with chronic bronchitis and
versus peripheral airways versus lung parenchyma), the differ- mild airflow limitation in a stable phase of their disease (their
ent layers of the airway walls (subepithelial mucosa versus epi- mean FEV1 was 75% predicted), and nonasthmatic smokers
thelium versus the intraluminal space), or different stages or with chronic bronchitis who sought medical advice for an ex-
phases of the disease (asymptomatic versus simple chronic bron- acerbation (their mean FEV1 was 61% predicted). Thus, it is
chitis versus COPD versus emphysema; stable phase versus ex- not clear whether there was not a baseline difference in the
acerbation). Nevertheless, the message which emerged from group studied during exacerbation, regarding their profile of
these investigations of the past 10 yr can briefly be summarized inflammatory cells and cytokines. Was this group character-
as follows: asymptomatic smokers show an accumulation of ized by an eosinophilic bronchitis already before the exacer-
cells in the alveolar spaces, mainly of macrophages with the bation occurred? Obviously, repeated bronchial biopsies aim-
characteristic smokers’ inclusions. Compared with asymptom- ing at a longitudinal investigation of individual changes are
atic smokers, those with symptoms and mild COPD have an in- invasive procedures which may be applied only reluctantly. Such
crease in CD8 T lymphocytes in central (1, 2) and peripheral serial studies would be more feasible with induced sputum
airways (3). Finally, those with severe COPD develop a promi- analysis, although the target cells are different (luminal cells in
nent neutrophilia in the subepithelium of the central airways as induced sputum versus epithelial and subepithelial location in
compared with asymptomatic smokers (4). biopsy). What could have been done in the present study,
Are exacerbations of chronic bronchitis characterized by however, to strengthen the data and to allow comparison with
specific features? In this issue of the Journal, Zhu and col- previously published induced sputum data, is a parallel analy-
leagues provide further evidence that an exacerbation of sis of induced sputum. Second, biopsies obtained during bron-
chronic bronchitis is associated with tissue eosinophilia (pp. choscopy access the central airways (surely an important site
109–116) (5). They performed immunohistology and in situ for asthma), but not the peripheral small airways which play a
4 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 164 2001
crucial role in the development of smoking-related bronchial Whether the subset of COPD patients with eosinophilic
inflammation, at least in the initial stage. Finally, Zhu and col- bronchitis and the so called “allergic profile” of inflammation
leagues do not provide data on possible airway hyperreactiv- during exacerbations should be the target for long-term treat-
ity, in terms of the PC20 response to methacholine challenge. ment with inhaled corticosteroids remains to be determined.
Those patients with bronchitis and exacerbations may have Patients with COPD who show a response to oral corticoste-
had associated bronchial hyperreactivity, i.e., an “asthmatic roids have increased BAL eosinophilia (9). In COPD associ-
component” of their diseases, which might have accounted, at ated with eosinophilic bronchitis, inhaled corticosteroids im-
least partially, for the observed tissue eosinophilia. proved FEV1 and reversed the eosinophilia, but did not
Is “allergic profile” of inflammation the correct term for change the neutrophils (10). In summary, further studies of
the findings in this study? There are some arguments against the type presented by Zhu and colleagues in this Journal are
this. First, the Th2 cytokines IL-4 and IL-5 were expressed in definitely needed to improve our understanding of the under-
all individuals to the same degree, without significant differ- lying pathophysiology and to elucidate potential treatment
ence between the groups, including the healthy nonsmokers. modalities in the complex disease labeled COPD.
This may indicate that the cytokines are constitutively ex- ULRICH COSTABEL, M.D.
pressed, and that other stimuli are responsible for the eosino-
philia. Second, an eosinophilia is not exclusively related or Department of Pneumology/Allergy
synonymous to an “allergic profile”; a good example is idio- Ruhrlandklinik
pathic pulmonary fibrosis with increase in eosinophils in BAL Essen, Germany
fluid, but without known allergic mechanism.
The most striking finding associated with an exacerbation
was the upregulation of RANTES in both inflammatory and References
epithelial cells. The discussion of this finding is very sound, 1. O’Shaughnessy TC, Ansari TW, Barnes NC, Jeffery PK. Inflammation
with strong emphasis on viral infections as the most likely in bronchial biopsies of subjects with chronic bronchitis: inverse rela-
tionship of CD8 T lymphocytes with FEV1. Am J Respir Crit Care
cause of RANTES upregulation, and the synergistic function Med 1997;155:852–857.
of CD8 cytolytic cells to enhance the reaction of a FAS- 2. Lams BEA, Sousa AR, Rees PJ, Lee TH. Subepithelial immunopathol-
ligand-dependent apoptosis of virally infected cells (7). By this ogy of the large airways in smokers with and without chronic obstruc-
mechanism relapsing exacerbations due to viral infections tive pulmonary disease. Eur Respir J 2000;15:512–516.
may pave the way for chronic bronchitis to permanent tissue 3. Saetta M, Di Stefano A, Turato G, Facchini FM, Corbino L, Mapp CE,
damage and may accelerate the decline in lung function. Maestrelli P, Ciaccia A, Fabbri LM. CD8 T-lymphocytes in the pe-
ripheral airways of smokers with chronic obstructive pulmonary dis-
CD8 cells seem to be important already early in the patho- ease. Am J Respir Crit Care Med 1998;157:822–826.
genesis of COPD. Saetta and associates showed that smokers 4. Di Stefano A, Capelli A, Lusuardi M, Balbo P, Vecchio C, Maestrelli P,
with mild COPD had greater numbers of CD8 cells in pe- Mapp CE, Fabbri LM, Donner CF, Saetta M. Severity of airflow limi-
ripheral airways than asymptomatic smokers, whereas the tation is associated with severity of airway inflammation in smokers.
other inflammatory cells, including neutrophils, were similar Am J Respir Crit Care Med 1998;158:1277–1285.
(3). In contrast, activated CD4 cells are the predominant 5. Zhu J, Qiu YS, Majumdar S, Gamble E, Matin D, Turato G, Fabbri LM,
Barnes N, Saetta M, Jeffery PK. Exacerbations of bronchitis: bron-
T-cell subsets in airways of asthmatics (8). chial eosinophilia and gene expression for IL4, IL 5, and eosinophil
Do these findings apply to all exacerbations of COPD? Vi- chemoattractants. Am J Respir Crit Care Med 2001;164:109–116.
ruses are important triggers of COPD exacerbations, but some 6. Mackay IR, Rosen FS. Advances in immunology: asthma. N Engl J Med
exacerbations may be triggered by bacterial infections. Other 2001;5:344–362.
possible triggers may be inhaled allergens or chemical sensitiz- 7. Hadida F, Vieillard V, Mollet L, Clark-Lewis I, Baggiolini M, Debre P.
ers, which would likely be also associated with eosinophilia. In Cutting edge: RANTES regulates Fas ligand expression and killing by
HIV-specific CD8 cytotoxic T cells. J Immunol 1999;161:1105–1109.
exacerbations caused by bacterial infection, however, one would 8. Assawi M, Bradley B, Jeffery PK, Frew AJ, Wardlaw AJ, Knowles G,
expect no tissue eosinophilia and no allergic profile, but in- Assoufi B, Collins JV, Durham S, Kay AB. Identification of activated
stead an increase in neutrophils and upregulation of IL-8 as an T lymphocytes and eosinophils in bronchial biopsies in stable atopic
important neutrophil chemoattractant. We have no informa- asthma. Am J Respir Crit Care Med 1990;142:1407–1413.
tion from Zhu and colleagues about the number of neutro- 9. Chanez P, Vignola AM, O’Shaugnessy T, Enander I, Li D, Jeffery PK,
phils and the expression of IL-8 in the bronchial mucosa of Bousquet J. Corticosteroid reversibility in COPD is related to fea-
tures of asthma. Am J Respir Crit Care Med 1997;155:1529–1534.
their patients. Further investigations of similar type in patients 10. Pizzichini E, Pizzichini MMM, Gibson P, Parameswaran K, Gleich GJ,
with COPD should analyze neutrophils and neutrophil-re- Berman L, Dolovich J, Hargreave FE. Sputum eosinophilia predicts
lated mediators and cytokines as well, and also try to probe for benefit from prednisone in smokers with chronic obstructive bronchi-
the presence of viruses or bacteria. tis. Am J Respir Crit Care Med 1998;158:1511–1517.