Chest ACCP Member Benefits
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (30)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pérez-Guzmán, C.
Right arrow Articles by Villarreal-Velarde, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pérez-Guzmán, C.
Right arrow Articles by Villarreal-Velarde, H.
(Chest. 1999;116:961-967.)
© 1999 American College of Chest Physicians

Does Aging Modify Pulmonary Tuberculosis?*

A Meta-Analytical Review

Carlos Pérez-Guzmán, MD; Mario H. Vargas, MD, MS, FCCP; Alfredo Torres-Cruz, MD and Héctor Villarreal-Velarde, MD

* From the Instituto Nacional de Enfermedades Respiratorias (Drs. Vargas, Pérez-Guzmán, and Torres-Cruz), the Hospital General "Manuel Gea González" (Dr. Villarreal-Velarde) and the Departamento de Neumología, Hospital General del CMN La Raza (Dr. Pérez-Guzmán), Instituto Mexicano del Seguro Social, México DF, México.

Correspondence to: Dr. Mario H. Vargas, Instituto Nacional de Enfermedades Respiratorias, Tlalpan 4502, CP 14080, México DF, México; e-mail: mhvargas{at}mailer.main.conacyt.mx


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objectives: To evaluate the differences in the clinical, radiologic, and laboratory features of pulmonary tuberculosis (TB) in older patients, as compared to younger patients.

Design: A meta-analysis (the Schmidt-Hunter method) of published works found in MEDLINE and other sources was performed. A total of 12 studies were collected, and each variable was submitted to meta-analysis.

Results: No differences were found between older (>= 60 years old) and younger TB patients with respect to male predominance, evolution time before diagnosis, prevalence of cough, sputum production, weight loss, fatigue/malaise, radiographic upper lobes lesions, positive acid-fast bacilli in sputum, anemia or hemoglobin level, and serum aminotransferases. A lower prevalence of fever, sweating, hemoptysis, cavitary disease, and positive purified protein derivative, as well as lower levels of serum albumin and blood leukocytes were noticed among older patients. In addition, the older population had a greater prevalence of dyspnea and some concomitant conditions, such as cardiovascular disorders, COPD, diabetes, gastrectomy history, and malignancies.

Conclusions: This meta-analytical review identified the main differences of older TB patients, as compared to younger TB patients, that should be considered during the diagnostic evaluation. Most of these differences are explained by the already known physiologic changes that occur during aging.

Key Words: aging • comparative study • elderly • meta-analysis • pulmonary tuberculosis


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Pulmonary tuberculosis (TB) represents an important worldwide health problem. It has been reported by the World Health Organization that one person in the world becomes infected every second, and that one third of the entire population of the world is now infected.1 The World Health Organization also estimates that in the next decade, 300 million more people will be infected, 90 million people will develop the disease, and 30 million people will die from it.1

Older subjects represent a population at a special high risk for developing the disease. This is demonstrated by the fact that in 1996 in the United States, pulmonary TB affected 11.5/100,000 subjects >= 65 years old, whereas for the general population, the rate was only 6.0/100,000 subjects.2 In Mexico, the incidence rate of pulmonary TB in 1994 was 14.9/100,000 subjects for the general population and 45.8/100,000 for subjects >= 65 years old.3 In addition, older people that live in nursing homes are at a special high risk for developing pulmonary TB, as are those on naval vessels, and those in prisons, jails, mental hospitals, chronic disease hospitals, juvenile detention facilities, and shelters for the homeless.4 In American nursing homes, the TB rate for men (1,000/100,000) and for women (376/100,000) is notably higher than the nationwide prevalence.5

It has been suggested that the characteristics of TB in older people are different from those observed in young adult patients, and that they should be classified as separate entities.6 7 Accordingly, it has also been suggested that when these differences are ignored, the establishment of a diagnosis may be delayed, leading to an increase in morbidity and mortality in the older group.8 Although several published works have looked for differences between younger and older tuberculous patients, they usually provide quite discordant findings.9 10 11 12 13 14 15 16 17 18 19 20 Thus, the controversy on this matter is still present. Therefore, in order to clarify this issue, a meta-analysis of published studies comparing pulmonary TB in older and younger patients was performed.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
A search for comparative studies related to pulmonary TB in older and younger subjects was made in June 1998 using the entire MEDLINE database (from 1966 to 1998) through the Internet site of the National Library of Medicine (http://www.ncbi.nlm.nih.gov). The terms "pulmonary TB AND (aged OR aging OR old OR older OR elder OR elderly)" appearing in any field of the database records retrieved 7,440 articles. Further searching for "comparative OR comparison OR compared" in any field yielded 1,011 articles. From these studies, we selected those articles in which the record suggested that a comparison of clinical, radiologic, or routine laboratory tests was done, and the full article was obtained. Additional national and international journals in which articles on this subject might have been published were also reviewed. From these publications, articles were selected in which an original research study was actually performed comparing older and younger tuberculous populations. We obtained a total of 13 articles, 1 of which was discarded because most of its patients were included in a subsequent publication that was already included in our review. Thus, a final total of 12 articles were considered for the present work. The meta-analytical evaluation of each variable of interest was performed through data transformation to effect sizes r, and then the Schmidt-Hunter method (using Fisher's z transformation) was applied (Meta-Analysis Programs v5.3; Ralf Schwarzer; Berlin, Germany). In addition to the effect sizes ± 95% confidence intervals, the fail-safe N, a term that indicates how many unpublished no-effect studies would have to exist in the file drawers in order to invalidate the overall significance of the result, was also calculated.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
As can be seen in Table 1 , all of the studies included inpatients in their populations, while outpatients were also included in half of them. The pooled number of patients was comprised of a total population of 859 older and 1,801 younger patients. There was a noticeable variability in the results obtained by these studies, both in the clinical features and the auxiliary tests (Table 2 ), as well as in the radiologic findings (Table 3 ). Because many variables were not uniformly present in all of the studies, differences in the final number of articles taken into account for the meta-analytical assessment of each variable were obtained.


View this table:
[in this window]
[in a new window]

  		Table 1. Comparative Studies on the Differences Between Younger and Older Patients With Pulmonary TB*

 

View this table:
[in this window]
[in a new window]

  		Table 2. Differences Between Younger and Older Patients With Pulmonary TB*

 

View this table:
[in this window]
[in a new window]

  		Table 3. Radiological Differences Between Younger and Older Patients With Pulmonary TB*

 
Figure 1 shows the results of meta-analysis with respect to gender, evolution time, and concomitant conditions. For the evaluation of gender, two articles containing this data were not included in the analysis because these studies were of war veterans, and thus a strong bias toward the inclusion of male patients was present. According to the male/female ratios (Table 2) , a male predominance was observed in all studies reporting this data. The meta-analysis, however, showed that this male predominance was similar in both younger and older tuberculous populations. Although the meta-analysis yielded statistical significance for a greater evolution time (p < 0.05) in older patients as compared to younger patients, this difference was rather mild, according to the low fail-safe N obtained for this variable. The prevalence of concomitant conditions, such as cardiovascular disorders, COPD, diabetes, gastrectomy history, and malignancies was higher in older patients (p < 0.05 to p < 0.01), while alcoholism was more frequently seen in younger patients (p < 0.01). Other conditions, such as immunosupressor therapy, pneumoconiosis, and tobacco smoking showed no statistical differences in both groups.



View larger version (23K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1. Meta-analysis of comparative studies between younger and older tuberculous patients, regarding gender, evolution time, and associated conditions. *p < 0.05; **p < 0.01.

 
In relation to the clinical findings (Fig 2 ), a lower prevalence of fever, sweating, and hemoptysis (p < 0.01), as well as a higher prevalence of dyspnea (p < 0.01), were found in older patients, as compared to younger patients. Radiographic images of cavitation were more frequently found in young patients. Although findings of positive acid-fast bacilli (AFB+) in sputum smear was significantly more common in older subjects (p < 0.05), this statistical significance was negligible, since the 95% confidence interval range crosses through zero effect size, and fail-safe N was not required to counterbalance the significance. Lower albumin levels and lower total leukocyte counts were found more commonly among older patients (p < 0.01). Finally, the tuberculin skin test was less frequently positive in older patients (p < 0.01). The remaining variables (cough, sputum production, weight loss, fatigue/malaise, upper lobes involvement, anemia or low hemoglobin, and levels of serum aspartate aminotransferase and alanine aminotransferase) were not different in both groups.



View larger version (29K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2. Meta-analysis of comparative studies between younger and older tuberculous patients, regarding symptoms, radiologic images, and laboratory findings. Hb=hemoglobin; ALT=alanine aminotransferase; AST=aspartate aminotransferase. *p < 0.05; **p < 0.01.

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
In this work, a meta-analytical review was performed of the main clinical, radiologic, and laboratory features of TB in older patients, as compared to younger patients. In relation to the gender of the patients, we found that male predominance was consistently described by most of the analyzed reported series, and the magnitude of this predominance, as indicated by the meta-analysis, was not different between younger and older patients. The reason for the higher frequency of TB in male subjects at any age has not been sufficiently addressed. One possible explanation for this gender difference is that in most countries, young men usually have more social and labor activities than women, thus favoring the transmission of the disease. This hypothesis is in agreement with the higher prevalence of positive tuberculin test result in male subjects than in female subjects.21 22 This higher rate of infection in young men could determine the higher frequency of the development of symptomatic TB in this gender. However, the presence of a biological factor conferring protection against infection and/or clinical development of TB in female subjects cannot be precluded, and deserves further investigation.

Some reports have described a delay in the diagnosis of TB in older patients, mainly due to an atypical presentation of the disease 23 24 and/or to the lower awareness of the disease among this population.25 However, we did not corroborate such a delay, since the meta-analysis showed that the time elapsed from the beginning of symptoms to the establishment of a diagnosis was very similar in older and younger patients. This conclusion is also supported by the work of Asch et al, 26 who recently found that neither age nor the presence of serious symptoms were involved in the delay in seeking medical care among tuberculous patients.

The greater prevalence of certain concomitant conditions in the older group was not a surprising finding, since such conditions are usually more frequently seen among elderly people, independently of TB. This was the case for cardiovascular disorders, COPD, diabetes, and neoplasms, which in our meta-analysis were more prevalent in older subjects. Although many studies that were included in the meta-analysis considered these and other concomitant conditions as if they were risk factors for the development of TB, the design of such studies did not allow them to evaluate whether these conditions constitute true risk factors, because none of the studies included control nontuberculous groups. Therefore, we were only able to determine whether a condition was more frequently observed in younger or older patients, without trying to determine if a cause/effect relationship exists.

Several clinical manifestations presented differences between the younger and older patients. Fever was less frequently observed in older subjects, which is in full agreement with the well-established knowledge that mammals, including human beings, have a decreased pyrogenic response when aging. Proposed mechanisms for this higher fever threshold are a decrease in the responsiveness of the hypothalamic thermoregulatory center to prostaglandin E2 (released by interleukin 1),27 or an increased sensitivity to natural antipyretics, such as {alpha}-melanocyte stimulating hormone.28 The lower prevalence of sweating in the older patients is likely related to the lower presence of fever.

Dyspnea was more frequent among older patients, which can be explained mainly by the expected decrease in pulmonary function with aging.29 For example, in a healthy 72-year-old nonsmoking subject, the FEV1 should be around 1,300 mL lower than in a 35-year-old subject, ie, a 32% loss of FEV1 will have occurred in this period. However, many other changes occurring with aging in organs other than the lung, such as the cardiovascular system, can also be partially involved in the production of dyspnea.

The higher prevalence of hemoptysis in young tuberculous patients was probably related to the higher frequency of lung cavitation in this population. In this sense, the presence of distorted ectatic blood vessels (Rassmusen's aneurysms) in the wall of lung cavitation was described a long time ago as the main cause of massive hemoptysis.30 31 Thus, it is probable that these vessels could account for the increased prevalence of blood in sputum.

Some of the observed differences between younger and older patients may be related to a decrease in the immunologic status associated with aging. It is well known that older people have an impaired T-lymphocyte function, including the proliferative response,32 which can account for the lower number of leukocytes found in our meta-analysis. Moreover, impairment of the immunologic responses of T lymphocytes can explain the lower frequency of positive tuberculin skin tests (PPD+) in older patients. The relationship of abnormalities of the immune function in elderly patients to the slightly higher prevalence of mycobacterial detection (AFB+) in this population needs to be further investigated.

With respect to radiologic images, and in close relationship with the poorer immunologic status, lung cavitation was less frequently seen in older patients. This lower frequency of cavitation has also been documented in other immunocompromised patients, such as those HIV-positive subjects with associated TB.33 Several works have reported atypical radiologic images of tuberculous lesions in older patients, suggesting that pulmonary lesions occur more often in lower lung fields.10 11 14 20 Due to the high variability in the radiologic description of images in the analyzed studies, we could not analyze all of the possibilities. The only finding that was reported in almost all of the studies was upper lobe lesions. The frequency of upper lobe lesions was not different in either group after the meta-analysis was done. Nevertheless, this does not exclude the presence of atypical radiologic images in the lower lung fields, in addition to the typical radiologic images.

Serum albumin concentration was lower in older tuberculous patients. This could lead to the speculation that older persons suffer from malnutrition more frequently than younger people, perhaps due to the poorer personal care that is received by older persons. Nevertheless, it is interesting to note that anemia, another parameter of malnutrition, was found with similar frequency in both groups. In addition, it has been shown that even in healthy subjects, serum albumin levels decrease with aging.34 35 Thus, the finding of a lower albumin level in older subjects might reflect not only malnutrition, but also the expected decrease of albumin during aging.

In conclusion, this meta-analytical review identified some differences in older tuberculous patients in comparison to younger ones: a lower prevalence of fever, sweating, hemoptysis, cavitary disease, and PPD+, as well as lower levels of serum albumin and blood leukocytes. In contrast, this population had a higher prevalence of dyspnea. These differences in the TB presentation could be explained by the already known physiologic changes that occur with aging, but they must be kept in mind during the diagnostic evaluation. As expected, older tuberculous patients had more prevalence of some morbid concomitant conditions, such as cardiovascular disorders, COPD, diabetes, gastrectomy history, and malignancies.


   Footnotes
 
For editorial comment see page 856.

Abbreviations: AFB+ = positive acid-fast bacilli; TB = tuberculosis; PPD+ = positive purified protein derivative

Received for publication December 8, 1998. Accepted for publication May 7, 1999.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. World Health Organization. Tuberculosis. Fact sheet No. 104 (revised). Available at: http://www.who.ch/. Accessed March 1996
  2. Centers for Diseases Control. Tuberculosis surveillance and census data. Available at: http://wonder.cdc.gov/. Accessed
  3. Dirección General de Epidemiología, SSA. Bol Epidemiol 1994
  4. Stead, WW (1989) Special problems in tuberculosis: tuberculosis in the elderly and in residents of nursing homes, correctional facilities, long-term care hospitals, mental hospitals, shelters for the homeless, and jails. Clin Chest Med 10,397-405[ISI][Medline]
  5. Stead, WW, Logfren, JP, Warren, E, et al (1985) Tuberculosis as an endemic and nosocomial infection among the elderly in nursing homes. N Engl J Med 312,1483-1487[Abstract]
  6. Morris, CDW (1989) The radiography, hematology and biochemistry of pulmonary tuberculosis in the aged. Q J Med 71,529-535[Abstract/Free Full Text]
  7. Morris, CDW (1990) Pulmonary tuberculosis in the elderly: a different disease? Thorax 45,912-913[ISI][Medline]
  8. Rieder, HL, Kelly, GD, Bloch, AD, et al (1991) Tuberculosis diagnosed at death in the United States. Chest 100,678-681[Abstract/Free Full Text]
  9. Alvarez, S, Shell, C, Berk, SL (1987) Pulmonary tuberculosis in elderly men. Am J Med 82,602-606[CrossRef][ISI][Medline]
  10. Katz, PR, Reichman, W, Dube, D, et al (1987) Clinical features of pulmonary tuberculosis in young and old veterans. J Am Geriatr Soc 35,512-515[ISI][Medline]
  11. Umeki, S (1989) Comparison of younger and elderly patients with pulmonary tuberculosis. Respiration 55,75-83[ISI][Medline]
  12. Tsai, SY, Huang, MS, Hwang, JJ, et al (1991) Comparison of pulmonary tuberculosis in younger and elderly patients. Kao-Hsiung I Hsueh K'o Hsueh Tsa Chih 7,107-114
  13. Van den Brande, P, Vijgen, J, Demedts, M (1991) Clinical spectrum of pulmonary tuberculosis in older patients: comparison with younger patients. J Gerontol 46,M204-M209[ISI][Medline]
  14. Teale, C, Goldman, JM, Pearson, SB (1993) The association of age with the presentation and outcome of tuberculosis: a five-year survey. Age Aging 22,289-293[Abstract/Free Full Text]
  15. Korzeniewska-Kosela, M, Krysl, J, Müller, N, et al (1994) Tuberculosis in young adults and the elderly: a prospective comparison study. Chest 106,28-32[Abstract/Free Full Text]
  16. Chan, CHS, Woo, J, Or, KKH, et al (1995) The effect of age on the presentation of patients with tuberculosis. Tubercle Lung Dis 76,290-294[CrossRef][ISI][Medline]
  17. Liaw, YS, Yank, PC, Yu, CJ, et al (1995) Clinical spectrum of tuberculosis in older patients. J Am Geriatr Soc 43,256-260[ISI][Medline]
  18. Zamarron, C, Salgueiro, M, Alvarez, JM, et al (1997) Características clínicas de la tuberculosis pulmonar en el anciano. An Med Interna 14,167-169[Medline]
  19. Rocha, M, Pereira, S, Barros, H, et al (1997) Does pulmonary tuberculosis change with aging? Int J Tuberc Lung Dis 1,147-151[ISI][Medline]
  20. Villarreal-Velarde, H, Vargas, MH, Torres-Cruz, A, et al (1998) Tuberculosis pleuropulmonar en el anciano: estudio comparativo con otras edades Rev Inst Nal Enf Respir (Mex) 11,111-116
  21. Stead, WW, To, T (1987) The significance of the tuberculin test in elderly persons. Ann Intern Med 107,837-842
  22. Bener, A (1990) Prevalence of tuberculosis infection in Abha and Baha. Eur J Epidemiol 6,376-381[CrossRef][ISI][Medline]
  23. Enarson, DA, Grzybowski, S, Dorken, D (1978) Failure of diagnosis as a factor in tuberculosis mortality. Can Med Assoc J 118,1520-1522[Abstract]
  24. Katz, I, Rosenthal, T, Michael, D (1985) Undiagnosed tuberculosis in hospitalized patients. Chest 87,770-776[Abstract/Free Full Text]
  25. Dutt, AK, Stead, WW (1993) Tuberculosis in the elderly. Med Clin North Am 77,1353-1367[ISI][Medline]
  26. Asch, S, Leake, B, Anderson, R, et al (1998) Why do symptomatic patients delay obtaining care for tuberculosis? Am J Respir Crit Care Med 157,1244-1248[Abstract/Free Full Text]
  27. Wakefield, KM, Henderson, ST, Streit, JG (1989) Fever of unknown origin in the elderly. Prim Care 16,501-513[ISI][Medline]
  28. Murphy, MT, Lipton, JM (1982) Peripheral administration of alpha-MSH reduces fever in older and younger rabbits. Peptides 3,775-779[CrossRef][ISI][Medline]
  29. Snider, GL, Faling, LJ, Rennard, SI (1994) Chronic bronchitis and emphysema. Murray, JF Nadel, JA eds. Textbook of respiratory medicine ,1342 WB Saunders Philadelphia, PA.
  30. Auerbach, O (1939) Pathology and pathogenesis of pulmonary arterial aneurysms in tuberculous cavities. Am Rev Tuberc 40,99-105
  31. Middleton, JR, Sen, P, Lange, M, et al (1977) Death-producing hemoptysis in tuberculosis. Chest 72,601-604[Abstract/Free Full Text]
  32. Ben-Yehuda, A, Weksler, ME (1994) Host resistance and the immune system. Clin Geriatr Med 8,701-711
  33. Friedman, LN, Selwyn, PA (1994) Pulmonary tuberculosis: primary, reactivation, HIV related, and non-HIV related. In Friedman LN, ed. Tuberculosis: current concepts and treatment. ,93-112 CRC Press Boca Raton, FL.
  34. Shibata, H, Haga, H, Ueno, M, et al (1991) Longitudinal changes of serum albumin in elderly people living in the community. Age Aging 20,417-420[Abstract/Free Full Text]
  35. Walker, AR, Walker, BF, Manetsi, B, et al (1991) Serum albumin levels in elderly rural Africans. Int J Vitam Nutr Res 61,339-345[ISI][Medline]



This article has been cited by other articles:


Home page
 ChestHome page
N. N. Hansel, B. Merriman, E. F. Haponik, and G. B. Diette
Hospitalizations for Tuberculosis in the United States in 2000: Predictors of In-Hospital Mortality
Chest, October 1, 2004; 126(4): 1079 - 1086.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
C. PEREZ-GUZMAN, A. TORRES-CRUZ, H. VILLARREAL-VELARDE, and M. H. VARGAS
Progressive Age-related Changes in Pulmonary Tuberculosis Images and the Effect of Diabetes
Am. J. Respir. Crit. Care Med., November 1, 2000; 162(5): 1738 - 1740.
[Abstract] [Full Text]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (30)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pérez-Guzmán, C.
Right arrow Articles by Villarreal-Velarde, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pérez-Guzmán, C.
Right arrow Articles by Villarreal-Velarde, H.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS