Tài liệu Manifestations of Pulmonary Tuberculosis in the Elderly: A Prospective Observational Study from North India pptx

Manifestations of Pulmonary Tuberculosis in the Elderly: A Prospective Observational Study from North India Dheeraj Gupta1, Navneet Singh1, Ravinder Kumar2 and Surinder K.. The aim of th

[Received: May 7, 2007; accepted after revision: November 5, 2007]

Correspondence and reprint requests: Dr Dheeraj Gupta, Additional Professor, Department of Pulmonary Medicine, Post Graduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh-160 012, India; Phone: 91-172-2756823; Fax: 91-172-2748215, 91-172-2745959; E-mail: dheeraj@indiachest.org

Manifestations of Pulmonary Tuberculosis in the Elderly:

A Prospective Observational Study from North India

Dheeraj Gupta1, Navneet Singh1, Ravinder Kumar2 and Surinder K Jindal1

Departments of Pulmonary Medicine1 and Internal Medicine2, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

ABSTRACT Background. There is scarcity of published literature on manifestations of pulmonary tuberculosis (PTB) among elderly patients in India The aim of the present study was to compare the clinical, radiological and laboratory manifestations of PTB among young and elderly patients

Methods. This prospective study involved 100 human immunodeficiency virus (HIV) negative patients with PTB The demographic, clinical, radiological and laboratory manifestations were compared between young (n=50; under 60 years of age) and elderly (n=50; aged 60 years and above) with PTB

Results. Elderly patients, in comparison to younger patients, tended to be heavier smokers and had more co-morbidities

(40% vs 8%; p < 0.05) They presented more frequently with constitutional symptoms (except fever) and less frequently with

respiratory symptoms The mean duration of symptoms and rate of sputum smear-positivity for acid-fast bacilli was similar

in both groups Both the groups were similar with respect to physical examination and chest radiograph findings Median values of erythrocyte sedimentation rate and total leukocyte count were significantly higher and lower respectively in the elderly patients

Conclusions The presentation of PTB in elderly patients differs from that of younger patients by the predominance of constitutional rather than respiratory symptoms A high index of suspicion is required to make a timely diagnosis of tuberculosis in the elderly [Indian J Chest Dis Allied Sci 2008; 50: 263-267]

Key words: Constitutional, Elderly, Pulmonary, Respiratory, Symptoms, Tuberculosis.

INTRODUCTION

Tuberculosis (TB) remains a major challenge for

health-care workers throughout the world despite major

progress in the development of new strategies for its

diagnosis and treatment In elderly patients, the clinical

and radiological presentations are often nonspecific,

leading to a delay in diagnosis and in initiating

appropriate treatment, which often results in a

significant proportion of cases being discovered at

autopsy only.1 There is scarcity of published literature

on manifestations of TB especially pulmonary

tuberculosis (PTB) among elderly patients from India

The aim of the present study was to compare the

clinical, radiological and laboratory manifestations of

PTB among elderly patients (above the age of 60 years)

with those in young patients (below the age of 60 years)

MATERIAL AND METHODS

This prospective study involved a total of 100 human

immunodeficiency virus (HIV) negative patients with

PTB Elderly (n=50; Group I; aged 60 years and above) and young (n=50; Group II; under 60 years) patient were

selected from those being treated as out-patients (at the Chest Clinic) or in-patients (admitted to any of the wards) at Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh Patients with PTB in whom sputum smear revealed acid-fast bacilli

(AFB) and/or culture grew Mycobacterium tuberculosis were included Patients who were sputum

smear-negative for AFB and in whom the diagnosis of PTB was established on the basis of clinical and radiological features consistent with TB and a good clinical response

to antituberculosis treatment (ATT) were also enrolled

in the study.2 The study alsoincluded patients with PTB

who had concomitant evidence of extrapulmonary TB (EPTB) The diagnosis of EPTB was based on clinical

and radiological features suggestive of TB concerning

the involved site with supportive evidence in the form

of demonstration of AFB and/or granulomas/caseous necrosis from specimens obtained from the affected site

Patients who were HIV seropositive, those on

immunosuppressive drugs or with underlying

haematological malignancies, were excluded from the

study

All patients underwent a detailed clinical evaluation

Details noted included history of fever, constitutional or

respiratory symptoms, duration of symptoms, duration

and quantity of tobacco smoking, past medical and

treatment history Tobacco smoking was further

categorised after calculation of smoking index (the

product of the number of cigarettes/bidis smoked per

day and the number of years for which they had been

smoked) All patients underwent haematological

(complete hemogram) and biochemical (liver and renal

function tests, fasting and post-prandial blood sugar

testing) laboratory tests and a chest radiograph

Serological testing for HIV was conducted at the

Voluntary Counselling and Testing Centre (VCTC)

located within PGIMER, Chandigarh after taking

informed consent from the patients All patients had

three consecutive sputum smears examined for the

presence of AFB using Ziehl-Neelsen technique This

was done as per recommendations of the Revised

National Tuberculosis Control Programme (RNTCP),

Government of India at the Designated Microscopy

Centre (DMC) located within PGIMER, Chandigarh

Sputum induction was attempted in patients who were

not producing sputum spontaneously The study was

cleared by the ethics committee of the Institute

Informed consent was taken for each subject

Statistical Analysis

Quantitative and qualitative data are expressed as

median [inter-quartile (IQ) range] and percentages

respectively Quantitative variables were compared

using Mann-Whitney U test while qualitative variables

were compared using Pearson Chi-square test A ‘p’

value of less than 0.05 was considered significant

RESULTS

The demographic characteristics of patients in the two

groups are shown in table 1 Although male

predominance was seen in both the groups, there was

no difference in the gender distribution Patients in

Group I tended to be heavier smokers compared to those

in Group II; the percentage of patients having a smoking

index of more than 300 being 30% and 2% respectively

(p<0.05) A significant percentage of elderly patients

(40%) had chronic diseases and were on long-term

medication for the same (32%); the most common

co-morbid illness being diabetes mellitus (16%)

Isolated PTB was the most common presentation

(86% and 82% in Groups I and II respectively) Among

patients with PTB who also had EPTB, the most

common site of extra pulmonary involvement was

Table 1 Demographic characteristics of elderly (Group I) and young (Group II) patients with pulmonary tuberculosis

(≥≥≥≥≥ 60 years) (< 60 years) (n = 50) (n = 50)

No (%) No (%)

Mean age + SD (years)* 63.1 ± 3.9 30.2 ± 9.4 Smokers : Non-smokers 21 : 29 18 : 32 Smoking index

Presence of chronic disease(s) 20 (40) 4 (8)

Use of regular medication(s) for 16 (32) 2 (4) chronic disease(s)

*p < 0.05; ATT = Antituberculosis treatment COPD = Chronic obstructive pulmonary disease CAD = Coronary artery disease, CRF = Chronic renal failure.

lymph nodes (n=3, in Group I; n=5 in Group II) None of

the observed differences (Table 2) between the two groups with respect to extrapulmonary involvement were statistically significant

Comparison of the clinical features among patients in both groups is presented in table 2 Elderly patients, in comparison to younger patients, presented more frequently with constitutional symptoms and less frequently with respiratory symptoms The duration of symptoms prior to diagnosis was similar (median 2; IQ range 1-5 weeks) in elderly and young patients Rate of sputum smear-positivity for AFB was also similar in

Groups I and II [29/41 (70.7%) vs 35/48 (72.9%)

respectively] Seven patients in Group I and five in Group

II who did not report with sputum production initially

could provide an adequate sample for testing following sputum induction There was no significant difference

in the two groups with respect to findings on the chest radiograph (Table 3)

Elderly patients (Group I), in comparison to younger patients (Group II), had higher median (IQ range) values

of erythrocyte sedimentation rate (ESR) [49 (35-64) vs 32

(16-55) mm at the end of the first hour] and lower mean values of total leucocyte count (TLC) [7000 (6000-8800)

vs 8100 (6200-11600) mm/µL] Other haematological

and biochemical results were similar in both the groups

DISCUSSION

Tuberculosis is becoming increasingly common in the elderly and burden of the disease in them is likely to continue to increase substantially.3,4 Moreover, with increasing age, a state of relative deficiency develops as

a result of a reduction in the number and function of the T-helper lymphocytes and an increase in the presence of T-suppressor cells This decline in natural immunity enhances the possibility of endogenous reactivation of

infection by Mycobacterium tuberculosis bacilli and the

development of active TB.5 Pulmonary tuberculosis is the most common form of TB even in the elderly although EPTB is more frequently seen than in the young.6,7

Presentation of PTB in the elderly often differs from that in younger patients and some authors have even suggested that PTB in the elderly may even be considered as a distinct disease entity.8 These differences can lead to a delay in the diagnosis of TB in the elderly, which in turn, can lead to an increase in the morbidity and mortality in them.9, 10

A recent meta-analysis11 of 12 published studies sought to compare the clinical, radiological and laboratory features of PTB among older and younger patients This meta-analysis11 did not reveal any significant difference between the two groups with respect to male preponderance, evolution time before diagnosis, prevalence of certain respiratory symptoms (cough, sputum production), presence of upper lobe lesions on chest radiographs, detection rate of AFB in sputum, haemoglobin levels and serum aminotransferases However, several other clinical manifestations differed significantly between the younger and older patients Fever and sweating were observed less frequently among the older patients and this was attributed to the reduced pyrogenic response with ageing Dyspnoea was more prevalent in the elderly and this could be explained in part by the decline in pulmonary function that occurs with ageing Haemoptysis was less common among the elderly and correlated with the lower prevalence of cavitary disease Lower levels of serum albumin and blood leucocytes were noticed among older patients A higher prevalence

of co-morbid conditions like diabetes mellitus, cardiovascular disorders and chronic obstructive pulmonary disease was seen in the elderly TB patients These differences in the presentation of PTB among the elderly can thus be explained by well known physiological changes that are known to occur with ageing and hence must be kept in mind during the diagnostic evaluation of elderly patients.11

Several findings of the current study are in accordance with the results of this meta-analysis In the present study, male preponderance, mean duration of symptoms prior to diagnosis, rates of sputum smear AFB positivity and chest radiograph findings were similar in both the age groups Lower frequency of respiratory symptoms and fever, lower mean values of TLC as well as higher prevalence of chronic co-morbid illnesses in the elderly patients were also observed in the current study

However, certain findings of the current study differed from those of the meta-analysis11 and included

Table 3 Radiographic features in elderly (Group I) and young

(Group II) patients with pulmonary tuberculosis

(≥≥≥≥≥ 60 years) (< 60 years) (n = 50) (n = 50)

No (%) No (%)

Normal chest radiograph 3 (6) 6 (12)

Hilar lymph node enlargement 3 (6) 2 (4)

Pleural effusion/thickening 9 (18) 8 (16)

*Extensive fibrocavitary disease involving both lobes of one

lung that is associated with volume loss and tracheal/

mediastinal shift and with normal/near normal lung fields

on the opposite side.

Table 2 Clinical features in elderly (Group I) and young (Group

II) patients with pulmonary tuberculosis

(≥≥≥≥≥ 60 years) (< 60 years) (n = 50) (n = 50)

No (%) No (%)

Site of Involvement

Pulmonary and extrapulmonary TB 7 (14) 9 (18)

Respiratory Symptoms

Constitutional Symptoms

General Physical Examination

Respiratory System Examination

Bronchial breath sounds 10 (20) 12 (24)

Reduced intensity of breath sounds 9 (18) 13 (26)

*p < 0.05, TB = Tuberculosis.

a higher frequency of constitutional symptoms (other

than fever) in the elderly patients It is well known that

the clinical presentation of TB can often be atypical and

subtle in the elderly and that symptoms like

unexplained weight loss, “failure to thrive,” weakness

or a change in cognitive status may be the sole

manifestation of the disease.12 Recent retrospective

studies from Korea10 and Hong Kong13 have found

similar observations regarding an increase in the

presence of constitutional symptoms in elderly patients

with TB This results in a delay in the presentation of the

elderly to health care facilities, thereby resulting in a

delay in the commencement of ATT The delay in

presentation among elderly patients with TB has also

been documented previous study by Arora et al 14 from

Himachal Pradesh In that study,14 only 36.9% of

patients presented within three months of onset of

symptoms, while 41.2% presented after six months of

onset of symptom Most of the patients (78.1%) had

advanced disease radiologically at the time of

diagnosis.14

In the current study, a higher percentage of elderly

patients were heavy smokers (SI > 300) By virtue of

age, it is expected that elderly patients would have

smoked more However, heavy smoking is associated

with a relative risk of 2 to 4 for developing TB.5,15

Current smokers, in comparison with never-smokers,

have a higher risk of developing PTB but not EPTB.15

Furthermore, patients who develop TB tend to have

smoked more cigarettes per day than those who do

not.15 Leung and colleagues13 had observed that older

people with TB were more likely to smoke than younger

people with the disease Arora and colleagues had also

found that almost two thirds of their elderly patients

with TB were smokers (13.43 + 8.76 vs 10.96 + 7.87,

p=0.01) A statistically significant dose-response

relationship was observed with respect to smoking and

active TB (p < 0.05) and culture-confirmed TB (p < 0.05)

A recent review16 that looked at the available

evidence on the association between smoking and

various TB outcomes stated that there is considerable

evidence to suggest that tobacco smoking is associated

with TB The evidence was stronger for TB disease than

for TB infection or for mortality related to TB But since

the magnitude of both TB and tobacco exposure is

phenomenal, even a modest effect of the latter on the

former is likely to have substantial effect in terms of

absolute numbers and thus for epidemiological

purposes, TB control programs should start addressing

tobacco control as a potential preventive intervention.16

We did not find any significant difference in the

radiological findings between the two groups and this

observation is in variance with results from some of the

previous studies.10,13 However, it is not unusual for the

elderly and the young to have significant differences in

symptomatology and yet have similar radiological

presentation of PTB since the two aspects of the disease

do not necessarily correlate linearly.17, 20 Therefore, it is

not surprising that both elderly and young patients with PTB can manifest characteristic radiological findings (infiltrates with or without cavitation in the apicoposterior segments of one or both upper lobes or

in the apical segment of the lower lobes) as well as less typical findings (atelectasis basal infiltrations, nodules, miliary pattern or diffuse infiltrates).20 Moreover, we also did not find any difference between the two groups

in terms of past history of TB, physical findings or sputum AFB positivity rate Similarly, differences in the median values of ESR and TLC between the two groups, although statistically significant, may not be clinically relevant We feel that the differences in the manifestations of TB between the elderly and young patient groups were predominantly with respect to symptomatology This feature may be the result of epidemiological differences reflecting the prevalence and infection rates of tuberculosis It also has to been emphasised that considering TB as a diagnostic possibility is the most important and crucial step for preventing a diagnostic delay while evaluating elderly patients Infact, TB is often not even considered in the differential diagnosis by treating physicians and an incorrect initial diagnosis of TB is associated with the potential risk of delay in the institution of ATT and there

by facilitates silent spread of the disease.1 The current study had certain limitations First, the number of patients enrolled was relatively small Secondly, no distinction was made between out-patients and in-patients since the authors had felt that it would have been difficult to bring out any meaningful conclusions for out patients and in-patients separately

in view of the small numbers involved Moreover, the study was not primarily aimed at detecting a difference between out-patients and in-patients; rather it was an attempt to detect differences between the young and the elderly irrespective of their admission status For the same reason all patients admitted with active PTB were included and this was true whether they were admitted for problems related to the disease under study (PTB) or for other illnesses and had PTB as a co-morbidity Future prospective studies should, however, attempt to compare the characteristics and detect differences, if any, between out-patient and in-patient subgroups also Thirdly, since the enrollment was by means of

enrollment of fixed number (n = 50) of consecutive

patients with PTB in each group rather than by consecutive enrollment of all patients with PTB, the current study cannot provide data about the actual contribution of elderly patients to the overall burden of PTB in patients visiting healthcare facilities or in the community as a whole

ACKNOWLEDGEMENT

The authors wish to thank Dr A.N Aggarwal (Associate Professor, Department of Pulmonary Medicine, PGIMER, Chandigarh) for his help in the biostatistical analysis of the data.

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12th Congress

of the Asian Pacific Society of Respirology (APSR 2008)

OPTIMAL USE OF ADVANCED TECHNOLOGY

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19-22 November 2008

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