|Year : 2022 | Volume
| Issue : 2 | Page : 97-101
New onset adult asthma attributable to tuberculosis: A distinct phenotype?
Kundan Mehta, Kiran A Balani, Tushar R Sahasrabudhe
Department of Respiratory Medicine, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra, India
|Date of Submission||27-Apr-2022|
|Date of Acceptance||19-Jul-2022|
|Date of Web Publication||19-Dec-2022|
MD, DETRD, FCCP Tushar R Sahasrabudhe
Professor, Department of Respiratory Medicine, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune 411018, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: In clinical practice, we encounter cases of bronchial asthma the onset of which correlates with past tuberculosis (TB), either pulmonary or extrapulmonary. Our study attempts to validate this observation and assess likelihood of new asthma that is attributable to TB. Methods: It was a single visit, cross-sectional study of persons who had TB within last 5 years (group 1). Preexisting asthma before TB, COPD cases, smokers, and persons with any active infective or diffuse lung diseases were excluded. Their spouse (group 2) and first-degree relatives (group 3) served as controls. All participants were subjected to detailed history, examination, and spirometry. Sample size was 225 (75 in each group). Results: About 62/75 participants in group 1 had intermittent or persistent symptoms suggesting obstructive airway disease that started within a year of TB diagnosis. Obstructive spirometry pattern was observed in 23/75 (30.6%) post-TB cases, compared to 6/75 (8%) in group 2 and 4/75 (5.33%) in group 3 participants. While, 11/75 (14.66%) post-TB cases in comparison to 7/150 (4.66%) controls were diagnosed as asthma after clinical correlation. About 24% of persons with post-TB lung scarring, 16% without lung scarring, and 4% with only extrapulmonary TB were diagnosed as asthma. Attributable risk for post-TB asthma was significant (0.1). Conclusion: This study suggests causative association between TB and asthma rather than just comorbidity. Further large-scale studies are warranted.
Keywords: Asthma, obstructive airway disease, TB
|How to cite this article:|
Mehta K, Balani KA, Sahasrabudhe TR. New onset adult asthma attributable to tuberculosis: A distinct phenotype?. J Assoc Chest Physicians 2022;10:97-101
|How to cite this URL:|
Mehta K, Balani KA, Sahasrabudhe TR. New onset adult asthma attributable to tuberculosis: A distinct phenotype?. J Assoc Chest Physicians [serial online] 2022 [cited 2023 Jan 27];10:97-101. Available from: https://www.jacpjournal.org/text.asp?2022/10/2/97/364438
| Introduction|| |
Obstructive airway diseases (OADs) on spirometry have been broadly classified into reversible, irreversible, or partly reversible and predominantly small airway disease. Asthma and its phenotypes have been extensively studied and it is generally believed that respiratory infections act as a trigger rather than the cause of asthma, the only exception being childhood respiratory infections. Pulmonary tuberculosis (TB) may lead to airway obstruction by a wide variety of mechanisms such as airway mucosal damage causing bronchial hyperreactivity, allergy to tuberculoprotein, mucus plugging, etc., to mention a few. Common sequelae of pulmonary TB such as lung fibrosis, cavitation, resorptive collapse, bronchiectasis, bronchial stenosis, etc., also cause airway obstruction in addition to the restrictive dysfunction., TB has also now been recognized by global initiative for chronic obstructive lung disease (GOLD) guidelines as an important risk factor of COPD.
We in clinical practice noted that many patients with typical symptoms of asthma and its spirometry confirmation, give history of TB in the past and in many, the onset of asthmatic symptoms strikingly correlates with the occurrence of TB. This correlation was observed in patients who had pulmonary TB with or without radiological evidence of lung damage. Interestingly, it was also observed in patients who had extrapulmonary TB. The present study was, therefore, planned to investigate into and validate this clinical observation. Similar observations have also been made by others in the past. Global Initiative for Asthma (GINA) has, however, not yet recognized TB as a potential cause of asthma due to lack of enough evidence., Validating our clinical observation was therefore important. This is more prudent for India as both TB and asthma are highly prevalent in the country. On MEDLINE search, we found that only a few studies are available which point toward existence of post-TB asthma as an entity.
| Methods|| |
This was a single visit, cross-sectional, observational study. Permission was obtained from the institutional ethics committee before the commencement of the study.
Patients with documented evidence of pulmonary or extrapulmonary TB and its treatment within past 5 years were screened as potential study participants. Informed consent, age between 18 and 80 years, ability to perform spirometry, and willingness for study procedures were the inclusion criteria. Persons with active TB, those who had taken irregular treatment for TB, those with onset of OAD before TB, lung damage due to any reason other than TB, any other active infective or diffuse lung disease that could affect spirometry, and those with history of tobacco smoking were excluded from the study. These patients comprised the study group 1.
A second group, group 2, included first-degree blood relative of study participants in group 1 (thus sharing genetic predisposition to asthma), and third group (group 3) included spouse of group 1 participants, sharing same environment for at least 1 year (for unmarried participants, a person haring same environment for >1 year was included). Persons with past or active TB, lung damage due to any reason, any active infective or diffuse lung disease that could affect spirometry, and those with history of tobacco smoking were excluded from group 2 and group 3.
Total 75 subjects were enrolled in each group. The study group (group 1) was further subdivided into three subgroups (A, B, and C) for analytical purpose. Subgroup A were persons who had pulmonary TB resulting in structural lung damage as determined by X-ray, subgroup B were without obvious lung damage (normal chest X-ray), and subgroup C were persons who had only extrapulmonary TB and normal chest radiograph at the time of enrolment.
All the three corresponding participants (subject in group 1 with his relative in group 2 and spouse in group 3) were assessed simultaneously within a window of ±7 days. Informed consent was obtained from each study participant before carrying out any study-related procedures. Any symptomatic and spirometry evidence of OAD was sought. All details of past TB and its treatment were captured. Chest radiograph was obtained to assess the extent of scarring. Any active lung disease was ruled out by carrying out relevant investigations including sputum for ZN stain. Spirometry with postbronchodilator reversibility testing was performed for every study participant. For those already diagnosed as OAD, a window period of 4 weeks from prior exacerbation or last systemic steroid use was maintained. Bronchodilators were withdrawn for at least 24 hours before performing spirometry.
| Observation and Results|| |
About 62/75 patients in group 1 had intermittent/persistent symptoms of OAD that started within 1 year of TB diagnosis. The numbers were 13/75 and 3/75 for group 2 and group 3, respectively [Table 1]. Correlating spirometry evidence of OAD was looked at. In group 1, 30.6% (23/75) had spirometry evidence of OAD, out of which 12 (16%) had irreversible obstruction and 11 (14.66%) had reversible obstruction favoring asthma (>12% and 200 mL improvement in FEV1), as per GINA criteria.
Prevalence of correlating OAD in group 2 (first-degree relatives sharing common genetic factor) was 6/75 (8%). About 2/75 (2.66%) had irreversible obstruction and 4/75 (5.33%) had reversible obstruction favoring asthma.
Prevalence of correlating OAD in group 3 (spouse/relative sharing same environmental factor) was 4/75(5.33%), out of which one (1.33%) had irreversible obstruction and three (4%) had reversible obstruction favoring asthma.
The data was analysed using IBM SPSS statistical software version 21.0, NY, USA. The findings as summarized in [Figure 1] were statistically significant (p-value < 0.001).
Subgroup analysis [Table 2] clearly showed that the prevalence of OAD in patients with extrapulmonary TB too was higher than the control groups (groups 2 and 3) with P-value < 0.001. This suggests that some mechanisms other than direct lung injury are at play, causing development of post-TB OAD. About 24% of persons with post-TB lung scarring, 16% without lung scarring, and 4% with only extrapulmonary TB were diagnosed as asthma after clinical correlation.
The risk of post-TB OAD was calculated as per the formula quoted in
Attributable risk (AR) = Ie - Iu where,
Incidence in exposed (le) = number of exposed people who get the disease/total number of exposed people.
Incidence in unexposed (Iu) = number of unexposed people who get the disease/total number of unexposed people.
Attributable risk for post-TB OAD was 0.24 (Ie = 23/75, Iu = 10/150) and that for post-TB asthma was 0.1 (Ie = 11/75, Iu = 7/150). Attributable risk of asthma on adjusting for variable of genetic predisposition was 0.093 (Ie = 11/75, Iu = 4/75) and on adjusting for variable of environmental predisposition was 0.106 (Ie = 11/75, Iu =3/75).
It was strikingly evident from the analysis that the prevalence of asthma is significantly higher in post-TB cases. This seems to be a distinct phenotype which follows pulmonary or extrapulmonary TB, even after partly adjusting for genetic and environmental variables.
| Discussion|| |
TB, a disease of great antiquity is still one of the top communicable diseases in the world. Worldwide, TB is the 13th leading cause of death and the second leading infectious killer after COVID-19. Most national TB programs, however, focus only on cure or treatment completion and do not adequately address the sequelae of TB which may result in persistent morbidity.
Bronchial asthma and COPD are common respiratory illnesses in the world and in India. The estimated current prevalence globally for bronchial asthma (doctor-diagnosed) is 4.3%. They cause a great deal of morbidity. Though TB has been recognised as a risk factor for COPD, bronchial asthma is not.
Tuberculosis and bronchial asthma do not reach peak of its activity at the same time due to different immunological mechanisms. The Th1 and Th2 subgroups of lymphocytes regulate development of tuberculosis and bronchial asthma, respectively. Studies support this hypothesis by demonstrating an increased proportion of Th2 lymphocytes in peripheral blood and airway of asthmatic patients. After antitubercular treatment, the enhanced levels of Th1 come down and a proportion of patients develop Th2 mediated airway obstruction which on aggravation may emerge as bronchial asthma.
Studies of family history, twins, familial aggregation, and segregation studies in asthma have convincingly shown that the disease has a strong genetic component. It is likely that the risk of developing asthma is greatest when both genetic and environmental risk factors are present together. The inheritance of asthma and allergy does not follow the classical Mendelian patterns of inheritance., Spain and Cooke reported that the overall prevalence of asthma in the first-degree relatives of asthmatics was 58.4%. We interpreted our findings by partly adjusting for these variables.The average duration of onset of OAD after TB is variable. Study undertaken by Hnizdo et al. found that the loss of lung function was highest within 6 months of diagnosis of TB and stabilized after 12 months when the loss was considered as chronic.
There are two limitations to our study. Firstly, as ours was more of a “proof of concept” study, the sample size was small and hence, there is a need for larger studies. Secondly, as the etiopathogenesis is more complex with various prevalent phenotypes and genotypes, an attempt was made to match the control group for limited number of variables, although the important ones. Genetic factors (Th1 and Th2 typing was not done) and environmental factors (working environment for spouse is different, though they share the same home environment for maximum time) are therefore only partly matched.
Mechanism by which pulmonary TB causes asthma is still not clear, especially in extrapulmonary TB, which needs further research.
Whether this phenotype behaves differently in terms of frequency of exacerbations, response to medication, etc., needs to be studied with longitudinal studies over a longer period of time.
| Conclusion|| |
Strong clinical observation of emergence of asthma cases after TB led us to conduct this study which confirms a strong correlation between TB and asthma, even after partly matching genetic and environmental variables. The attributable risk was statistically significant. Further research would certainly clarify the picture.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kuruvilla ME, Lee F, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol 2019;56:219-33.
Ahanchian H, Jones CM, Chen YS, Sly PD. Respiratory viral infections in children with asthma: do they matter and can we prevent them? BMC Pediatr 2012;12:147.
Garcia-Garcia ML, Rey CC, del Rosal Rabes T. Pediatric asthma and viral infection. Arch Bronconeumol 2016;52:269-73.
Kim HY, Song KS, Goo JM, Lee JS, Lee KS, Lim TH. Thoracic sequelae and complications of tuberculosis. Radiographics 2001;21:839-60.
Dheda K, Booth H, Huggett JF, Johnson MA, Zumla A, Rook GA. Lung remodeling in pulmonary tuberculosis. J Infect Dis 2005;192:1201-10.
Rajasekaran S, Savithri S, Jeyaganesh D. Post-tuberculosis bronchial asthma. Indian J Tub 2001;48:139-42.
Quirt J, Hildebrand KJ, Mazza J, Noya F, Kim H. Asthma. Allergy Asthma Clin Immunol 2018;14(Suppl 2):50.
Toshniwal V, Singhal P, Macherla S. Asthma as a sequelae to pulmonary tuberculosis. Eur Respir J 2017;50:PA2719.
Byrne AL, Marais BJ, Mitnick CD, Lecca L, Marks GB. Tuberculosis and chronic respiratory disease: a systematic review. Int J Infect Dis 2015;32:138-46.
Basham CA, Karim ME, Cook VJ, Patrick DM, Johnston JC. Post-tuberculosis airway disease: a population-based cohort study of people immigrating to British Columbia, Canada, 1985–2015. EClinicalMedicine 2021;33:100752.
Bijanzadeh M, Mahesh PA, Ramachandra NB. An understanding of the genetic basis of asthma. Indian J Med Res 2011;134:149-61.
] [Full text]
Los H, Koppelman GH, Postma DS. The importance of genetic influences in asthma. Eur Respir J 1999;14:1210-27.
Ralph AP, Ardian M, Wiguna A et al.
A simple, valid, numerical score for grading chest x-ray severity in adult smear-positive pulmonary tuberculosis. Thorax 2010;65:863-9.
World Health Organization. Global tuberculosis report 2021. Geneva, Switzerland: World Health Organization 2021.
Asher MI, García-Marcos L, Pearce NE, Strachan DP. Trends in worldwide asthma prevalence. Eur Respir J 2020;56:202094.
Prete GD. Human Th1 and Th2 lymphocytes: their role in the pathophysiology of atopy. Allergy 1992;47:450-5.
Cookson WO. Asthma genetics. Chest 2002;121:7S-13S.
Spain WC, Cooke RA. Studies in specific hypersensitiveness: XI. The familial occurrence of hay fever and bronchial asthma. J Immunol 1924;9:521-69.
Hnizdo E, Singh T, Churchyard G. Chronic pulmonary function impairment caused by initial and recurrent pulmonary tuberculosis following treatment. Thorax 2000;55:32-8.
Ravimohan S, Kornfeld H, Weissman D, Bisson GP. Tuberculosis and lung damage: from epidemiology to pathophysiology. Eur Respir Rev 2018;27:170077.
[Table 1], [Table 2]