INT J TUBERC LUNG DIS 19(7):808–810 Q 2015 The Union http://dx.doi.org/10.5588/ijtld.14.0983
Chronic airway obstruction after successful treatment of tuberculosis and its impact on quality of life I. Laniado de la Mora,*† D. Mart´ınez-Oceguera,*† R. Laniado-Labor´ın*†‡ ´ *Cl´ınica y Laboratorio de Tuberculosis, Hospital General Tijuana, Instituto de Servicios de Salud Publica, Tijuana, † ´ Facultad de Medicina y Psicolog´ıa, Universidad Autonoma de Baja California, Tijuana, Baja California, ‡Sistema Nacional de Investigadores, Consejo Nacional De Ciencia y Tecnolog´ıa, Mexico City, Mexico SUMMARY
Tuberculosis (TB) clinic in Tijuana, M´exico. Chronic airway obstruction (CAO) can be a sequella of pulmonary tuberculosis (PTB), independently of smoking history. O B J E C T I V E : To determine the prevalence of CAO in subjects recently recorded as cured after treatment of PTB, and its impact on quality of life. D E S I G N : Cross-sectional study. R E S U LT S : Overall, 34.3% of patients with a history of PTB had non-reversible CAO, defined as FEV1 ,70% post-bronchodilator. Subjects with CAO had significantly more radiographic fibrocavitary sequellae on chest X-rays, more extensive changes (1.8 6 0.8 affected quadrants vs. 1.3 6 0.6, P ¼ 0.04), more residual lung
cavities (1.4 6 0.8 vs. 0.5 6 0.7, P ¼ 0.002), and greater mediastinal retraction (42.4% vs. 16.7%, P ¼ 0.026). The mean COPD Assessment Test score for subjects with CAO was 15.1 6 10.4. The prevalence of irreversible CAO using the lower limit of normal criteria was higher (40%) than that calculated with fixed ratio criteria (34.3%). C O N C L U S I O N : Functional abnormalities are frequently already present at the end of treatment for PTB; patients with CAO are often symptomatic and experience a significant impact on quality of life. K E Y W O R D S : COPD; CAT questionnaire; spirometry; quality of life
IT HAS BEEN KNOWN FOR MORE THAN 50 years that chronic airway obstruction (CAO) can be a sequella of pulmonary tuberculosis (PTB) and that this association is independent of smoking history.1,2 In most reports, elderly patients have been diagnosed with chronic obstructive pulmonary disease (COPD) and the association with PTB was established retrospectively.3 However, empirical evidence suggests that airflow limitation can be present very early after completion of anti-tuberculosis treatment, depending on the degree of anatomical distortion present. Our objective was to determine both the prevalence of CAO in PTB subjects recently recorded as cured after anti-tuberculosis treatment, and its impact on quality of life, using a standardised questionnaire.
the highest TB rate among Mexican cities, at 50–60 cases per 100 000 population. All PTB patients recorded as cured in the last 3 years were invited to participate in the evaluation. The study protocol included a clinical history with detailed information on PTB and the COPD Assessment Test (CAT) questionnaire.4 The CAT is a very short (8 items), easy-to-complete health status questionnaire that helps patients and their clinicians assess the impact of COPD on quality of life.4 A score of 710 points indicates significant impact of CAO on quality of life.5 The protocol included chest X-ray (CXR), pulse oximetry (NCD Medicalw, Dublin, Ireland) and pre- and post-bronchodilator (inhaled salbutamol 300 lg) spirometry (Easy on-PCw, NDD Medical, Andover, MA, USA). We used the Global Initiative for Chronic Obstructive Lung Disease (GOLD)5 criteria for the diagnosis of COPD, i.e., the ratio of post-bronchodilator forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) of ,70%. Reference equations were those from the National Health and Nutrition Examination Survey III for Mexican
SETTING:
BACKGROUND:
STUDY POPULATION AND METHODS The Tuberculosis Clinic at the Tijuana General Hospital is a regional referral centre for ambulatory care for patients with drug-resistant TB and adverse drug reactions to anti-tuberculosis drugs. Tijuana has
Correspondence to: Rafael Laniado-Labor´ın, Cl´ınica y Laboratorio de Tuberculosis, Hospital General Tijuana, Instituto de Servicios de Salud Publica, Emiliano Zapata 1423, Zona Centro, Tijuana, Baja California, M´exico. Tel/Fax: (þ52) 664 686 ´ 5626. e-mail:
[email protected] Article submitted 24 December 2014. Final version accepted 7 February 2015.
TB and chronic airway obstruction
Table
809
Lung function results including pulse oximetry
Variable FVC PBD, l FEV1 PBD, l FEV1% PBD PBD change in FEV1, % FEV1% PBD (LLN) Pulse oximetry, %
Airway obstruction (n ¼ 24) mean 6 SD 2.44 1.32 57.3 6.7 73.1 97.4
6 6 6 6 6 6
0.9 0.6 9.95 4.9 2.2 1.9
No airway obstruction (n ¼ 46) mean 6 SD 2.50 2.02 80.9 8.6 75.9 96.6
6 6 6 6 6 6
0.7 0.5 7.4 10.2 3.9 2.1
% predicted mean 6 SD 62.1 6 16.6 58.4 6 15.6
P value 0.82 0.001 ,0.0001 0.41 0.002 0.11
SD ¼ standard deviation; PBD ¼ post-bronchodilator; FVC ¼ forced vital capacity; FEV1 ¼ forced expiratory volume in 1 s; LLN ¼ lower limit of normal.
Americans.6 The rate of CAO was also calculated by the lower limit of normal (LLN) criteria included in the spirometer software. Plethysmography was not available for the measurement of lung volume. Statistical analyses were performed using SPSSw, Version 19.0 (Statistical Package for the Social Sciences, IBM Corp, Armonk, NY, USA). The study protocol was approved by the ethics committee of the Hospital General Tijuana. Subjects provided signed informed consent to participate.
RESULTS Of the 70 patients included in the study, 24 (34.3%) had non-reversible CAO (defined as FEV1 ,70% post-bronchodilator; Table). Patients with CAO were older than those without (47.0 6 12.0 vs. 36.3 6 12.0 years, P , 0.001), and smoked more (7.46 6 7.8 vs. 2.4 6 5.3 pack-years, P ¼ 0.003). CAO was more frequent in males, although this difference did not reach statistical significance (42.2% vs. 20%, P ¼ 0.07). There was no difference in the frequency of CAO in subjects treated with first-line anti-tuberculosis drugs vs. those who also underwent treatment with second-line drugs (37.9% for CAO vs. 31.7, P ¼ 0.59). The TB episode was recent for both groups (2.7 6 4.3 years for those with CAO vs. 2.3 6 2.1 years for those without, P ¼ 0.75); the median time since completion of treatment for the CAO group was 2.1 years; 46.2% of those with CAO were evaluated at the time of discharge from PTB treatment. The mean number of TB episodes was significantly greater among subjects with CAO than among those without (1.9 6 0.7 vs. 1.4 6 0.6 episodes, P ¼ 0.009). Subjects with CAO had significantly more radiographic fibrocavitary sequellae on CXR, with more extensive changes (1.8 6 0.8 affected quadrants vs. 1.3 6 0.6, P ¼ 0.04), more residual lung cavities (1.4 6 0.8 vs. 0.5 6 0.7, P ¼ 0.002) and mediastinal retraction (42.4% vs. 16.7%, P ¼ 0.026) than those without AO. The mean CAT score for subjects with CAO was 15.1 6 10.4. The clinical threshold according to GOLD is 710 points. The mean CAT score for our patients was 15.1 6 10.4.
The prevalence of irreversible CAO using the LLN criteria was higher (40%) than that calculated with the fixed ratio criteria (34.3%).
DISCUSSION Our study shows that CAO was present at the time of completion of PTB treatment in almost half of patients with functional abnormalities. Unlike patients with smoking-related COPD, these patients were much younger (age ,50 years); however, PTB sequellae produce significant fixed CAO (FEV1 ,60% of predicted) and clinical impact on quality of life (the mean CAT score for our patients was .15 points). A recent literature review confirmed a positive association between TB and CAO, with odds ratios ranging between 1.37 and 2.94; this association is independent of smoking history.2 The literature reports that smoking becomes an important factor in the development of COPD in patients with a history of 710 pack years.7 Our patients with CAO smoked significantly more than those without CAO; however, the history of smoking among both groups was moderate and cannot alone explain the degree of obstruction observed. The effect of smoking and TB sequellae was undoubtedly additive in the development of CAO in this group of patients. Residual lung damage even after successful treatment of PTB includes fibrosis, bronchovascular distortion, emphysema and bronchiectasis. When extensive, it can lead to chronic respiratory insufficiency, cor pulmonale and premature death.2 The degree of functional impairment is likely to increase incrementally with repeated episodes of TB and the effect of age.3 The mean number of TB episodes in our patients was significantly greater in subjects with CAO than in those without. Radiographic sequellae of PTB are independently associated with CAO even after adjustment for age, sex and smoking history.8,9 Delays in diagnosis and treatment initiation of even a few weeks are likely to be associated with more extensive sequellae and more severe CAO.10 In our cohort, subjects with CAO had significantly more CXR sequellae than those without CAO.
810
The International Journal of Tuberculosis and Lung Disease
Although in the GOLD strategy5 PTB is one of the factors for the development of COPD, patients with CAO due to PTB are usually not treated according to COPD guidelines. Although there seems to be an increased risk of PTB relapse with chronic use of inhaled steroids,11 these patients could potentially benefit from treatment using only long-acting bronchodilators.
CONCLUSIONS Our responsibility towards patients with PTB does not end with the attainment of microbiological cure. Our study shows that functional abnormalities are frequently present at the time of discharge from antituberculosis treatment; patients with CAO are symptomatic and experience a significant impact on quality of life due to COPD, and virtually none of them are treated accordingly to established guidelines. Conflicts of interest: none declared.
References 1 Martin C J, Hallett W Y. The diffuse obstructive pulmonary syndrome in a tuberculosis sanatorium. II. Incidence and symptoms. Ann Intern Med 1961; 54: 1156–1164. 2 Allwood B W, Myer L, Bateman E D. A systematic review of the association between pulmonary tuberculosis and the development of chronic airflow obstruction in adults. Respiration 2013; 86: 76–85.
3 Hnizdo E, Singh T, Churchyard G. Chronic pulmonary function impairment caused by initial and recurrent pulmonary tuberculosis following treatment. Thorax 2000; 55: 32–38. 4 Jones P W, Harding G, Berry P, Wiklund I, Chen W H, Kline Leidy N. Development and first validation of the COPD Assessment Test. Eur Respir J 2009; 34: 648–654. 5 Global Initiative for Chronic Obstructive Lung Disease. The global strategy for the diagnosis, management and prevention of chronic obstructive lung disease. Updated 2015. Chapter 2: Diagnosis and assessment. Bethesda, MD, USA: GOLD, 2015. http://www.goldcopd.org/uploads/users/files/GOLD_Report_ 2015_Feb18.pdf Accessed March 2015. 6 Torre-Bouscoulet L, P´erez-Padilla R ; Grupo de Trabajo del Studio PLATINO en M´exico. Adjustment of several spirometric reference equations to a population-based sample in Mexico. Salud Publica Mex 2006; 48: 466–473. 7 Forey B A, Thornton A J, Lee P N. Systematic review with metaanalysis of the epidemiological evidence relating smoking to COPD, chronic bronchitis and emphysema. BMC Pulm Med 2011; 11: 36. 8 Lee S W, Kim Y S, Kim D S, Oh Y M, Lee S D. The risk of obstructive lung disease by previous pulmonary tuberculosis in a country with intermediate burden of tuberculosis. J Korean Med Sci 2011; 26: 268–273. 9 Hwang Y I, Kim J H, Lee C Y, et al. The association between airflow obstruction and radiologic change by tuberculosis. J Thorac Dis 2014; 6: 471–476. 10 Lee C H, Lee M C, Lin H H, et al. Pulmonary tuberculosis and delay in anti-tuberculous treatment are important risk factors for chronic obstructive pulmonary disease. PLOS ONE 2012; 7: e37978. 11 Brassard P, Suissa S, Kezouh A, Ernst P. Inhaled corticosteroids and risk of tuberculosis in patients with respiratory diseases. Am J Respir Crit Care Med 2011; 183: 675–678.
TB and chronic airway obstruction
i
RESUME CONTEXTE :
Dispensaire antituberculeux a` Tijuana,
Mexique. C A D R E : Une obstruction chronique des voies a´eriennes (CAO) peut eˆ tre une se´ quelle de la tuberculose pulmonaire (TBP) ; cette association est ind´ependante de la consommation de tabac. O B J E C T I F : D´eterminer la pr´evalence d’une CAO chez des personnes consid´er´ees comme gu´eries apr`es un traitement de TBP et e´ valuer l’impact de la CAO sur la qualit´e de vie. S C H E´ M A : Etude transversale. R E´ S U LT A T S : Un total de 34,3% des patients ayant des ant´ec´edents de TBP avaient une CAO d´efinie par un volume expiratoire maximum seconde (VEMS) ,70% apre` s administration de bronchodilatateurs. Les personnes pr e´ sentant une CAO avaient
significativement plus de s´equelles radiographiques fibrocavitaires a` la radiographie pulmonaire, des modifications plus e´ tendues (1,81 6 0,8 quadrants affect´es contre 1,3 6 0,6 ; P ¼ 0,04), davantage de cavit´es pulmonaires r´esiduelles (1,41 6 0,8 contre 0,48 6 0,7 ; P ¼ 0,002) et de r´etraction m´ediastinale (42,4% contre 16,7% ; P ¼ 0,026). Le score CAT moyen des personnes souffrant d’une CAO e´ tait de 15,1 6 10,4. La pr´evalence d’une obstruction irr´eversible des voies a´eriennes d´efinie par la limite inf´erieure des crit`eres normaux e´ tait plus e´ lev´ee (40%) que celle calcul´ee avec les crit`eres fixes (34,3%). C O N C L U S I O N S : Les anomalies fonctionnelles sont fr´equemment d´eja` pr´esentes apr`es traitement de TBP ; les patients atteints de CAO sont symptomatiques et souffrent d’un impact significatif sur leur qualit´e de vie. RESUMEN
Cl´ınica de tuberculosis (TB) en Tijuana, M´exico. La obstruccion ´ cronica ´ de la v´ıa a´erea (CAO) puede ser una secuela de la tuberculosis pulmonar (TBP); esta asociacion ´ es independiente de la historia de tabaquismo. O B J E T I V O: Determinar la prevalencia de CAO en pacientes recientemente curados de TBP, y el impacto de esta CAO sobre la calidad de vida. ˜ D I S E NO: Estudio de corte seccional. R E S U L T A D O S: Presentaban con CAO no reversible 34,3% de los pacientes (FEV 1 ,70% post broncodilatador). Los sujetos con CAO presentaban en las radiograf´ıas tora´cicas una mayor frecuencia de secuelas fibrocavitarias, lesiones ma´s extensas (1,81 6 S E D E:
M A R C O D E R E F E R E N C I A:
0.8 cuadrantes afectados vs. 1,3 6 0,6; P ¼ 0,04), mayor numero ´ de cavitaciones residuales (1,41 6 0,8 vs. 0,48 6 0,7; P ¼ 0,002) y retraccion ´ mediastinal (42,4% vs. 16,7%; P ¼ 0,026). El puntaje en el cuestionario respiratorio COPD Assessment Test en los sujetos con CAO fue de 15,1 6 10,4. La prevalencia de CAO utilizando el para´metro del l´ımite inferior del normal fue mayor (40%) que el calculado con el criterio de la relacion ´ fija (34,3%). C O N C L U S I O N: Las anomal´ıas funcionales se encuentran ya frecuentemente al momento del tratamiento exitoso de la TBP; la CAO ejerce un impacto negativo muy significativo sobre la calidad de vida.
