We evaluated the impact of emphysema on AFB sputum TCC rates following initiation of anti-TB treatment in hospitalized PTB patients at Jikei University Daisan Hospital. Median TCC was significantly delayed in 38 PTB patients (52.0 days) with emphysema compared with 41 patients without emphysema (28.0 days). Multivariate Cox proportional hazards analysis showed that emphysema, cavities, and baseline TTD within 2 weeks were associated with delayed TCC. With regard to PTB-related CT findings, cavities and consolidation were seen more frequently in PTB patients with than without emphysema (71.05% vs 43.90%; p=0.015, and 84.21% vs 60.98%; p=0.021, respectively).
To our knowledge, this is the first study to report the impact of emphysema on sputum culture conversion in PTB patients. We focused on emphysema detection using CT. Emphysema was defined using the current standard of LAA<-950 [11, 14]. Although no well-validated biomarker of COPD has been identified other than forced expiratory volume in 1 second (FEV1), various quantitative imaging methods for emphysema are being developed to reveal the relationship between emphysema and COPD phenotype, including airflow limitation and level of matrix metalloproteinases (MMPs) [11–14]. CT is a minimally invasive technique that can identify the pathological features of emphysema. Goddard score based on the LAA proportion is widely used to measure emphysema [22, 24, 25]. Average Goddard score of emphysema patients was 6.74±4.73 in our study. The severity of most emphysema cases was categorised as mild or moderate according to previous reports . Our data suggest that even a mild level of emphysema has a negative influence on the duration of PTB treatment required for sputum culture conversion. Multivariate Cox proportional hazards analysis showed that emphysema was more significantly associated with delayed MTB culture conversion than smoking history was (not significant). According to recent reports, smoking history (current or former) has a negative impact on PTB clinical outcome, including delayed culture conversion [6, 27]. Although smoking history based on medical interview is a simple method to assess smoking exposure, the relationship between amount of smoking and smoking-associated immune response remains unclear. The reversibility of immune modification by smoking cessation is still unknown. Our results suggest that emphysema detection using CT is useful for predicting the duration of TB treatment required for sputum culture negative conversion.
The host immune response is crucial in TB pathogenesis, as demonstrated by the increase in incidence and mortality in immunocompromised hosts . AMs are involved in the host inflammatory defence against MTB . MTB is transmitted through air droplets and is an intracellular bacterium that infects AMs and dendritic cells (DCs) localized to the alveoli. The innate immune response is activated and inflammatory cells are recruited to the lungs. MTB that can evade the host immune system within AMs and DCs drives granulomatous inflammation and establishes PTB.
Recent reports suggest that smoking habit increases the risk of developing active TB and mortality [27, 29], and smoking-modulated immune dysfunction might be involved in TB pathogenesis [6, 27]. Although the pathogenesis of COPD/emphysema is not fully understood, it is associated with smoking-induced chronic inflammation of airways and lung parenchyma. After amplification of inflammation in patients with COPD, abnormal inflammatory immune responses are sustained even after smoking cessation . AMs also play a central role in chronic inflammation in COPD . AMs are activated by cigarette smoke extract, and secrete inflammatory mediators, including tumour necrosis factor-α, chemokine C-X-C motif ligand (CXCL)1 and CXCL8. AMs release elastic enzymes (MMPs) that contribute to emphysematous changes . Macrophages are localized to sites of alveolar wall destruction in patients with emphysema, and there is a correlation between number of AMs and severity of emphysema . AMs from patients with COPD show reduced phagocytic uptake of bacteria, which might be a factor in bacterial colonization [10, 29]. These reports suggest that smoking-associated immune modification in emphysema is involved in delayed TCC in terms of increased PTB severity and reduced response to anti-TB therapy.
Patients’ immune function also affects the radiological findings of PTB . PTB-related CT findings differ between patients with or without emphysema. Jeon et al. reported that PTB patients with emphysema often show pneumonia-like consolidation, suggesting that impaired innate immunity in emphysema causes PTB progression and expansion of inflammation . In our study, cavities and consolidation were seen more frequently in PTB patients with emphysema than in those without emphysema (71.05% vs 43.90%; p=0.015, and 84.21% vs 60.98%; p=0.021, respectively) (Table 2). Cavity lesions are associated with the greatest bacterial load, suggesting highly infectious and severe PTB [33, 34]. It is speculated that smoking-related immune modification in emphysema contributes to more severe radiological findings and extension of TCC.
This study had some limitations. First, this was a small, single-center retrospective study. Nevertheless, our finding of a negative effect of emphysema on sputum TCC suggests that emphysema is a potential risk factor for PTB development in terms of smoking-related immune dysfunction. In future, a larger prospective study could reveal the relationship between CT-detected emphysema and clinical outcome of PTB. Second, we needed to enroll patients with confirmed COPD with emphysema to determine the relationship between COPD/emphysema and sputum culture conversion. To diagnose COPD, airflow limitation must be identified with spirometry. However, it is impossible to estimate accurately airflow limitation in patients with COPD and active PTB at baseline.
Third, we could not analyze female patients because there were only three women with PTB with emphysema. From the 1970s to 1990s, smoking rate for Japanese women was only 10%–15%, while that for men was 55%–80% . Although the difference became smaller after the 2000s, the risk of emphysema in Japanese women is potentially lower than in men.
In conclusion, CT-detected emphysema with a Goddard score ≥1 is associated with delayed AFB sputum culture conversion and PTB-related CT findings. If confirmed in larger populations of PTB patients with emphysema, CT-detected emphysema could be helpful for predicting the duration of PTB treatment required for sputum culture negative conversion.