In this study, we analysed the clinical course of 421 patients with NTM-PD according to the size of cavities at the time of diagnosis. We found that patients with cavities > 2 cm had worse treatment outcomes than did patients with non-cavitary NTM-PD. In contrast, patients with cavities ≤ 2 cm had treatment outcomes that were comparable to those of patients with non-cavitary NTM-PD. Our results support the need for planning treatment according to the radiographic features of cavities in patients with NTM-PD.
The presence of cavities in patients with NTM-PD has been recognised as an indicator of poor prognosis . Cavities are associated with unfavourable treatment outcomes, including higher mortality [20, 21]. Cavity formation has been found more commonly in patients who do not respond to treatment than in those with culture conversion . Additionally, the presence of a cavity increases the risk of all-cause mortality in patients with Mycobacterium avium complex pulmonary disease (MAC-PD) . Moreover, large cavities are strongly associated with disease progression . However, the impact of detailed differentiation based on radiographic findings has not been reported.
NTM-PD has been classified into NB and FC types . However, it is sometimes difficult to clearly differentiate between these types. Bronchiectasis co-exists with cavities in most patients with NTM-PD . Pathologic findings on examination of specimens from patients with NTM-PD has suggested that peri-bronchial nodules evolve into cavities . Another cohort study found that cavities develop over time, even in the NB form of MAC-PD . If we assume that bronchiectasis and cavities are on the same disease spectrum, NTM-PD could be differentiated initially by the presence of one or more cavities and the extent of those cavities. In our study, we classified NTM-PD according to the presence and size of cavities.
Patients with cavitary NTM-PD more frequently received antibiotic treatment than those without cavities. When the cavity was > 2 cm in diameter, the treatment outcome was unfavourable. The mortality rate was also higher in patients with cavities > 2 cm. However, the cavities ≤ 2 cm did not affect the clinical outcomes. In our study, cavities only had an impact on the prognosis of patients with NTM-PD when they were > 2 cm.
Cavitation in the lung results from a number of pathological processes, including suppurative, caseous, and ischemic necrosis . In NTM-PD, cavitation occurs in patients with more extensive disease and the cavities contain numerous organisms [24, 25]. Drugs penetrate cavities poorly and sub-therapeutic drug concentrations in these lesions can lead to acquired drug resistance . These factors explain the worse outcomes of patients with NTM-PD with cavities > 2 cm.
Interestingly, in our study, a small cavity (< 2 cm) was not associated with poor prognosis. Large cavities were more prevalent in progressive cavitary NTM-PD . Thus, the favourable outcomes of small cavities in patients with NTM-PD may be attributable to slow disease progression. Another possible explanation is that, once such cavities have been detected, more careful monitoring and aggressive treatment are adopted, resulting in favourable outcomes given that such patients respond better to treatment than do those with larger cavities.
Our findings suggest the need for more detailed planning of treatment for cavitary NTM-PD according to the characteristics of the cavities. Recent guidelines recommend initiation of antibiotic treatment for NTM-PD rather than watchful waiting, especially when sputum smears are positive for acid-fast bacilli or when there is evidence of cavitary lung disease . Parenteral agents are recommended for cavitary disease in patients with MAC-PD, [2, 10]. Our results suggest a more complex treatment strategy for patients with cavitary NTM-PD. In patients with > 2 cm, immediate and intensive treatment is indicated. If the cavity size is ≤ 2 cm, whether or not to treat should be decided on the basis of the overall clinical situation, under the premise that watchful follow-up is guaranteed.
Retrospective studies from South Korea have shown that the condition of about 40% of patients with non-cavitary NB NTM-PD remains stable when they are observed without treatment [27, 28]. Spontaneous culture conversion occurs in 35–50% of untreated patients [27, 28]. In our study, spontaneous conversion was achieved in 12 of 28 patients (42.9%) with cavitary NTM-PD who had been undergoing regular monitoring without initiation of treatment. Thus, when an immediate initiation of treatment is not available, watchful waiting might be a valid management option for patients with small cavities, once close monitoring is ensured.
This study has some limitations. First, the causes of the cavities could not be determined. Although the cavities were suggested to be the manifestation of NTM-PD, we could not completely exclude the possibility of combined fungal infection or other chronic infection [29, 30]. Second, we did not use the classical classification of NB or FC forms in our analysis. In fact, cavities frequently co-exist with bronchiectasis and some of cavities develop from bronchiectatic changes . It is difficult to distinguish between non-cavitary NB, cavitary NB, and FC types in some patients. In contrast, a classification based on size may be easier to use.