In many countries, including China, reported tuberculosis rates are twice as high in men as in women[7, 8]. Mediastinal tuberculous lymphadenitis, however, has been reported to be more common in females[9, 10], although the reasons are not well understood. Mediastinal lymphadenitis caused by tuberculosis and histoplasmosis are the most common etiologies of broncholithiasis. All patients in the present study had a history of tuberculosis with remaining infiltrates, as identified with interferon-γ release assays. As the position of lesions relative to the airway can be difficult to determine by chest CT, follow-up bronchoscopy should be performed to analyze calcification lesions detected near or in the airway. In addition, broncholiths of three patients in the present study were covered by granulomas. As granulomas may mimic bronchial carcinoma, a biopsy is often necessary to rule out neoplasm. Broncholithiasis is generally classiﬁed into three categories depending on whether the broncholiths are purely endobronchial, peribronchial, or mixed (transbronchial). This classiﬁcation is important, as it may have an impact on the therapeutic approach and potential complications.
For lithotripsy of the airway, neodymium-YAG (Nd:YAG) lasers generate too much heat, and may cause collateral damage to the surrounding normal tissue. As the absorption maximum of water (1940 nm) is close to the wavelength of the Ho:YAG laser, it can absorb much more Ho:YAG laser energy than that of a Nd:YAG laser (wavelength: 1064 nm). Furthermore, a Ho:YAG laser has a lower penetration depth (only 0.4 mm) in human tissues than does a Nd:YAG laser, which limits the risk of collateral damage. A Ho:YAG laser delivers short pulses of optical energy to the tip of the optical ﬁber, which causes instantaneous saline evaporation and creates a cavitation bubble; this is known as the “Moses effect.” This cavitation bubble oscillates and violently implodes, generating a shockwave that is transmitted to the target broncholith, causing its fragmentation. For maximum fragmentation, the optimal distance between the ﬁber tip and the broncholith is 1-2 mm[12, 13].
There are four main points that we want to highlight:
- Laser parameters: Choosing the appropriate parameters can increase the efficiency of lithotripsy and reduce the risk of complications. In vitro experiments have revealed that, for the same output power, low frequency-high pulse energy yields the highest efficiency of lithotripsy. We started our procedures with a pulse frequency of 5 Hz and a pulse energy 0.8 J. The highest pulse frequency we used was 15 Hz, and the highest pulse energy we used was 1.6 J. Within these parameters, we have demonstrated its safety and efficiency. We do not recommend using a high pulse frequency. However, if is clearly insufficient, the pulse energy may be appropriately increased.
- Lithotripsy technique: The energy from a Ho:YAG laser results in a cavitation bubble with a diameter of 2 mm. If the tip of the optical fiber is too close to the surface of the broncholith (<1 mm), it results in non-optimal cavitation bubble formation, causing a “drilling effect” rather than fragmentation. The distance between the tip of the optical fiber and the broncholith should be 1-2 mm for optimal fragmentation. If the distance is too large, the shock wave will attenuate before it reaches the broncholith.
- Strategy for different types of broncholiths: Chest CT scans with contrast should be reviewed carefully before lithotripsy, particularly for the position of the broncholith in the mediastinum (e.g., involvement of arteries or the esophagus), and the type of broncholith. (1) Endobronchial broncholiths can be fragmented via lithotripsy, and all fragments should be extracted, unless there is obvious artery involvement. (2) For transbronchial broncholiths, the endoluminal section is the focus, as excessive treatment of the peribronchial section may cause massive hemoptysis or fistula.
- Safety and complications: (1) The shell of an optic fiber is fragile and flammable, and its integrity should be verified before and during the procedure. (2) Lithotripsy should be performed under general anesthesia, in combination with rigid or flexible bronchoscopy, due to the risk of life-threatening hemoptysis. (3) During laser activation, the fraction of inspired oxygen should be lower than 40%, and jet ventilation should be halted. (4) The ﬁber should be held at a distance of at least 4 mm from the distal end of the scope, to protect the bronchoscope. (5) The bronchus must be filled with saline and the optical fiber should be close to or in contact with the broncholith. (6) Hemoptysis is one of the most common causes of fatality due to lithotripsy. Transbronchial broncholiths in the right intermediate bronchus and in the right main bronchus are more likely to result in massive hemoptysis or fistula. If life-threatening hemoptysis does occur, a bronchial blocker, a double-lumen endotracheal tube, bronchial artery embolization, or lobectomy should be implemented. (7) If a broncholith is located within a sinus fistula, the fistula will be exposed upon lithotripsy. We observed such BEF in two patients (patient 1 and 11) in our present study. (8) Following lithotripsy, obstructive pneumonia may result from mucosal edema and necrosis. We observed this phenomenon in two patients in the current study: they had postoperative fever, and pneumonia was confirmed via computed radiography or CT. The pneumonia may be improved with antibiotic treatment. (9) Overheating is a possibility during such procedures, and may damage the bronchoscope. Airway fire is another possible complication, the risk of which may be reduced by filling the bronchus with saline during laser activation, as we did in the current study. (10) Broncholithiasis may recur in the case of transbronchial broncholiths, due to broncholith movement over time. The intact section of the broncholith may protrude into the bronchial tree over the months following the procedure, and patients may require multiple procedures (e.g., in the case of patient 11). Loose broncholiths may also be expectorated after lithotripsy.
In summary, we demonstrated the safety and efficiency of Ho:YAG laser lithotripsy treatment of patients with broncholithiasis, when using a low pulse frequency and rigid or flexible bronchoscopy. Its energy is readily absorbed by water and its penetration is weak, reducing damage to normal tissue. Transbronchial Ho:YAG laser lithotripsy is a promising treatment for broncholithiasis; however, further research is required, preferably multicenter studies with larger sample sizes, in order to verify our findings.