Exploring lung cavity access to endobronchial valve in chronic pulmonary aspergillosis and nontuberculosis mycobacterial diseases, a radiological feasibility study

Extract

Nontuberculous mycobacteria (NTM) and chronic pulmonary aspergillosis (CPA) are emerging noncommunicable cavitary infections often arising in compromised lungs, especially after tuberculosis infection [1, 2]. Their incidence is increasing in France and worldwide [1, 2]. Therapeutic options for these two infections are limited and potentially toxic. Their management is difficult, marked by frequent failures (mainly related to cavity) and frequent relapses [3–7]. Surgical resection of infected lung segments can be curative [8, 9] but is often not feasible due to patients’ health conditions. The 5-year mortality rate directly associated with their appearance remains unacceptable, estimated at just over 40% [1, 2, 7]. There is therefore a strong need for new therapeutic options.

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This study demonstrates the radiological feasibility of targeting cavities with endobronchial valves in patients with mycobacterial or aspergillosis chronic lung infection and provides essential data for protocol development. https://bit.ly/43STpPH

To the Editor:

Nontuberculous mycobacteria (NTM) and chronic pulmonary aspergillosis (CPA) are emerging noncommunicable cavitary infections often arising in compromised lungs, especially after tuberculosis infection [1, 2]. Their incidence is increasing in France and worldwide [1, 2]. Therapeutic options for these two infections are limited and potentially toxic. Their management is difficult, marked by frequent failures (mainly related to cavity) and frequent relapses [3–7]. Surgical resection of infected lung segments can be curative [8, 9] but is often not feasible due to patients’ health conditions. The 5-year mortality rate directly associated with their appearance remains unacceptable, estimated at just over 40% [1, 2, 7]. There is therefore a strong need for new therapeutic options.

Endobronchial valves (EBVs) are now approved for management of severe emphysema and bronchopleural fistulas [10]. Unidirectional and reversible, this device is designed to prevent the inflow of inhaled air reaching the segment or target lobe, while allowing the outflow of air and secretions during exhalation. Reducing the oxygenation of the treated segments, they could represent an option for the treatment of microorganisms (including NTM and Aspergillus) whose growth is closely linked to the presence of oxygen. They have thus been evaluated as adjuvant treatment of multidrug-resistant tuberculosis (MDR-TB) [11–13]. In a randomised trial by Levin et al. [12], the placement of EBVs in 49 MDR-TB patients in treatment failure for ≥1 year, resulted in a 67% closure rate at 6 months, compared to 21% without EBVs. Additionally, patients receiving EBVs had higher culture conversion rates. More recently, An et al. [13] reported a closure rate of 69% and a culture conversion rate of 100% in 35 patients with MDR-TB following EBV placement.

Although these results seem encouraging, this strategy has not been evaluated in the treatment of NTM and CPA, and the number of patients eligible for this collapse therapy remains unclear. The objective of this preliminary study was to evaluate the eligibility of local EBV treatment in a real-life population with chronic cavitary lung infection based on a review of their radiological patterns, i.e. number of target cavities, and number and diameters of drainage bronchi.

We retrospectively included 21 patients followed in the Respiratory Medicine Department of Tenon Hospital (Paris, France) and having at least one scheduled computed tomography (CT) scan between 1 January 2023 and 1 June 2023 for NTM and/or CPA follow-up. Demographic, clinical and radiological characteristics were extracted from medical records. The most recent chest CT was assessed by a thoracic interventional radiologist to identify target cavities, their characteristics and eligible drainage bronchi for EBV placement. We particularly considered cavity size >2 cm because this is the limit of size impacting the NTM prognosis [14], and usually used to assess cavitary lesions in CPA [15].

Additionally, interventional bronchoscopists conducted an independent review using the superDimension Navigation System with LungGPS Technology Version 7.1 to evaluate the drainage bronchi. No assessment of segmental or lobar collateral ventilation was performed.

The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Institutional Review Board of the French learned society for respiratory medicine (Société de Pneumologie de Langue Française) (CEPRO number 2023-035).

A total of 21 patients were retrospectively included (table 1). Among them, 10 (47.6%) had CPA monoinfection, four (19.0%) had NTM monoinfection and seven (33.3%) had NTM and CPA co-infection. Patients’ characteristics, including respiratory and general comorbidities, were consistent with those typically observed in NTM and CPA populations [1, 2]. The proportion of patients receiving specific anti-infective treatment was 100.0% in NTM monoinfected patients, 90.0% in CPA monoinfected patients and 28.6% in coinfected patients. Nine (42.9%) patients had history of haemoptysis. The median (interquartile range) number of target cavities (>2 cm) was 1 (1–1). Five (23.8%) patients were not eligible for EBV placement because they did not have a target cavity. In the other 16 patients (including 13 with a unique cavity), the main target cavity locations were the left apex (nine cavities, 45.0%) and right upper lobe (eight cavities, 40.0%). The median highest diameter was 55 (29.5–67.2) mm. The wall median thickening was 7.1 (4.6–9.5) mm. Mycetoma was observed in seven cavities (35.0% of CPA patients). For others, cavitary lung infection was suggested by their wall thickenings. Among the 16 patients with at least one target cavity, the median number of drainage bronchi was 1 (1–2). Only one (6.3%) patient with a target cavity had an EBV use exclusion criterion, i.e. the absence of an individualised drainage bronchus. The additional examination performed by a bronchoscopist, using the superDimension Navigation System with LungGPS Technology Version 7.1, did not identify any additional drainage bronchi.

TABLE 1.

Characteristics and accessibility to target pulmonary cavities in the 21 included patients

Patients’ characteristics	Age, years	60 (44–66)
	Smoking history	10 (47.6)
	Haemoptysis	9 (42.9)
	BMI, kg·m−2	18.7 (17–23)
	Underlying respiratory diseases
	Thoracic surgery history	4 (19.0)
	Thoracic radiation history	1 (4.8)
	Emphysema	7 (33.3)
	Tuberculosis cavity history	9 (42.9)
	Bronchiectasis	10 (47.6)
	Lung fibrosis	1 (4.8)
NTM or cavitary aspergillosis cavitary infection	CPA monoinfection	10 (47.6)
	Receiving treatment n (% of CPA monoinfection)	9 (90.0)
	NTM lung disease monoinfection	4 (19.0)
	Receiving treatment n (% of NTM monoinfection)	4 (100.0)
	CPA/NTM coinfection	7 (33.3)
	Receiving treatment n (% of CPA/NTM coinfection)	2 (28.6)
Target cavity >2 cm	n=0	5 (23.8)
	n=1	13 (61.9)
	n=2	2 (9.5)
	n=3	1 (4.8)
Target cavity location #	Right upper lobe	8 (40.0)
	Middle lobe	0
	Right lower lobe	0
	Left apex	9 (45.0)
	Lingula	1 (5.0)
	Left lower lobe	2 (10.0)
Target cavity characteristics #	Highest diameter, mm	55 (29.5–67.2)
	Wall thickening, mm	7.1 (4.6–9.5)
	Fungal ball, n (% of CPA)	7 (35.0)
Drainage bronchus ¶	n=0	1 (6.3)
	n=1	9 (56.3)
	n=2	2 (12.5)
	n=3	1 (6.3)
	n=4	1 (6.3)
	n=5	1 (6.3)
	n>5	1 (6.3)
	Diameter of drainage bronchus in, mm	6.5 (5.8–7.1)

Data are presented as median (interquartile range) or n (%), unless otherwise stated. IQR: interquartile range. BMI: body mass index; NTM: nontuberculous mycobacteria; CPA: chronic pulmonary aspergillosis. ^#: among the 20 target cavities; ^¶: among the 16 patients with at least one target cavity.

Altogether, these results suggest that EBVs could be applicable to NTM and CPA since: 1) only one (4.8%) patient presented lung fibrosis that might prevent lung parenchyma collapse, representing an exclusion criterion for EBV use; 2) 13 (61.9%) patients had a single target large cavity (> 2 cm) to close; 3) nine (56.3%) patients had a single drainage bronchus ventilating the target cavity; and 4) the diameters of drainage bronchi were within the range of available EBV sizes (PulmonX Zephyr valve 4.0–8.5 mm, Olympus valve 5.0–9.0 mm).

Haemoptysis is a potential concern in the setting of NTM and CPA. In this study, almost half of the patients had experienced haemoptysis during their history of infection. Two case reports indicated that in cases of post-tuberculosis cavity-related life-threatening haemoptysis, EBV collapsing the lung segment or lobe causing the bleeding could effectively treat this complication [16, 17]. Thus, EBV-induced pulmonary atelectasis could not only effectively treat the infection but also prevent the risk of haemoptysis in NTM and CPA patients.

Concerning the safety of this collapse therapy, pneumothorax is the main adverse event reported after endoscopic lung volume reduction with EBV (LVRV). It is mainly observed when a significant reduction in target lobe volume is achieved and is linked to a sudden change in lobe volumes. We hypothesise that the incidence of pneumothorax could be lower in cases of cavitary infection because, unlike bulla emphysema, pericavitary consolidation prevents pleural separation. Furthermore, the number of EBVs required in this indication seems lower than that of LVRV (median 1 for collapse therapy compared to 4 in randomised controlled trials evaluating LVRV [10]). This could also reduce the risk of other adverse events linked to EBV (granulomas, post-EBV infections, etc.).

Given the poor prognosis and therapeutic deadlock of NTM and CPA pulmonary infection [1, 2], the confirmed safety of EBVs in controlled trials for emphysema [10], and the potential benefit of EBVs in NTM and CPA as reported in case reports [11], adding EBV to anti-infective therapy warrants assessment in a controlled trial. This study, which highlights the theoretical feasibility of this procedure based on radiological data, is a first step in developing a clinical research project named “Cavitary Lung Infection: Addition of Endobronchic Valve to Anti Infective Therapy” (CAVITY). The objectives of the CAVITY project will be to demonstrate the benefits and tolerance of EBVs in this specific context of chronic cavitary infection. The goal would be to improve NTM and CPA treatment success based on two main criteria: 1) increasing the culture conversion rate (microbiological cure) and 2) preventing relapse after treatment cessation. If these two conditions are met, treatment shortening could be considered.