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 Table of Contents  
REVIEW ARTICLE
Year : 2021  |  Volume : 16  |  Issue : 5  |  Page : 79-86

Role of interventions in diagnosis and management of lung disorders in rheumatic diseases


Department of Pulmonary Medicine, Yashoda Super Speciality Hospitals, Hyderabad, Telangana, India

Date of Submission14-Sep-2021
Date of Acceptance01-Nov-2021
Date of Web Publication21-Dec-2021

Correspondence Address:
Dr. Venkata Nagarjuna Maturu
Department of Pulmonary Medicine, Yashoda Super Speciality Hospitals, Rajbhavan Road, Somajiguda, Hyderabad, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-3698.332981

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  Abstract 


Pulmonary manifestations of rheumatic diseases are common and lead to significant morbidity. Rheumatic diseases can affect the lung parenchyma, the interstitium, airways, pleura as well as the mediastinum. The pulmonary manifestation can be a part of the active disease, or be because of infectious complications, drug-induced changes, or pulmonary manifestations of other organ failure. It is hence important to diagnose early and appropriately, and treat aggressively. Interventional Pulmonology, a subspecialty of pulmonary medicine helps in diagnosis of these pulmonary manifestations. Interventional pulmonology procedures also help to treat central airway obstruction. Various modalities like bronchoscopy, endobronchial ultrasonography and thoracoscopy are now available. This article focuses on these modalities, the procedures which can be performed (bronchoalveolar lavage, endobronchial biopsy, forceps and cryo transbronchial lung biopsies, transbronchial needle aspiration) and the indications for the same.

Keywords: Bronchoscopy, endobronchial ultrasonography, interstitial lung disease, interventional pulmonology, lung biopsy


How to cite this article:
Maturu VN, Vaddepally CR, Prasad V P. Role of interventions in diagnosis and management of lung disorders in rheumatic diseases. Indian J Rheumatol 2021;16, Suppl S1:79-86

How to cite this URL:
Maturu VN, Vaddepally CR, Prasad V P. Role of interventions in diagnosis and management of lung disorders in rheumatic diseases. Indian J Rheumatol [serial online] 2021 [cited 2022 May 28];16, Suppl S1:79-86. Available from: https://www.indianjrheumatol.com/text.asp?2021/16/5/79/332981



Interventional Pulmonology is a rapidly evolving subspecialty in pulmonology. Bronchoscopy (flexible and rigid) and thoracoscopy are increasingly being utilized both for the diagnosis and management of various lung diseases. This chapter shall focus on the role of these techniques in the management of rheumatic lung diseases. Interventional pulmonology procedures can be broadly classified as either being diagnostic, or those performed therapeutically.


  Diagnostic Bronchoscopy Top


Lung involvement in rheumatic diseases can be because of several mechanisms– (a) direct involvement due to the disease process, (b) infections secondary to disease-induced or drug-induced immune suppression,[1] (c) drug-induced pulmonary diseases, or (d) lung involvement due to the disease in other organ systems (cardiac, renal). Many of these can have similar clinicoradiologic appearances [Table 1]. Identifying the correct cause for lung involvement is the first step in managing these conditions. Diagnostic bronchoscopy helps in differentiating these processes.
Table 1: Radiologic patterns and the possible causes for the pattern

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Various interventional procedures have been described, each with specific indications. Some of the interventional procedures which are routinely performed include:

  1. Inspection of the tracheobronchial tree
  2. Broncho-alveolar lavage (BAL)
  3. Lung biopsy
  4. Endobronchial biopsy (EBBx)
  5. Mediastinal lymph nodal biopsy
  6. Radial endobronchial ultrasound-guided nodule biopsy.


Inspection of the tracheobronchial tree

Direct examination of the tracheobronchial tree is the first step during routine bronchoscopy. Some rheumatic diseases have characteristic video bronchoscopic appearances [Figure 1], and this helps in diagnosis. Some of the characteristic appearances of the tracheobronchial tree in rheumatic diseases include:
Figure 1: (a) Image showing critical tracheal stenosis with a tracheostomy tube below the stenotic segment in a case of granulomatosis with polyangiitis, (b) Image showing fine endobronchial nodularity in a case of sarcoidosis, (c) Image showing mucosal oedema sparing the posterior tracheal wall in a case of relapsing polychondritis, (d) Image showing purulent secretions in the bilateral bronchial tree in a case of lupus

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  • Tracheobronchial stenosis – Visualized as a narrowing of the lumen of the trachea or the bronchi. Usually seen in granulomatosis with polyangiitis[2] (subglottic region) and relapsing polychondritis.
  • Endobronchial mucosal granularity – A subset of patients with sarcoidosis have typical granular endobronchial mucosa. There is a high yield of granulomas when an EBBx is performed in the presence of this mucosal granularity.[3]
  • Mucosal edema and narrowing sparing the posterior tracheal wall – Edema of the tracheal wall sparing the posterior wall is characteristic of relapsing polychondritis.[4] The posterior tracheal wall is membranous and doesn't have cartilage.
  • Purulent secretions– The presence of purulent secretions in the tracheobronchial tree is an indication of secondary infection, and should prompt the bronchoscopist to perform BAL or a bronchial wash.


Bronchoalveolar lavage

BAL is the process by which samples (fluid aliquots) from the alveoli are collected for analysis. The collected fluid can be processed for cell counts and microbiologic analysis. It is a simple outpatient procedure and can be safely performed in a vast majority of the centers. In this procedure, the bronchoscope is wedged into a segmental bronchus, 3–5 aliquots of 60–100 ml saline are instilled into the segment, and the fluid is aspirated back into the collection chamber for analysis. The BAL is considered to be representative of the alveolar sample and is hence indicative of the disease process in the alveoli.

In healthy individuals, alveolar macrophages constitute up to 80% of the cells in the BAL fluid, lymphocytes usually constitute 5-15%, neutrophils 2-3% and eosinophils <1%. BAL cell differential count with >15% lymphocytes, >3% neutrophils or >1% eosinophils is considered abnormal.[5]

BAL is not indicated for all patients with suspected connective tissue disease (CTD) related lung diseases.[6] The role of BAL in the evaluation of CTD-interstitial lung disease (ILD) is limited to:

  • Diagnosis of pulmonary infections: For patients with presumed CTD-ILD, BAL is now considered an important tool for diagnosing pulmonary infections in people who cannot expectorate sputum for analysis. The BAL fluid can be tested for the presence of bacteria, mycobacteria and fungal infections by using appropriate smears, culture techniques or polymerase chain reaction panels
  • Diagnosis of diffuse alveolar hemorrhage (DAH): In patients with suspected DAH, BAL can be diagnostic.[7] Serial BAL aliquots showing increasingly bloody return is suggestive of alveolar hemorrhage. Similarly, the presence of >20% hemosiderin-laden macrophages (siderophages) is also indicative of an alveolar hemorrhage. BAL can confirm the diagnosis of an alveolar hemorrhage but may not identify the cause of the hemorrhage
  • Identifying the presence of active disease (alveolitis): The presence of an increased percentage of neutrophils or lymphocytes is often found in patients with ILD and this is referred to as alveolitis. It reflects an ongoing inflammatory process in the alveoli. In scleroderma ILD, the presence of alveolitis is associated with poorer lung function as determined by pulmonary function testing and high resolution computed tomographic (HRCT) scores.[8] However, there is insufficient evidence to suggest BAL as an independent predictor of outcome in patients with ILD[9]
  • Diagnosis of sarcoidosis: In patients with suspected sarcoid-related ILD, the presence of BAL lymphocytosis with an elevated CD4:CD8 ratio (>3.5) is considered to be specific for diagnosis. However, this finding is not universal (sensitivity of 50-60% only),[10] and in long-standing fibrotic sarcoidosis, the ratio returns to normal with an increase in the percentage of neutrophils
  • Diagnosis of drug-induced ILD: Hypersensitivity pneumonitis is one of the rare complications encountered with drugs like methotrexate. The presence of BAL lymphocytosis with low CD4:CD8 ratio, or presence of BAL eosinophilia (>25%), in the setting of new drug exposure, supports the diagnosis of a drug-induced ILD.[11]


Endobronchial biopsy

The role of EBBx in the workup of patients with CTD is limited. It is mainly helpful in the diagnosis of sarcoidosis. Four to six bronchoscopic mucosal biopsies are obtained from sites where the mucosa appears abnormal, or from the carina (in patients with normal-appearing bronchial mucosa). Even if mucosa appears normal on visualization, a biopsy can show nonnecrotic granulomas in up to 30% of the patients.[12] Diagnostic yield of EBBx is significantly higher in patients with visible endobronchial abnormalities when compared with those in normal-appearing mucosa (75% vs. 40%).[3] Adding EBBx to lung biopsy increases the diagnostic yield by 10-20%.[13] Combination of transbronchial needle aspiration (TBNA) with transbronchial lung biopsy (TBLB) and EBBx gives the highest diagnostic yield (up to 90%) in the diagnosis of sarcoidosis.[3]

Transbronchial lung biopsy

ILD is one of the most common forms of lung involvement in CTDs. There are several histologic patterns of ILD. Some of the common patterns are nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), and organizing pneumonia (OP). Each pattern has unique HRCT and histopathologic findings. Histologic pattern identification is possible by examining biopsy specimens obtained from the lung. Pattern identification and lung biopsy are important when HRCT findings are indeterminate. HRCT features are diagnostic for UIP pattern, and hence, when HRCT shows a UIP pattern, a lung biopsy is not necessary. For other patterns of ILD, a lung biopsy is required to confirm the pattern. Lung biopsy also helps to:

  • Prognostication – Each histologic pattern of ILD has a different prognosis. In idiopathic interstitial pneumonia (IIP), the UIP pattern is considered to have poorer outcomes as compared to other patterns. CTD-ILDs have better prognosis as compared to IIP.[14]
  • Identifying fibrotic lung diseases – It is important to identify fibrosis in histopathologic specimens, especially in cases where HRCT is indeterminate. A new term “progressively fibrosing ILD (PFILD) had been recognized which encompasses a group of ILDs, with varying etiologies, characterized by progressively worsening nature and the presence of fibrosis (documented by radiology or histopathology).[15],[16] Anti fibrotic medicine, nintedanib has now been approved as an add on medicine in this subgroup of patients with PFILD[17]
  • Diagnosing interstitial pneumonia with autoimmune features (IPAF): A subset of patients with autoimmune diseases have ILD as the presenting manifestation.[18] This group of patients are identified to have IPAF either clinically and/or by positive serologic tests and/or histologic features suggestive of autoimmunity. Histopathologic features suggesting an autoimmune process include the presence of lymphoplasmacytic infiltrates, interstitial lymphoid follicles with germinal centers, or the presence of an NSIP pattern or an OP pattern.[19] A lung biopsy can help in identifying these histopathologic features.


There are several techniques to obtain lung biopsy. Although the gold standard remains a surgical lung biopsy (SLB), this is not often performed because of the higher morbidity associated with the procedure. TBLB, a bronchoscopic technique in which 4–6 lung biopsy samples are obtained is an alternative to SLB. There are two bronchoscopic techniques by which lung can be biopsied:

  1. Transbronchial forceps lung biopsy (TBFB)
  2. Transbronchial lung cryobiopsy (TBCB)


Transbronchial forceps lung biopsy

A forceps biopsy is performed through a flexible bronchoscope. An alligator or cup forceps is introduced into the working channel of the bronchoscope and the biopsy is obtained. The tissue obtained through TBFB is usually small and the diagnostic yield for ILDs is less (25%–50%). The small size of the biopsy specimen (2–3 mm) and the presence of crush artifact limit the role of TBFB in the workup of fibrotic ILDs.[20] The diagnostic yield of TBFB is better in ILD with bronchocentric involvement, such as sarcoidosis[3] and OP.[21]

Transbronchial lung cryobiopsy

Cryoprobe is a new tool in interventional pulmonology and cryobiopsy (TBCB) has revolutionized the approach to ILDs [Figure 2]. TBCB has now replaced SLB as the initial modality for lung biopsy in cases with suspected ILD.[22]
Figure 2: Current diagnostic algorithm for undiagnosed interstitial lung diseases

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Technique

The cryoprobe is inserted into the desired bronchoscopic segment via a flexible bronchoscope, and the probe is activated for 4–6 s [Figure 3]. During this activation time, the surrounding lung parenchyma gets adhered to the probe (cryoadhesion property due to the Joule Thompson effect). After the activation, the cryoprobe is swiftly removed and the lung parenchyma which is attached to the probe is collected as the biopsy sample. To prevent spillover of blood into other segments, the procedure is usually conducted using an artificial airway and a balloon blocker.[23] Fluoroscopy guidance is used to minimize the risk of pneumothorax.[23] The risk of bleeding and pneumothorax with TBCB is 6.8% and 0.3% respectively.[24]
Figure 3: (a) ERBE flexible cryoprobe (available in 1.7,1.9 and 2.4 mm diameters), (b) Cryoprobes after activation in water, with water frozen to the tip of the cryoprobe, (c) ERBE cryo station with CO2 cryogen gas cylinder, (d) Cryoprobe passed into the segmental bronchus for activation, (e) Fogarty occlusion balloon inflated after the Cryobiopsy to prevent spill-over of bleed into other segments, (f) Fluoro guidance being used while performing cryobiopsy, (g) Picture comparing the smaller size of TBFB specimen (upper container) with that of TBCB specimen (lower container), (h) Image showing the size of TBCB biopsy specimens, each averaging 5 mm in diameter

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Advantages

The biopsy specimen obtained is larger than the TBFB (5–8 mm in diameter).[23] In addition, the biopsy is free from crush artifact. Hence, the diagnostic yield of TBCB is much superior to a conventional forceps biopsy (75–90% vs. 40–50%).[25],[26] As compared to SLB, TBCB offers a similar diagnostic yield, with a shorter hospitalization duration, lesser risk of adverse events, at a lower cost.[27]

Mediastinal lymph node sampling

In rheumatic diseases, especially sarcoidosis where mediastinal nodal enlargement is often the presenting feature, sampling the mediastinal lymph nodes is an essential step in confirming the diagnosis. Linear or convex probe endobronchial ultrasound-guided TBNA (EBUS-TBNA) is now considered the investigation of choice for sampling mediastinal lymph nodes.[28] This has replaced surgical mediastinoscopy as the initial diagnostic modality. Some of the common causes of enlarged mediastinal nodes include tuberculosis, sarcoidosis, and malignancy.

Technique: Linear EBUS TBNA is performed using a dedicated EBUS scope, which has an ultrasound transducer at the tip [Figure 4]. This scope helps visualize the paratracheal and peri-bronchial lymph nodes, and while visualizing the node, real-time needle aspiration of the lymph nodes can be performed. Rapid on-site evaluation (ROSE) of the sample by an on-site pathologist further helps to increase the diagnostic yield.[29] Technologic advances in EBUS, help in procuring a biopsy sample from the lymph nodes. Several techniques have been proposed, and these include EBUS intranodal forceps biopsy,[30],[31] EBUS cryo biopsy and EBUS core biopsy using special needles such as the ACQUIRE franseen[32] and the PROCORE needles.[33],[34] These techniques are helpful, in cases where the ROSE is inconclusive. The current diagnostic algorithm for sampling mediastinal lymph nodes is shown in [Figure 5].
Figure 4: (a) Image showing an Olympus linear endobronchial ultrasound scope with the transbronchial aspiration needle, (b) Image of endobronchial ultrasound TBNA being performed from a sub-centimetric mediastinal lymph node, the needle can be seen real-time while performing the aspiration, (c) endobronchial ultrasound image of the right paratracheal node with superior vena cava distal to then node (asterisk), (d) endobronchial ultrasound image of a hilar node with the hilar vessel (asterisk), (e) endobronchial ultrasound image of the subcarinal node

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Figure 5: Current diagnostic algorithm for sampling mediastinal lymph nodes (EBUS: endobronchial ultrasound, TBNA: Endobronchial ultrasound-guided transbronchial needle aspiration, ROSE: Rapid On-site evaluation, TBFB: Transbronchial forceps biopsy)

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Advantages: The diagnostic yield of EBUS TBNA in diagnosing mediastinal sarcoidosis is high (85–95%),[35] and the procedure is safe with very little morbidity and no mortality.[36] All the mediastinal lymph nodal stations, except stations 5 and 6 (para-aortic and sub-aortic stations), can be accessed while performing EBUS TBNA. It can be performed as a daycare procedure and does not require hospitalization. The aspirate specimen can also be processed for microbiologic tests and molecular tests, as deemed necessary.

Radial probe EBUS-guided sampling of the peripheral lung nodules

Peripheral lung nodules and masses are often a presenting feature of diseases like vasculitis. Such nodules can also develop when on immunosuppressive therapy and can be because of opportunistic infections such as tuberculosis, fungal infections, or nocardiosis. A computed tomography-guided biopsy can be performed for such lesions if they are close to the pleura. Radial EBUS-guided sampling is the bronchoscopic technique of choice for sampling such lesions when CT guided biopsy is not feasible or is inconclusive.

Technique: Radial EBUS probe can be passed through the working channel of a conventional bronchoscope and this provides a 360o sonographic vision of the parenchyma surrounding the probe [Figure 6]. The bronchoscope is first negotiated into the desired segment or the sub-segment. The radial EBUS probe is then passed into the working channel of the scope, and the nodule is to be visualized. Once visualized, sampling of the nodule can be performed using a dedicated brush and forceps. Techniques to improve the diagnostic yield of radial EBUS include performing a cryobiopsy from the nodule,[37] using navigational software to reach the nodule[38] and using thin and ultrathin bronchoscopes[39] to reach much distal into the tracheobronchial tree.
Figure 6: Multimodality diagnostic approach to sampling a peripheral lung nodule: (a) Image showing radial endobronchial ultrasound and the guide sheath passed through the working channel of the adult bronchoscope; (b) high resolution computed tomographic image showing a peripheral lung mass in left upper lobe (arrow); (c) Radial endobronchial ultrasound image of the target lesion showing an eccentric nodule; (d) Virtual bronchoscopic navigation performed using Lung Point system to navigate the bronchoscope to the nodule. Image showing real-time synchronization of the bronchoscopic image and the virtual path generated by the software; (e) Cryoprobe lung biopsy being performed from the lesion under fluoroscopic guidance

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Advantages: The diagnostic yield of radial EBUS to diagnose a peripheral lung nodule is around 70–80%.[40] It is however much safer than a CT guided biopsy with a lower risk of pneumothorax and bleeding. Adding new modalities such as a cryobiopsy will further increase the yield in cases where the visualized lesion is eccentric.[41]


  Therapeutic Bronchoscopy Top


Interventional pulmonology also helps in managing critical central airway obstruction, due to diseases such as granulomatosis with polyangiitis or relapsing polychondritis. Rigid bronchoscopy assisted tracheobronchial dilation can be performed in patients with symptomatic central airway obstruction. Various accessories which assist in controlled dilation of the airways include an electrocautery knife and controlled radial expansion balloons. In certain instances, where the chance of restenosis is high, tracheal silicone or metallic stents can be placed to relieve the obstruction [Figure 7] and [Figure 8]. Such procedures however need technical expertise and are to be performed at centers that are equipped for the same.
Figure 7: Rigid bronchoscopic dilation of critical tracheal stenosis in a case of granulomatosis with polyangiitis. (a) Bronchoscopic image showing critical narrowing of the tracheal lumen, (b) Electrocautery cuts being given using a cautery knife, (c) Serial tracheal dilation being performed using controlled radial expansion balloons, (d) Bronchoscopic image postprocedure showing well expanded tracheal lumen

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Figure 8: Tracheal stent (s) placement in cases of central airway obstruction. (a) Image showing tracheal lumen narrowing due to mucosal oedema/thickening in a case of relapsing polychondritis, (b) Image after metallic Y self-expanding metallic stent placement to relieve central airway obstruction, (c) Fluoroscopic image of the Y stent in position, (d) Bronchoscopic image of a patient with multi-level tracheal stenosis, (e) Image after placement of a straight silicone stent in the trachea, (f) X-ray neck lateral view showing silicone tracheal stent in position

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Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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