Adult Chest Surgery

Chapter 91. Role of the Thoracic Surgeon in the Diagnosis of Interstitial Lung Disease 

Interstitial lung disease (ILD) represents over 200 diagnostic entities. Some are distinct clinicopathologic disorders, whereas others belong to a broader class of clinical syndromes, such as the connective tissue diseases. ILD is characterized by a progressive and diffuse inflammation of the pulmonary interstitium often leading to fibrosis. Patients typically present with chronic respiratory complaints, including dyspnea, and chest radiographic findings that demonstrate pronounced "reticular markings." The distinct clinicopathologic disorders that constitute ILD can vary widely in presentation. Examples include sarcoidosis, eosinophilic pneumonias, idiopathic pulmonary fibrosis, and infectious processes, including tuberculosis. Pulmonary fungal infections are reviewed in Chapter 90.

The primary goal of the thoracic surgeon in the evaluation of patients with symptoms and radiologic findings consistent with ILD is to facilitate an expedient diagnosis. Diagnostic modalities include bronchoscopy, bronchoalveolar lavage, and chest CT scanning. However, lung biopsy by transbronchial, open, or video-assisted thoracic surgery (VATS) techniques remains the most definitive and expeditious means of establishing the diagnosis. Development of VATS techniques has greatly reduced the morbidity associated with lung biopsy, and the technique is readily available at most centers. This chapter provides an overview of the spectrum of disease and diagnostic approach to ILD from the surgical perspective.

PATTERNS OF INTERSTITIAL LUNG DISEASE

The inflammatory response observed in ILD targets the interstitium, which is comprised of the fibrous septa and alveolar walls that give structure to the lungs. Within the interstitium lie the pulmonary vessels, lymphatics, and bronchi. The inflammatory response may be expressed against cells in any or all of these structures (Fig. 91-1). Often it is focused on one component of the interstitium, permitting a loose categorization of two patterns of injury: granulomatous and alveolitic1,2 (Table 91-1).

Figure 91-1.

 

Morphologically, the lung parenchyma has two general components: airspace and interstitium. The airspace is comprised of the respiratory bronchioles, alveolar ducts, and alveoli. The interstitium consists of the fibrous septa, alveolar walls, and connective tissues that surround the vascular and bronchial lumina.

Table 91-1. Categorization of Interstitial Lung Disease into Granulomatous and Alveolitic Subtypes

Granulomatous

Infections—tuberculosis, helminthes, aspergillosis

Sarcoidosis

Granulomatous vasculitides—Wegener's granulomatosis and Churg-Strauss syndrome

Hypersensitivity pneumonitis

Foreign body/Inorganic dust

Eosinophilic pneumonias

Histiocytosis X

Alveolitic

Goodpasture's syndrome

Drug-induced injury

Idiopathic interstitial pneumonias

 

Granulomatous Pattern

The pattern of disease injury denoted as granulomatous is initiated by a cell-mediated immune response to a foreign or self protein. The response is initiated by a release of inflammatory cytokines. Activated immune cells, typically macrophages, then encircle and engulf the material that the immune system has failed to recognize in an antigen-specific fashion. Granulomata that sequester the unrecognized material are formed subsequently. This inflammatory process, once activated, can spread to the alveoli, which renders the pattern of injury difficult to discern in end-stage disease. The granulomatous mechanism is expressed in several pulmonary diseases, which are described briefly below.

INFECTION

Mycobacterium tuberculosis infection is the most common cause of granulomatous lung disease worldwide.3,4 Aspergillus and certain helminths also can lead to pulmonary granulomatous disease(see Chap. 90). Diagnosis relies on history, a positive purified protein derivative test, and sputum culture.

SARCOIDOSIS

Sarcoidosis is a chronic systemic disorder characterized by the presence of granulomata in certain affected organs. The disorder remains poorly understood. Patients with sarcoidosis may have variable and fluctuating symptoms. Classically, patients present with fever, myalgias, chills, fatigue, and weight loss. Diagnosis is often made radiographically by the appearance of bilateral hilar and mediastinal lymph node enlargement on plain chest films, sometimes accompanied by a reticulonodular pulmonary pattern. Most patients diagnosed by chest radiography alone are asymptomatic. Angiotensin-converting enzyme levels are often elevated.

GRANULOMATOUS VASCULITIDES

In Wegener's granulomatosis and Churg-Strauss syndrome—two representative granulomatous vasculitides—the granulomata form around the pulmonary vessels. Wegener's granulomatosis is characterized by the presence of necrotizing granulomata within the pulmonary parenchyma (Fig. 91-2). The renal vasculature also may be involved, and 90% of patients have antibodies to antineutrophil cytoplasmic antibodies against the PR3 serine proteinase (c-ANCA).3,5–10 Churg-Strauss syndrome is a rare systemic disorder characterized by eosinophilia and eosinophilic granulomata of the pulmonary vasculature. Diagnosis of both these diseases rests on clinical suspicion, along with the laboratory studies and pathologic findings indicated earlier.

Figure 91-2.

 

CT scan representative of radiographic findings seen in Wegener's granulomatosis. Note large cavity in the left lung.

HYPERSENSITIVITY PNEUMONITIS

Hypersensitivity pneumonitis is caused by repeated inhalation of dust-containing organic antigens, which leads to diffuse inflammation of the lung parenchyma and airways in previously sensitized patients.11–13 A large number of antigens have been implicated, with diseases named after various interesting occupations (e.g., bagassosis derived from bagasse, or sugarcane dust, cheese washer's lung from handling cheese mold, compost lung). Diagnosis lies in careful history taking, especially when a known occupational exposure is suspected. Early parenchymal changes are characterized by neutrophil and macrophage infiltration of the distal bronchioles and alveoli. Progression to granuloma formation and interstitial fibrosis occurs with continued exposure to the antigen.

FOREIGN BODY/INORGANIC DUST

Exposure to small foreign particles, whether organic or inorganic, can lead to a spectrum of pulmonary disease processes such as those associated with chronic exposure to metal dusts (e.g., beryllium, aluminum, and zirconium) or small organic particles leading to hypersensitivity pneumonitis. Patients may be asymptomatic to the initial exposure but later develop symptoms secondary to occult lung injury.

EOSINOPHILIC PNEUMONIAS

Eosinophilic pneumonia is a pulmonary process characterized by the accumulation of eosinophils within the parenchymal tissues. Eosinophilic pneumonias can be caused by helminth infections, such as Strongyloides stercoralis and Ancylostoma duodenale, and drug allergies.8,14 More often than not, the etiology is unknown. Idiopathic eosinophilic pneumonias have three forms: simple, acute, and chronic. Simple eosinophilic pneumonias are rare, characterized pathologically by an interstitial edema that is abundant with eosinophils and typically resolves spontaneously, particularly with smoking cessation. Patients with acute eosinophilic pneumonia present in severe respiratory distress. Their prognosis is poor. The chronic form is more indolent and often found in patients with a history of asthma. Chronic eosinophilic pneumonia is similar in both histology and, in most cases, radiographic appearance to the simple and acute forms. Diagnosis of all these syndromes requires the demonstration of peripheral blood eosinophilia and often a tissue biopsy.14,15 The disease clears rapidly with steroid treatment, although there is a higher rate of relapse with the acute form.8,14

HISTIOCYTOSIS X

Histiocytosis X is a rare disorder characterized by the peribronchial accumulation of specialized antigen-presenting cells known as Langerhans' cells. Long-standing disease, also known as eosinophilic granulomatosis, can lead to interstitial fibrosis and also may present with skeletal involvement. Tissue biopsy is often required for diagnosis.16 Spontaneous remission can occur, particularly with smoking cessation, although treatment with steroids may be required.

Alveolitic Pattern

The alveolitic categorization of ILD applies when the injury is directed primarily toward the alveolar wall, resulting in airspace disease. Cellular and humoral components of the immune system both may be involved. Alveolitic mechanisms have been implicated in a variety of pulmonary diseases, summarized below1,2 (see Table 91-1).

GOODPASTURE'S SYNDROME

Goodpasture's syndrome is a systemic disease process characterized by pulmonary hemorrhage and glomerulonephritis. It is a rare disorder diagnosed predominantly in young males and is linked to the presence of the HLA-D2 allele. The disease is caused by antibodies directed against a collagen protein found in the alveolar and glomerular membrane, resulting in an antibody-mediated injury.17–19 Patients present with both hemoptysis and hematuria. Diagnosis is based on clinical symptomatology and renal biopsy.18,19

DRUG-INDUCED INJURY

Drug-induced lung injury often results in an alveolitic pattern of injury, whether the mechanism of injury is due to a direct cytotoxic or an immune-mediated injury. Numerous drugs have been implicated in this disease process, including bleomycin, nitrofurantoin, and amiodarone.20 The diagnosis rests on clinical suspicion and correlation with prior drug exposure. Lung biopsy may or may not be helpful because fibrosis becomes apparent only in late-stage disease.

IDIOPATHIC INTERSTITIAL PNEUMONIAS

Idiopathic interstitial pneumonias encompass a range of pulmonary disorders characterized by infiltration of the pulmonary interstitium with immune cells, leading to alveolitic changes. Continued inflammation eventually results in end-stage pulmonary fibrosis (Fig. 91-3). This disease has generated much diagnostic confusion because of the various terms given to this form, including Hamman-Rich disease, idiopathic pulmonary fibrosis, usual interstitial pneumonitis, and diffuse pulmonary alveolar fibrosis. Several subclassification schemes have been proposed, which many argue are superfluous because this disorder can be viewed as a continuum. The most common subclassification, proposed by Averill Liebow, divides idiopathic interstitial pneumonias into six categories: (1) usual interstitial pneumonia/idiopathic pulmonary fibrosis, (2) desquamative interstitial pneumonia, (3) nonspecific interstitial pneumonia, (4) acute interstitial pneumonitis, (5) respiratory bronchiolitis-associated interstitial lung disease, and (6) cryptogenic organizing pneumonia. Patients with this continuum of disorders present with progressive dyspnea in the setting of reticular opacities on plain chest films. Diagnosis of the idiopathic interstitial pneumonia rests on the exclusion of other known disorders and lung biopsy.19,21–25Often, a clear-cut distinction cannot be made between the various subclasses, even with adequate lung biopsy. Lymphocytic interstitial pneumonia is often misidentified as belonging to this category because chest radiographs of patients with lymphocytic interstitial pneumonia often show an "interstitial" pattern of disease. However, lymphocytic interstitial pneumonia is a lymphoproliferative disorder with no alveolar injury, and a lung biopsy may be required to exclude this disorder in some patients.26,27 Patients with progressive disease refractory to immunosuppressive therapy can be treated only by lung transplantation.

Figure 91-3.

 

CT scan from a patient with idiopathic pulmonary fibrosis. Note the significant fibrotic changes and characteristic honeycomb pattern.

CLINICAL PRESENTATION

Patients with ILD typically present with progressive dyspnea, a persistent nonproductive cough, fatigue, and weight loss. Wheezing, hemoptysis, and pleuritic chest pain are rare symptoms in early ILD. Hemoptysis typically is associated with diffuse alveolar hemorrhage syndromes and the granulomatous vasculitides, but not with other forms of ILD. These symptoms occur in the setting of radiographic evidence of interstitial opacities. Although symptoms are typically chronic, an acute presentation is possible, with the allergic responses seen with hypersensitivity pneumonitis, eosinophilic pneumonia, or drug-induced alveolitis.

Patient Evaluation

A thorough history and physical examination are of paramount importance for patients with suspected ILD (Fig. 91-4). The diagnosis is often suggested by a history of environmental/occupational exposures or connective tissue disease. Laboratory studies are used to identify antibodies that might suggest a specific connective tissue disease or the presence of elevated angiotensin-converting enzyme.28 Pulmonary function tests are used to assess the extent of pulmonary dysfunction. ILD is characterized by a restrictive pulmonary physiology with a reduced total lung capacity, functional residual capacity, and residual volume. The diffusing capacity of the lung for carbon monoxide (DLCO) is also impaired. Forced vital capacity and expiratory volume also may be decreased secondary to a low total lung capacity. Chest x-ray and chest CT scan may be helpful in separating "interstitial" from consolidative patterns of disease and in identifying lymphangitic spread of malignancy when an additional mass(es) is present.29 However, chest radiographic findings are nonspecific and are not helpful in discerning the various forms of ILD. Bronchoalveolar lavage can be a useful diagnosis aid for some diseases, including eosinophilic pneumonias and histiocytosis X (Langerhans' cells), where a predominant cell type is found in the lavage fluid. However, most patients require lung biopsy to make a definitive diagnosis.15,24,30

Figure 91-4.

 

Treatment algorithm for interstitial lung disease.

 

Lung biopsy can be performed by open, VATS, or transbronchial technique. Transbronchial biopsy typically is attempted first to rule out an infectious etiology or confirm an obvious clinical diagnosis (e.g., Goodpasture's syndrome or sarcoidosis). Transbronchial biopsy, however, provides inadequate tissue for diagnosing idiopathic interstitial pneumonia. If the diagnosis remains unclear after transbronchial biopsy, surgical biopsy is warranted and is the most effective means of establishing the diagnosis and prognosis. Biopsy should be obtained from two distinct disease sites, preferably from two different lobes with a margin of normal tissue for comparison. Some investigators report that lingual or middle lobe biopsy may overrepresent fibrosis and vasculopathy. Others disagree, reporting that lingual or right middle lobe biopsy is equivalent to biopsy of other pulmonary segments, provided that the area selected for biopsy is representative of the disease process present elsewhere in the lung.31–37 Generally speaking, areas of localized fibrosis or scarring should be avoided and more representative areas selected for biopsy. If an adequate biopsy is performed early in the disease course before the onset of end-stage fibrosis, the diagnostic accuracy approaches 90%.38

VATS biopsy has proved in most series to be as diagnostically accurate as open-lung biopsy performed through a minithoracotomy.39,40 VATS lung biopsy typically is done with the patient in the full lateral decubitus position, with single-lung ventilation accomplished through either a double-lumen endotracheal tube or with a bronchial blocker (Fig. 91-5). Ports are placed with the goal of triangulating the area of interest in the lung (Fig. 91-6). Atraumatic graspers are used to localize the representative lesion, and the sample is resected with endoscopic staplers (Fig. 91-7). The lesion then is removed from the thorax within a specimen bag (Fig. 91-8).

Figure 91-5.

 

Single-lung ventilation by means of a bronchial blocker together with a single-lumen endotracheal tube.

 

Figure 91-6.

 

Ideal port placement for VATS lung biopsy.

 

Figure 91-7.

 

Atraumatic graspers and endoscopic stapler used to localize and resect diseased lung parenchyma.

 

Figure 91-8.

 

The lesion is placed in a specimen bag and removed from the operative field to avoid potential contamination.

After biopsy, the ports are removed and the incisions closed after hemostasis is achieved. An outline of the VATS biopsy technique is presented in Table 91-2. Contraindications to performing a VATS biopsy include (1) patients with advanced-stage disease who may not be able to tolerate single-lung ventilation or a full lateral decubitus position and (2) acutely ill patients and patients with late-stage ILD who often have decreased pulmonary compliance and decreased DLCO, precluding general anesthesia even with two-lung ventilation. For these patients, an expedient open-lung biopsy through a minithoracotomy is the best option. As a general principle, lung biopsy is ideally performed during the early stages of ILD because diffuse fibrosis makes both diagnosis and ventilation much more difficult and may even preclude single-lung ventilation and VATS biopsy. The ideal candidate for VATS is an ILD patient who is symptomatic but ambulatory with preserved lung function.

Table 91-2. Ten Steps to Video-Assisted Thoracoscopic Surgery (VATS) Lung Biopsy

1.     Single-lung ventilation with either placement of double-lumen endotracheal tube or placement of a bronchial blocker together with a single-lumen endotracheal tube (see Fig. 91-5). Bronchoscopic confirmation of correct placement and auscultatory confirmation of lung isolation of the operative side is recommended.

2.     Use the chest CT findings to plan the placement of the patient in the full lateral decubitus position with slight flexion of the operating table to widen the lung interspaces.

3.     Placement of three 10-mm ports with the idea of triangulating the region of lung targeted for biopsy within the three ports. The camera port should be at the apex of the triangle (see Fig. 91-6).

4.     One centimeter skin incisions should be placed in the rib interspaces with Bovie dissection through the soft tissue and intercostal muscles until the endothoracic fascia over the rib is reached. The endothoracic fascia should be divided carefully over the rib to avoid injury to the lung as the thorax is entered.

5.     A 10-mm thorascopic port then is placed into the chest through this incision.

6.     A 10-mm 30-degree camera is inserted through the port into the thoracic cavity, and the thorax is inspected.

7.     The other two 10-mm ports then are placed in a similar fashion with direct visualization of entry into the thoracic cavity.

8.     With the aid of atraumatic grasping instruments (e.g., O-ring forceps), the lung parenchyma is grasped, inspected, and palpated until the parenchymal lesion(s) of interest is identified (see Fig. 91-7).

9.     Endoscopic staplers are used to resect the identified lesion. The lesion then is removed from the thorax within a specimen bag (see Fig. 91-8).

10.  After ensuring that hemostasis has been achieved, the ports are removed from the thorax. The thorascopic ports then are closed with 2-0 absorbable suture for the soft tissue and 3-0 absorbable suture for the skin.

 

 

SUMMARY

The role of the thoracic surgeon in the diagnosis of ILD is key to identifying an appropriate treatment plan. Although ILD, as a group of over 200 disease entities, is a relatively rare disorder, the symptoms can create a great amount of patient discomfort, warranting a swift and expeditious diagnosis. The number of possible diagnostic entities calls for a thorough understanding of the etiology of ILD and a careful clinical and laboratory evaluation, which is best served by open or VATS lung biopsy. Although other diagnostic modalities are available, including chest x-ray, CT scan, and bronchoalveolar lavage, lung biopsy delivers the most definitive answer in the shortest period of time.

EDITOR'S COMMENT

The complexity of interstitial inflammation—and our ignorance of causal mechanisms—is demonstrated by the many descriptive diagnoses in the pulmonary lexicon. To the dismay of anyone learning lung disease, the many acronyms used to categorize pulmonary disease are not explanatory, but rather descriptive. The role of the surgeon is to provide sufficient tissue so that, at minimum, the description is accurate. Of note, the importance of a tissue biopsy is often related to negative information; that is, excluding diagnoses such as lymphangitic cancer or treatable infections.

–SJM

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