SDL 18 - Interstitial Lung Disease BMS16091064 Jonathan

The usual infiltrative opacification in the periphery of the lung in interstitial lung disease.

Introduction
Interstitial lung disease (ILD) is a clinical term for a heterogenous group of acute and
chronic lower respiratory tract disorders with many potential causes.

Clinical and physiologic features common to ILDs include cough, exertional dyspnea,
absence of pulmonary infection or neoplasm, and abnormal pulmonary physiology,
including a restrictive pattern on pulmonary function testing, coexistent airflow
obstruction, decreased diffusing capacity (Dlco), and increased alveolar-arterial
oxygen difference (Pao2-Pao2) at rest or during exertion.

ILDs include acute and chronic lung disorders with variable degrees of pulmonary
inflammation or fibrosis. All of the cellular and soluble constituents that make up the
gas exchange units (alveolar wall, capillaries, alveolar space, and acini) and the
bronchiolar lumen, terminal bronchioles, and pulmonary parenchyma beyond the gas
exchange units (as well as the pleura and lymphatics) are involved.
Clinical Classification of ILDS
Pathophysiology
Interstitial lung diseases are thought to result from an unknown tissue injury and
attempted repair in the lung of a genetically predisposed person. Numerous genetic
variants have been associated with subsets of familial pulmonary fibrosis and with
some sporadic cases. These variants include hTERT or hTR components of the
telomerase gene, the surfactant protein gene, MUC5B, A-kinase anchoring protein 13
(AKAP13) and TOLLIP, among others. About 3 to 4% of patients treated with
programmed cell death-1 inhibitors can develop interstitial lung diseases.

The short telomere syndromes are a group of genetic disorders that are caused by
mutations of the telomerase enzyme and telomere genes. The prevalence of
telomerase mutations in lung disease makes the short telomere syndromes the most
common premature aging disorders, with an estimated 10,000 affected adult
individuals in the United States alone. The most common short telomere syndromes
are interstitial lung diseases, including idiopathic pulmonary fibrosis. About 20% of
patients with familial pulmonary fibrosis have mutations in telomerase enzyme genes.

In idiopathic pulmonary fibrosis, varying degrees of acute, subacute, and chronic

fibroblast proliferation are present in the lungs. Ultimately, progressive fibrosis results
in honeycombing, an end-stage finding that is often associated with increased
pulmonary vascular resistance and secondary pulmonary hypertension. As a reflection
of these dynamic processes, histopathologic examination of lung tissue often reveals
highly heterogeneous findings within the same biopsy specimen.

Clinical Features
ILDs are typically characterized by cough and progressive dyspnea. Pleuritic chest
pain may occur with certain connective tissue or drug-induced ILDs; acute pleuritic
chest pain with dyspnea may represent a spontaneous pneumothorax in association
with lymphangioleiomyomatosis, tuberous sclerosis, neurofibromatosis, or
Langerhans cell histiocytosis. Hemoptysis suggests a diffuse alveolar hemorrhagic
syndrome, systemic lupus erythematosus (SLE), lymphangioleiomyomatosis,
granulomatosis with polyangiitis, or Goodpasture syndrome; it is rare in other ILDs.

In patients with existing ILD, new hemoptysis should prompt consideration of a

superimposed malignancy, pulmonary embolus, or infection such as aspergillosis. In
some patients, the first and the only clue to the presence of an ILD may be the
incidental finding of parenchymal abnormalities in computed tomography (CT)
images of the chest or rales (crackles) on lung auscultation.

A history of wheezing suggests the coexistence of occult hyperactive airways and

airflow obstruction, thereby raising the possibility of allergic bronchopulmonary
aspergillosis, eosinophilic granulomatosis with polyangiitis, chronic eosinophilic
pneumonia, or parasitic infection. In some patients, the initial presentation may be
with peripheral cyanosis, clubbing, or the signs of an underlying systemic disease.
Diagnosis
The first key in patients with an ILD is to establish the syndromic diagnosis and then
pursue the differential diagnosis of its specific cause. However, a conclusive cause
often may not be identified despite an exhaustive medical history and invasive
diagnostic interventions, including bronchoalveolar lavage and bronchoscopic or
surgical lung biopsy specimens.
Diagnotic Approach to ILDs
Drug Induced and Iatrogenic Interstitial Lung Disease
Noninvasive Evaluation
Chest Radiograph

Radiographic Features of Idiopathic ILD

CT Scan
Characteristic Chest Radiograph Patterns in Patients with ILD
Invasive management

Bronchoalveolar lavage
Findings on bronchoalveolar lavage can be diagnostic in some patients with ILD and
can narrow the differential diagnosis in others. For example, a
lymphocyte-predominant cellular pattern raises the possibility of sarcoidosis or
hypersensitivity pneumonitis in the appropriate clinical setting.

Eosinophils may be seen in pulmonary Langerhans cell granulomatosis or

eosinophilic pneumonia, an asbestos body count greater than 1 fiber per milliliter of
bronchoalveolar lavage fluid may be seen in asbestosis, and specially staining
surfactant material may be seen in pulmonary alveolar proteinosis.

Transbronchial lung biopsy

A transbronchial lung biopsy may reveal noncaseating granulomas in
sarcoidosis,“loose” noncaseating granulomas in hypersensitivity pneumonitis, giant
cell granulomas in hard metal pneumoconiosis, or smooth muscle proliferation in
lymphangioleiomyomatosis. However, failure to establish a diagnosis despite
bronchoalveolar lavage and transbronchial lung biopsy does not exclude these entities.
Although larger lung biopsy specimens obtained with transbronchial cryobiopsy may
yield diagnostic histopathologic features, transbronchial cryobiopsy should be
considered in centers with documented expertise.

Thoracoscopic biopsy
Video-assisted thoracoscopic biopsy or open lung biopsy may be required to obtain an
adequate sample for histologic evaluation of a patient with unexplained signs and
symptoms when other studies have failed to establish a diagnosis. The mortality rate
is generally less than 2% when the procedure is performed electively.

Management
When the cause of the ILD is clearly known (e.g., acute or subacute hypersensitivity
pneumonitis, occupational ILD, iatrogenic), further avoidance of the,inciting agent or
agents is essential.

Although systemic corticosteroids are generally indicated and are associated with a
favorable response in,some ILDs, the dosage and duration are unclear and essentially
based on anecdotal,experience.

Supportive oxygen supplementation is dictated by clinical needs. For selected patients

with end-stage ILDs, such as those associated with significant pulmonary,fibrosis and
pulmonary hypertension, lung transplantation may be a viable option. Treatments for
pulmonary hypertension associated with ILDs are indicated in patients
withnconnective tissue diseases,but their clinical benefit for patients with other ILDs
has been disappointing.

Prognosis
In patients with systemic sclerosis (SSc), interstitial lung disease (ILD) predicts
increased mortality patients with severe ILD had a nine-year survival rate of
approximately 30 percent, whereas patients with SSc who did not have severe
involvement of an organ system had a nine-year survival rate of 72 percent.