1. INERSTITIAL LUNG DISEASE
Dr. M. SOFI MD; FRCP (London); FRCPEdin; FRCSEdin

2. Interstitial lung disease: Clinical evaluation
The diffuse parenchymal lung diseases, often collectively referred to as the interstitial lung diseases (ILDs), are a heterogeneous group of disorders that are classified together because of similar clinical, radiographic, physiologic, or pathologic manifestations.
The descriptive term "interstitial" reflects the pathologic appearance that the abnormality begins in the interstitium, but the term is somewhat misleading, as most of these disorders are also associated with extensive alteration of alveolar and airway architecture

5. Interstitial lung disorders: major categories
Idiopathic interstitial pneumonia
Idiopathic pulmonary fibrosis (IPF)
Non-specific interstitial   pneumonia (NSIP)
Cryptogenic organizing   pneumonia (COP)
Respiratory bronchiolitis   interstitial lung disease (RBILD
Desquamative interstitial   pneumonia (DIP)
Acute interstitial pneumonia (AIP)
Connective tissue disease-associated interstitial lung disease (CTD-ILD)
Sarcoidosis
Lymphoid interstitial   pneumonia (LIP)
Hypersensitivity pneumonitis
Iatrogenic pneumonitis/fibrosis (drug-induced ILD, radiation injury)
Eosinophilic ILD (e.g. eosinophilic pneumonia)
Occupational lung disease
Inherited disorders (e.g. familial pulmonary fibrosis, Hermansky-Pudlak syndrome)
Primary disorders (e.g. pulmonary Langerhans cell histiocytosis)

7. Causes ILD Inhaled substances Drug-induced Idiopathic
Inorganic
Silicosis
Asbestosis
Berylliosis
Organic
Hypersensitivity pneumonitis
Drug-induced
Antibiotics
Chemotherapeutic drugs
Antiarrhythmic agents
Statins
Idiopathic
Sarcoidosis
Idiopathic pulmonary fibrosis
Hamman-Rich syndrome
Antisynthetase syndrome
Connective tissue and Autoimmune diseases
Systemic sclerosis
Polymyositis
Dermatomyositis
Systemic lupuserythematosus
Rheumatoid arthritis
Infection
Atypical pneumonia
Pneumocystis pneumonia (PCP)
Tuberculosis
Chlamydia trachomatis
Respiratory Syncytial Virus
Malignancy
Lymphangitic carcinomatosis

8. Investigation is tailored towards the symptoms and signs.
ILD: Diagnosis
Investigation is tailored towards the symptoms and signs.
A proper and detailed history looking for the occupational exposures, and for signs of conditions is the first and probably the most important part of the workup in patients with interstitial lung disease.
Pulmonary function tests usually show a restrictive defect with decreased diffusion capacity (DLCO).
A lung biopsy is required if the clinical history and imaging are not clearly suggestive of a specific diagnosis or malignancy cannot otherwise be ruled out.
In cases where a lung biopsy is indicated, a trans-bronchial biopsy is usually unhelpful, and a surgical lung biopsy is often required

9. CLINICAL PRESENTATION: ILD
Patients with ILD present with:
Symptoms of progressive breathlessness with exertion (dyspnea)
Persistent nonproductive cough.
Pulmonary symptoms associated with another disease, such as a connective tissue disease
History of occupational exposure (eg, asbestosis, silicosis)
Age and gender — Some of the ILDs are more common in certain age groups or have a male or female predominance. IPF, also called cryptogenic fibrosing alveolitis are over age 50.
Past medical history
Connective tissue disease
Inflammatory bowel disease
Malignancy might be a clue to an associated ILD
Medications may be associated with ILD, notably amiodarone.
Allergic rhinitis and asthma may implicate chronic eosinophilic pneumonia
Nasal polyposis and asthma may suggest Eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss).

10. Symptoms 
Dyspnea – SOB is a common and grading the level of dyspnea is useful to gauge the severity
Spontaneous pneumothorax is known to occur in:
Langerhans cell histiocytosis
Tuberous sclerosis
Dry cough is common in:
Sarcoidosis
Bronchiolitis obliterans with or without organizing pneumonia
Hemoptysis – may occur in:
Alveolar hemorrhage syndromes
Tuberous sclerosis
Granulomatous vasculitides.
Wheezing – uncommon
Chronic eosinophilic pneumonia
Respiratory bronchiolitis
Chest pain – uncommon RA
SLE
MCTD

11. Physical examination ILD: Usually nonspecific
Lung examination — Crackles or "Velcro rales" are present on chest examination in most forms of ILD Inspiratory high-pitched rhonchi, so-called inspiratory squeaks, heard in patients of bronchiolitis and pulmonary fibrosis. Clubbing — is common in some pulmonary disorders IPF/ Asbestosis) and rare in others (sarcoidosis, hypersensitivity pneumonitis). Cardiac examination — Usually normal except in more advanced stages of pulmonary fibrosis, when findings are cor pulmonale & PHT
Pulmonary hypertension may also be a primary manifestation of some CTD disorders (progressive systemic sclerosis).
Cor pulmonale rare in ILD, when present, is advanced disease.
Extra-pulmonary findings of systemic disease :
Alopecia
Cutaneous sarcoidosis
Gottron's papules
Heliotrope rash
“Mechanics" hands
Muscle weakness
Peripheral neuropathy
Sclerodactyly

12. LABORATORY TESTS: ILD
CBC with differential blood count to check for evidence of anemia, polycythemia, leukocytosis, or eosinophilia
Liver function tests: ALT, SGPT, AST, SGOT
Tests for possible rheumatic disease
Antinuclear antibody (ANA)
Rheumatoid factor (RF)
Hepatitis serology
HIV testing may be appropriate.
Sicca features or
positive anti-extractable nuclear antigen (ENA)
anti-RO (SS-A)
anti-La (SS-B)
anti-ribonucleoprotein (RNP)
serum protein electrophoresis
Coagulation studies
anti-glomerular basement membrane (GBM) antibodies
antiphospholipid antibodies,
Urinalysis

13. LABORATORY TESTS: ILD Serum celiac panel Serum IgA endomysial
Additional possible tests for rheumatic disease*
Anti-cyclic citrullinated peptide (Anti-CCP)
Creatine kinase (CK)
Anti-Jo-1 antibody
Anti-neutrophil cytoplasmic antibody (ANCA)
Anti-topoisomerase (Scl-70) antibody, anti-PM-1 (PM-Scl) antibody
Anti-double stranded (ds) DNA antibodies
Serum celiac panel
Serum IgA endomysial
Tissue transglutaminase antibodies in patients who may have idiopathic pulmonary hemosiderosis

14. Chest radiography ILD:
The most common radiographic abnormality on routine chest radiograph is a reticular pattern
Nodular or mixed patterns (alveolar filling and increased interstitial markings) are not unusual
Radiographic finding of honeycombing (small cystic spaces) correlates with pathologic findings
The CXR is normal in 10% of patients with some forms of ILD, particularly those with hypersensitivity pneumonitis
An electrocardiogram is obtained to evaluate for evidence of pulmonary hypertension or concurrent cardiac disease.

15. Chest radiography ILD:
Computed tomography 
 High resolution computed tomography (HRCT) should be obtained in almost all patients with diffuse pulmonary parenchymal disease.
Obtain both supine and prone images to avoid confusing dependent atelectasis with interstitial opacities.
HRCT provides greater diagnostic accuracy than the plain chest radiograph
If heart failure is suspected, a serum brain natriuretic peptide (BNP) level is measured.
An echocardiogram is also obtained when there is suspicion for heart failure or pulmonary hypertension.

16. High-resolution chest CT scan of patient with bilateral reticular and nodular interstitial infiltrates with upper zone predominance.
Frontal chest radiograph demonstrating bilateral reticular and nodular interstitial infiltrates with upper zone predominance.

17. Bilateral nodular and reticular shadows of interstitial lung disease.
Normal chest radiograph
Nodular and Reticular opacities
Bilateral nodular and reticular shadows of interstitial lung disease.
Postero-anterior view of a normal chest radiograph.

18. PULMONARY FUNCTION TESTING:
Spirometry and lung volumes — Most of the ILDs have a restrictive defect with reductions TLC, FRC, RV
Diffusing capacity — A reduction in the diffusing capacity (DLCO) is a common, but nonspecific finding in ILD.

19. PULMONARY FUNCTION TESTING: ILD
Gas exchange at rest and on exertion — 
Resting ABG may be normal in early ILD or may reveal hypoxemia (secondary to mismatching of ventilation to perfusion) and respiratory alkalosis.
Carbon dioxide retention is rare and usually a manifestation of end-stage disease.
Broncho-alveolar lavage:
The patients with an acute onset of ILD will undergo BAL to evaluate for:
acute eosinophilic pneumonia
alveolar hemorrhage
malignancy, and
opportunistic or atypical infection
In everyone presenting with hemoptysis and radiographic ILD, BAL is performed promptly to confirm an alveolar source of bleeding

20. ROLE OF LUNG BIOPSY: ILD
When the results of the evaluation do not allow the clinician to make a confident diagnosis of a given type or stage of interstitial lung disease (ILD), lung biopsy may be necessary.
Lung biopsy may also be indicated to exclude neoplastic and infectious processes.
As an example, sarcoidosis can sometimes have a similar HRCT appearance to lymphangitic carcinomatosis or hypersensitivity pneumonitis.
Or, a patient with rheumatoid arthritis might develop ILD due to the underlying disease, drugs used in treatment, or tuberculosis.

21. Treatment: Significant ILD.
The clinical benefits of immunosuppressive therapy appear to be modest and associated with substantial toxicity
The goal of treating ILD is to reduce alveolar and interstitial injury and inflammation, in the hope that progression of interstitial fibrosis will be retarded.
For patients who have respiratory symptoms, abnormal and/or declining pulmonary function, initiating treatment with cyclophosphamide plus low dose glucocorticoids (equivalent of ≤10 mg/day of prednisolone.

22. Treatment: Significant ILD.
Cyclophosphamide can be administered as a monthly intravenous dose (our preference) or as a daily oral dose (eg, ≤2 mg/kg) prednisolone.
After a 12 month course of cyclophosphamide, patients are commonly transitioned to maintenance therapy with mycophenolate, mofetil (eg, 1.5 to 3 g daily, usually in two divided doses).
Patients whose disease is refractory to the above measures may be candidates for rituximab
Selected SSc patients who have severe ILD that is unresponsive to therapy may be referred for lung transplantation.

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