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

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

Interstitial lung disease (ILD) Interstitial lung disease (ILD), or diffuse parenchymal lung disease (DPLD),is a group of lung diseases affecting the interstitium (the tissue and space around the air sacs of the lungs). It concerns alveolar epithelium, pulmonary capillary endothelium, basement membrane, perivascular and perilymphatic tissues.

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 lupus erythematosus Rheumatoid arthritis Infection Atypical pneumonia Pneumocystis pneumonia (PCP) Tuberculosis Chlamydia trachomatis Respiratory Syncytial Virus Malignancy Lymphangitic carcinomatosis

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

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).

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

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

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

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

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.

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.

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.

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.

PULMONARY FUNCTION TESTING: Spirometry and lung volumes — Most of the ILDs have a restrictive defect with reductions TLC, FRC, RV Interstitial pattern on chest radiograph accompanied by obstructive airflow limitation (i.e., a reduced FEV1/FVC ratio) is suggestive of: Tuberous sclerosis Combined chronic obstructive pulmonary disease (COPD) and ILD Constrictive bronchiolitis Diffusing capacity — A reduction in the diffusing capacity (DLCO) is a common, but nonspecific finding in ILD. The decrease in DLCO is due to effacement of the alveolar capillary units but more importantly to the extent of mismatching of ventilation and perfusion of the alveoli.

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. Bronchoalveolar 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, which can often be diagnosed on the basis of BAL findings In everyone presenting with hemoptysis and radiographic ILD, BAL is performed promptly to confirm an alveolar source of bleeding and identify infectious etiologies, if present

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 with multidisciplinary interpretation of the results 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.

Treatment: Significant ILD. The benefits of immunosuppressive therapy appear to be modest and associated with substantial toxicity. The goal is to reduce alveolar and interstitial injury and inflammation. Steroids For some people, corticosteroids alone may decrease lung inflammation and cause an improvement in symptoms.  Nintendanib It is a triple kinase inhibitor and Like pirfenidone, nintednib slows the progression of disease for some people with IPF. Mycophenolate Used to help reduce the steroids required. It prevents the immune system from attacking cells in the body that result in fibrosis. Azathioprine For intolerable side effects of other medications. It is not typically recommended for treatment of people with IPF Pirfenidone The mechanism is unknown, but it has anti-fibrotic and anti-inflammatory properties. Slows the progression of disease for some people with IPF.

THANK YOU FOR YOUR ATTENTION