Copia - Interstitial Lung version 2

MC:Interstitial lung diseases

Gonzalez MD

START

Complications: Pulmonary Hypertension

Identify common signs and symptoms of diffuse interstitial lung diseases. Explain the pathophysiological mechanisms underlying these diseases. Describe the classification, highlighting common types such as idiopathic pulmonary fibrosis, sarcoidosis, and select connective tissue disease-associated interstitial lung diseases. Discuss diagnostic approaches, including imaging and pulmonary function tests. Outline principles of management and treatment options, focusing on disease-specific therapies and supportive care. Discuss the prognosis and potential complications associated with these diseases, including respiratory failure and pulmonary hypertension.

ÍNDICE

Students Resources (Exam focus)

Healthy Lung COPD Interstitial Disease

Healthy Lung COPD Interstitial Disease

Restrictive vs Obstructive

# 1 Inability to expand or loss of elastic recoil of lungs.

#2 Represents airway blockage, there is increased mucus formation, no scarring exists in these diseases.

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Concept: Interstitial Lung Diseases

Interstitial Lung Diseases (ILD): Concept (1)

Interstitial lung disease is an umbrella term for over 200 different diseases Represents the PERMANENT replacement of the structures by connective tissue All ILD is characterised by: PROGRESSIVE inflammation and fibrosis of the ___________ It causes a chronic and IRREVERSIBLE with a poor prognostic outcome (median survival rate 3-5 years if untreated) and reduced quality-of-life (dyspnea) Cryptogenic fibrosing alveolitis/Idiopathic pulmonary fibrosis is the most AGGRESSIVE form of ILD (the most common ILD)

Treatment should focus on removing the exposure....

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Interstitial Lung Diseases: Concept (2)

The 3 to 5 year mortality is 50%

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Interstitial Lung Diseases: Epidemiology

The prevalence of ILD increases with age (highest in 75-80 years - the mean age at diagnosis is 65 years). More common in males than females (3:1) Complication of connective tissue diseases:

• 80% of individuals with systemic sclerosis and antisynthetase syndrome
• 65% with mixed connective tissue disease
• 25% with Sjogren syndrome
• 5% of people with rheumatoid arthritis
• 2% of patients with SLE

The incidence of lung cancer in people with ILD is 3 times higher (adenocarcinoma, squamous)

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Etiology (1)

The lung constitutes the largest surface of the body that is exposed to the outside environment. Pathogens can enter the lung either with inhaled air or via bloodstream

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Exposure to outside environment

Ambient air pollution exposure: the odds is increased 1.62 fold per 40 ppb increment in nitrogen oxide

Besides gases, air contains different concentrations of small particles (10 µm and smaller) that can penetrate deep into the lung. Of most concern are particles smaller than 2.5 µm (PM2.5) because these have been found to reach alveoli and cross into interstitial tissue and blood.

The diameter of foreign particles determines their depth of penetration into lungs.

Treatment should focus on removing the exposure.... (urban pollution???)

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Etiology (2)

The most common causes: A. Occupational agents (inorganic dusts/asbestosis) B. Environmental agents (allergens/hypersensitivity pneumonitis) C. Smoking: lung function restriction increases by 8% for each 10 cigarette pack-years D. Drug-induced pulmonary toxicity and, radiation-induced lung injury E. Complication of connective tissue diseases F. Inherited

(increased likelihood of 1.76-fold)

Ambient air pollution exposure: the odds is increased 1.62 fold per 40 ppb increment in nitrogen oxide

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Etiology (3)

Genetic: polymorphisms affecting genes associated with telomere maintenance and surfactant production (MUC5B--- mucin protein) Immunologic dysregulations: increase in monocytes and Tregs Infections: Hepatitis C virus, CMV

(2% to 5% of patients with ILD have other family members with ILD)

Male gender (1.7 fold increase)

Age: Each 10 years increase in age is associated with a 2.2 times increase

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Etiology:

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Pathogenesis: "Abnormal lung healing"

ILD develops due to: Genetically susceptible individuals (autoinmune disease/autosomal dominant mutations/epigenetics) + Repeated lung injury (environmental, occupational, autoinmune)

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Pathogenesis (Fibroblast via - Inhaled antigens)

A."Susceptible individual" B.Pathogens enter the lung (inhaled/bloodstream) *repetitive exposure) C.Repetitive exposure ----- TGF B release D.Cellular immunity is conducted (interstitium)

E.Abnormal fibroblast proliferation (TGF-B)- (differentiation + activation + increased resistance to apotpsis) D. Myofibroblasts (expansion of extracellular matrix by collagen deposition) with aberrant lung healing E.Loss of normal respiratory membrane architecture ***abnormal scarring + stiffness*** SIMPLIFICATION OF THE LUNG (HONEYCOMB APPEARANCE) F. Impaired gass exchange

Inflammation plays a less dominant role.

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Pathogenesis

Aberrant healing in the context of repetitive alveolar injury Acute inflammation plays a less dominant role.

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Pathogenesis (T-cells & B-cells via - autoinmune diseases)

A. Auto activation of T cells or B cells, or both

B. Cronic inflammation within the lung (accumulation of lymphocytes and macrophages)

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ILD post ARDS: Post-ARDS fibroproliferation

Causes : Sepsis Influenza COVID-19 Pneumonia Trauma Burn injuries Post-ARDS fibrosis typically is not progressive, but nonetheless can be severe The recovery period for post-ARDS fibrosis can take as long as one year and the remaining deficits to lung function persist, but do not progress.

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Pathogenesis: result

ECM Expansion (irreversible)

Normal

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COPD Pathogenesis !!!!!!!!!!!!!!!! IN oposition to ILD

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ILD Pathogenesis (summary):

Interstitium Activation (Abnormal lung healing)

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ILD Pathogenesis (summary):

Frequently involved (myofibroblast)

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ILD Pathogenesis (summary):

NOT frequently observed!!!

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ILD Types

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ILD Types overview (Give importance to environmental origins)

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ILD Types overview

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Clinical setting

CLINICAL SETTING

Common clinical pattern: Progressive exertional dyspnea Persistent nonproductive cough Extrapulmonary symptoms (connective tissue disease) History of occupational exposure Impaired QOL (90%)

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CLINICAL SETTING: systemic manifestations (extrapulmonary)

Common clinical pattern: Progressive exertional dyspnea Persistent nonproductive cough Extrapulmonary symptoms (connective tissue disease) History of occupational exposure

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PAST MEDICAL HISTORY

Prior medication use (antirheumatic drugs, antineoplastics, Oily nose drops) ***Lung disease may occur weeks to years after the drug has been discontinued Irradiation: Symptoms develop approximately months to years following irradiation (eg, Adriamycin, etoposide, gemcitabine, paclitaxel) Exposures to pets (especially any birds), air conditioners, humidifiers, hot tubs, evaporative cooling systems (eg, swamp coolers) Environment: if there has been water damage to walls in the home or work

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MEDICATION HISTORY

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PAST MEDICAL HISTORY

Regular exposure to birds

Hypersensitivity pneumonitis caused by airborne exposure to avian antigens

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PAST MEDICAL HISTORY

Exposure to organic or inorganic products:

• History of construction work (demolition, plumbing, and electrical work).
• Employment in factories and manufacturing plants, the electronics industry, metal working, stone cutting, and mining.
• Specifically inquire about exposure to asbestos, silica, hard metals, and beryllium.

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PAST MEDICAL HISTORY: Occupational exposure

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PAST MEDICAL HISTORY: Occupational exposure

ERSpublications A review of ventilation–perfusion relationships and gas exchange, basic concepts and their relation to clinical cases http://ow.ly/wMUwq

PAST MEDICAL HISTORY

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PAST MEDICAL HISTORY: Occupational exposure

Silica dust Pneumatic drilling Coring with poor ventilation Internal structure demolition

Wood and sanding

Asbestos

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CLINICAL PRESENTATION

Excercise limitation and dyspnea are hallmarks of ILD (limited patient mobility and reduced QOL) Dyspnea is the major source of distress (insidious but progressive) Grading the level of dyspnea is useful as a method to gauge the severity of the disease Sudden worsening of dyspnea, particularly if associated with pleural pain, may indicate a spontaneous pneumothorax (tuberous sclerosis)

Patients with ILD are at increased risk of ARDS

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CLINICAL PRESENTATION

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CLINICAL PRESENTATION

Grading the level of dyspnea is useful as a method to gauge the severity of the disease

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CLINICAL PRESENTATION

Cough – Dry cough ** A productive cough is unusual for most ILDs Hemoptysis The new onset of hemoptysis suggests a complicating malignancy. Extrapulmonary symptoms: Musculoskeletal pain Weakness Fever Joint pains or swelling Photosensitivity Raynaud phenomenon pleuritis dry eyes

PE: Lung examination: Crackles or "velcro rales" (90%) Cardiac examination: pulmonary hypertension and cor pulmonale Clubbing (42%) — suggests advanced fibrosis of the lung.

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What is nail clubbing?

A. Nail dystrophy, is characterized by lamellar splitting of the free edge of the nail

B. Nail shedding that leads to the embedding of the proximal nail plate into the proximal nail fold with subsequent inflammation

C. The nail plate from the proximal nail fold is deviated by a full-thickness sulcus

D. Nail bed hypervascularization

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Schamroth sign

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Schamroth sign

Clubbing is a clinical finding characterized by bulbous fusiform enlargement of the distal portion of a digit

When the profile of the distal digit is viewed, the angle made by the proximal nail fold and nail plate (Lovibond angle) typically is less than or equal to 160 degrees. In clubbing, the angle flattens out

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Family History & Approach

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Idiopathic pulmonary fibrosis (histology)

Chronic and progressive respiratory failure due to lung fibrosis Fibroblastic foci Dense fibrosis with architectural distortion

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Coal workers´pneumoconiosis

Simple coal workers' pneumoconiosis (CWP)Patients have coal macules (1 - 2 mm collections of carbon laden macrophages) and coal nodules scattered throughout lung, more in upper lobe and upper lower lobe, near respiratory bronchioles

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Diagnostic Methods

Diagnostic Methods: Biomarkers + Function tests + Imaging

1. Initial investigations include blood tests
2. Radiological work up --- Chest radiographs is the first radiological investigation in ILD
3. High-resolution computerised tomography of the thorax (lung window)

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Xray

Fine reticulation in the basal part of the lung (diffuse thickening of alveolar septa, septal fibrosis and mild interstitial inflammation)

Linear opacities in the periphery of the lung that extend to the pleural surface

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Pulmonary function testing

Spirometry and lung volumes: AIRFLOW LIMITATION Most of the interstitial disorders have a restrictive defect with reductions in total lung capacity (TLC), functional residual capacity (FRC), and residual volume (RV) Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) are decreased The FEV1/FVC ratio is usually normal or increased The reductions in lung volumes become more pronounced as lung stiffness increases with disease progression

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Pulmonary Function tests

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Diagnostic Methods: CT SCAN

Reticular HYPERDENSITIES which are small curvilinear lines often located in the periphery of the lung; honeycomb change: clusters of small cysts located likely representing dilated distal ends of small bronchioles

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Diagnostic Methods: Chest Imaging

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Diagnostic Methods

Lung biopsy and bronchoscopy tend to be reserved for the minority of cases where other assessments are inconclusive.

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Fine Asbestosis

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Management

Antifibrotic Pirfenidone is an orally administered small molecule pyridinederivative with anti-inflammatory, antioxidant, and antifibrotic properties.

Immunomodulatory tocilizumab did not significantly improve the primary outcome of 48-week change in modified Rodnan Skin Score.

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Management

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Management

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Palliative care

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The interstitium is certainly more than “mere fibers on the alveolar wall”

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