Copia - Interstitial Lung version 2

Gonzalez MD

START

MC:Interstitial lung diseases

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.

Complications: Pulmonary Hypertension

ÍNDICE

Students Resources (Exam focus)

Healthy Lung COPD Interstitial Disease

Healthy Lung COPD Interstitial Disease

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

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

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

Restrictive vs Obstructive

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

Concept: Interstitial Lung Diseases

Treatment should focus on removing the exposure....

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)

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

Interstitial Lung Diseases (ILD): Concept (1)

The 3 to 5 year mortality is 50%

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

Interstitial Lung Diseases: Concept (2)

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)

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

Interstitial Lung Diseases: Epidemiology

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

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

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

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

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

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.

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

Exposure to outside environment

(increased likelihood of 1.76-fold)

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

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

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

Etiology (2)

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

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

Male gender (1.7 fold increase)

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

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

Etiology (3)

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

Etiology:

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

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

Pathogenesis: "Abnormal lung healing"

Inflammation plays a less dominant role.

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

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

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

Pathogenesis (Fibroblast via - Inhaled antigens)

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

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

Pathogenesis

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

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

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

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

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.

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

ILD post ARDS: Post-ARDS fibroproliferation

ECM Expansion (irreversible)

Normal

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

Pathogenesis: result

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

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

Interstitium Activation (Abnormal lung healing)

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

ILD Pathogenesis (summary):

Frequently involved (myofibroblast)

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

ILD Pathogenesis (summary):

NOT frequently observed!!!

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

ILD Pathogenesis (summary):

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

ILD Types

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

ILD Types overview (Give importance to environmental origins)

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

ILD Types overview

Clinical setting

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

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

CLINICAL SETTING

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

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

CLINICAL SETTING: systemic manifestations (extrapulmonary)

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

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

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

MEDICATION HISTORY

Hypersensitivity pneumonitis caused by airborne exposure to avian antigens

Regular exposure to birds

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

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.

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

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: 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: 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

Asbestos

Wood and sanding

Silica dust Pneumatic drilling Coring with poor ventilation Internal structure demolition

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: Occupational exposure

Patients with ILD are at increased risk of ARDS

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)

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

CLINICAL PRESENTATION

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

CLINICAL PRESENTATION

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

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

CLINICAL PRESENTATION

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

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

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

CLINICAL PRESENTATION

D. Nail bed hypervascularization

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

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

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

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

What is nail clubbing?

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

Schamroth sign

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

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

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

Schamroth sign

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

Family History & Approach

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

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

Idiopathic pulmonary fibrosis (histology)

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

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

Coal workers´pneumoconiosis

Diagnostic Methods

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)

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

Diagnostic Methods: Biomarkers + Function tests + Imaging

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

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

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

Xray

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

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

Pulmonary function testing

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

Pulmonary Function tests

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

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

Diagnostic Methods: CT SCAN

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

Diagnostic Methods: Chest Imaging

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

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

Diagnostic Methods

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

Fine Asbestosis

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

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

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

Management

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

Management

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

Management

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

Palliative care

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

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