Interstitial Lung Disease
ILOs
At the end of this session, the student will be able to:
• Describe the entity of Interstitial lung diseases.
• Understand the pathophysiology of ILDs.
• Classify types of ILDs.
• Explain the clinical picture of ILDs.
• Outline the diagnostic approach of ILDs.
• Classify types and causes of thyroiditis.
• Recognize the definition of Interstitial pulmonary fibrosis.
• Summarize the management plan of ILDs.
•
▪ Interstitial Lung Disease
Interstitial lung diseases (ILD) or diffuse parenchymal lung diseases (DPLD)
comprise a large number of disorders. Interstitial lung diseases are a group of
diseases whose diagnosis in many cases need a high suspicion index.
ILD affects the lung interstitium, which is the tissue and space around the air sacs
of the lungs; it concerns alveolar epithelium, pulmonary capillary endothelium,
basement membrane perivascular and perilymphatic tissues.
▪ Nomenclature:
Diffuse parenchymal lung disease (DPLD)
The term interstitial is misleading since most of these disorders are also associated
with extensive alterations of alveolar and airway architecture.
▪ Pathophysiology:
For many years, IPF was considered a principally inflammatory disease, given the
increase in inflammatory cells in the lungs.
However, growing evidence indicates that IPF is an epithelial-driven disease
whereby an aberrantly activated lung epithelium produces mediators of fibroblast
migration, proliferation, and differentiation into active myofibroblasts.
These myofibroblasts secrete exaggerated amounts of extracellular matrix (ECM)
that subsequently remodel the lung architecture
▪ The convergence of three elements
Agenetic architecture affecting epithelial cell integrity, environmental factors,and
accelerated aging-associated changes promotes epithelial cell activation in idiopathic
pulmonary fibrosis (IPF), which might or might not be exacerbated by injury.
• Classification:
• Clinical picture:
Symptoms:
• Asymptomatic with abnormal findings on radiographs or pulmonary functions.
• Symptoms are non-specific, subtle, and progressive.
• Progressive exertional dyspnea, later at rest.
• Persistent non-productive cough.
• Concomitant systemic illnesses such as collagen vascular disease.
Signs:
• Dry bibasilar crepitations.
• Clubbing (most common in IPF).
• Cyanosis.
• Hypoxemia, late.
• Signs of right heart failure.(Late in advanced disease)
• Diagnostic approach:
1. Pulmonary functions:
Usually, a restrictive abnormality
▪ Normal FEV1/FVC ratio.
▪ Reduced FEV1, VC and TLC.
▪ Impaired diffusing capacity. (decreased DLCO) ( diffusing capacity of the lung
to transfer CO)
2. High resolution CT scan chest.
HRCT is the gold standard imaging modality for patients with ILD
• Radiological pattern of disease:
▪ -Reticulo / Nodular.
▪ -Alveolar shadows.
▪ -Ground glass opacity.
▪ -Honeycombing and traction bronchiectasis.
▪ -Interlobar septal thickening.
3. Arterial blood gases:
Early hypoxia, hypocapnia and late hypoxia hypercapnea.
4. Bronchoalveolar lavage:
Differential cell count of BAL:
• Sarcoidosis: lymphocytosis , T-helper cells & high CD4/CD8 ratio.
• Hypersensitivity Pneumonitis: marked T lymphocytosis/ CD8.
• IPF: increases in neutrophils and eosinophils.
5. Lung biopsy:
▪ Transbronchial lung biopsy:
o Minimally invasive, performed at the same time as BAL.
Useful in the diagnosis of some ILDs e.g. sarcoidosis, infection or lymphangitis
carcinomatosis.
o The use of endobronchial ultrasound (EBUS) is useful in reaching the target area and
decreasing the risk of bleeding and pneumothorax.
▪ TBCx provides larger specimens with fewer artefacts than regular forceps
transbronchial biopsies.
▪ TBCx specimens are largely comparable to SLB, although the TBCx diagnostic
yield falls short of that for SLB (80% for TBCx versus >90% for SLB), so TBCx
has the potential to remove the need for surgery for a large proportion of patients.
▪ This is important, because the complication rate and mortality from cryobiopsy
is significantly lower
▪ TBCx is currently the most promising alternative to SLB, but it carries
inherent risks:
▪ The rate of pneumothorax is relatively high, mild bleeding is frequently
observed.
• Percutaneous needle biopsy:
o Under local anesthesia with fluoroscopic, ultrasound or CT guidance.
o Precise sampling from localized areas of abnormality o Small amount of tissue.
o Risk of bleeding & pneumothorax.
• Surgical lung biopsy:
o Technique:
Video-assisted thoracoscopic surgery (VATS) or limited thoracotomy.
o Diagnostic yield (92%), morbidity (2.5%) & mortality (0.3%).
o Histopathologic evaluation has become the basis for the classification of the ILD,
prognostic information, and guide therapy.
o Severe end-stage DPLD or significant concomitant illness may be wise not to
proceed to SLB.
II. The Idiopathic Pulmonary Fibrosis (IPF)
Definition:
IPF is defined as a specific form of chronic, progressive fibrosing interstitial
pneumonia of unknown cause, occurring primarily in older adults, limited to the
lungs, and associated with the histopathologic and/or radiologic pattern of usual
interstitial pneumonia (UIP).
▪ Prevalence is estimated to be slightly greater in men than in women, prevalence
peaks at 65–79 years of age.
▪ Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, fatal, fibrosing
lung disease of unknown cause, with a survival rate lower than that reported for
many common cancer types.
▪ With the 2014 licensing of two new anti-fibrotic IPF drugs (pirfenidone and
nintedanib), accurately diagnosing IPF, and discriminating it from the other
fibrotic DPLDs, are of critical importance in clinical practice.
▪ Suggested risk factors for IPF Although the cause of IPF is unknown, several
risk factors have been suggested:
Clinical presentation of IPF:
Symptoms and clinical signs of IPF often appear gradually and include:
o Slowly progressing dyspnoea
o Non-productive cough
o Dry, inspiratory bibasilar “Velcro-like” fine crepitations.
o Clubbing of fingers
o Abnormal pulmonary function test results, with evidence of restriction and
impaired gas exchange IPF is a debilitating restrictive lung disease, affecting the
patient’s daily routine physical activities.
IPF disease progression is inevitable yet unpredictable.
Acute exacerbations of IPF often have no identifiable cause and result in high
mortality.
Treatment
Recommendations for the management and treatment of IPF:
• To date there is no therapy proven to improve survival or otherwise significantly
modify the clinical course of IPF.
As such, it is recommended that all patients be considered for recruitment to high-
quality clinical trials of therapy and/or for lung transplantation if appropriate.
• Referral to a transplant center for lung transplantation should be made if the disease
is advanced (DLCO < 40% predicted) or progressive (>10% decline in FVC or ≥
15% decline in diffusion during 6 months of follow-up).
1. Pneumococcal and influenza vaccination.
2. Drugs:
a. Corticosteroids
b. Immunosuppressives: e.g. Azathioprine, cyclophosphamide.
c. New antifibrotic agents: Perfinidione, Nintedanib (tyrosine kinase
inhibitor).
3. Supplemental oxygen
4. Pulmonary rehabilitation.
5. Lung transplantation for end-stage disease.
▪ Pirfenidone and nintedanib are approved as monotherapies for treatment of IPF.
▪ Although pirfenidone and nintedanib have both demonstrated efficacy in
reducing rates of disease progression compared with placebo, the disease is
neither stopped nor reversed and patients continue to experience lung function
decline while on treatment
▪ Both agents target the fibrotic cascade, decreasing fibroblast and myofibroblast
production, and accumulation of extracellular matrix.
▪ Pirfenidone and nintedanib are both associated with gastrointestinal adverse
events (AEs), with pirfenidone mainly associated with nausea and nintedanib
mainly associated with diarrhoea.
Conclusion:
• ILDs are a group of complex disorders usually presenting with progressive
dyspnea, restrictive pulmonary physiology ,and an abnormal chest radiograph.
• Because of overlapping signs and symptoms, the evaluation of these patients is
often frustrating; the key to understanding and correctly diagnosing ILD is the
development and utilization of a disciplined evaluation process.