CHRONIC INTERSTITIAL

(RESTRICTIVE INFILTRATIVE)
LUNG DISEASES
DR. NOELLE ORATA
KENYATTA UNIVERSITY
MBChB III
Chronic interstitial lung diseases

• It is a heterogenous group of disorders characterized by bilateral,

often patchy, pulmonary fibrosis mainly affecting the walls of alveoli
• Categorised based on clinicopathological features and characteristic
histology
• Hallmark: reduced lung compliance (stiff lungs), dyspnea, , abnormal
ventilation-perfusion ratio resulting in hypoxia
• CXR: small nodules, irregular lines, or “ground-glass shadows”
Chronic interstitial lung diseases

• With progression, patients may develop respiratory failure,

pulmonary hypertension, and cor-pulmonale

• With advanced disease it results in diffuse scarring and gross

destruction of the lung, referred to as end-stage or “honey-comb”
lung
FIBROSING DISEASES
Idiopathic pulmonary fibrosis
• A.k.a cryptogrnic fibrosing alveolitis
• Patchy , progressive bilateral interstitial fibrosis
• Occurss above 50 years of age
• Males > Females
• Histology: usual interstitial pneumonia (UIP)
• It’s a diagnosis of exclusion
Pathogenesis
• Result of repeated injury and defective repair of alveolar epithelium,
often in a genetically predisposed individual. Genetic studies have
shown a clear connection
• 35% of people show a genetic variant in MUC5B which alters mucin
production
• Surfactant gene mutations
• Link to cellular aging, seen in people over 55 yrs of age
• Chronic GERD has been suspected
Pathogenesis
• It is hypothesized that abnormal epithelial repair at the sites of
chronic injury and inflammation gives rise to exuberant fibroblastic or
myofibroblastic proliferation, leading to characteristic fibroblastic foci.

• Excessive activation of TNF-β

Morphology
• Gross: cobblestone appearance on pleural lung surface
• Cut surface: rubbery, white areas of fibrosis in the lower lobes,
subpleural regions and interlobular septa
• Histology hallmark: patchy interstitial fibrosis, fibroblastic
proliferation. Early and late lesions seen, honeycomb fibrosis,
interstitial inflammation with infiltrate
Clinical features
• Nonproductive cough
• Progreesive dyspnea
• Dry/velcrolike crackles on inspiration
• Radiological findings: subpleural and basilar fibrosis, reticular abnormalities and
honeycombing
• Poor overall prognosis
• Survival: 3 to 5 years
• Treatment: lung transplantation

** read up on differentials**
PNEUMOCONIOSES
• Used to describe lung diseases induced by organic and inorganic
particulate matter, chemical-fumes and vapour induced lung diseases.
• Most common: coal dust, silica and assbestos
Agent Disease Exposure
Coal Dust Simple coal worker’s pneumconioses Coal mining
Complicated coal worker’s pneumconioses
Silica Silicosis Sandblasting, quarrying, stone
cutting, foundry work, ceramics
Asbestos Asbestosis, plueral effusions, pleural plaques or Mining, milling, and fabrication of
diffuse fibrosis, mesothelioma, carcinoma of the lung ores and materials; installation and
and larynx removal of insulation
Pathogenesis
• Reaction to mineral dust depends on size, shape, solubility and
reactivity of particles for example
 5 – 10 micrometers: unlikely to reach distal airway
 < 0.5 micrometers: move into and out of alveoli, without deposition
or injury
1 – 5 micrometers: most significant, gets lodged in bifurcation of
airway
• The pulmonary alveolar macrophage is a key cellular element in the
initiation and perpetuation of inflammation, lung injury and fibrosis
Coal worker’s pneumoconioses
• Coal-dust induced disease
• Lung findings:
asymptomatic anthracosis
Simple coal worker’s pneumoconiosis – deposits without reaction,
macrophage accumulation
Complicated coal worker’s pneumoconioses CWP or progressive
massive fibrosis (PMF) – confluent fibrosing reaction which leads to
extensive fibrosis with lung compromise
Morphology
• Pulmonary anthracosis – pigment engulfed by alveolar of interstitial
macrophages which accumulates in connective tissue along
pulmonary and pleural lymphatics and in draining lymph nodes
• Simple coal worker’s pneumoconiosis – coal macules and coal
nodules, involves upper lobes and upper zones of lower lobes, central
emphysema
• Complicated coal worker’s pneumoconioses CWP or progressive
massive fibrosis (PMF) – multiple dark black scars larger than 2cms up
to 10cms with dense collagen and pigment
Clinical features
• CWP – little decreese in lung function
• PMF – increasing pulmonary dysfunction, pulmonary hypertension
and cor-pulmonale
Silicosis
• Most chronic occuapational disease in the world
• Cause: silica inhalation. 2 forms: crystalline and amorphous
• Crystalline – most toxic and fibrogenic
Morphology
• Gross: silicotic nodules,
• Microscopically: concentrically arranged hyalinized collagen fibres
“whorled appearance”
• Polarized microscopy shows weakly bilateral birefringent silica
Clinical features
SOB late in disease course
PMF presents with pulmonary hypertension and cor-pulmonale
Increased susceptibility to TB
Asbestosis and Asbestos-Related
Diseases
• Occupational exposure leads to:
Parenchymal interstitial fibrosis
Localized fibrous plaques/diffuse fibrosis in the pleura
Pleural effusions
Lung carcinoma
Malignant pleural and peritoneal mesothelioma
Laryngeal carcinoma
Pathogenesis
• Asbestos activates inflammation in and macrophages, damage
phagolysosomal membrane, stimulating release of pro-inflammatory
factors and fibrogenic mediators
• Also acts as a tumour inititator and promoter
Morphology
• Diffuse pulmonary interstitial fibrosis characterized by presence of
asbestos bodies
• Begins in lower lobes and subpleurally, spreads to middle and upper
lobes as fibrosis progresses.
• Contraction of fibrous tissue distorts normal architecture creating large
air spaces within thick fibrous walls leading to the honeycombed
pattern
• Pleural adhesions, pulmonary hypertension and cor-pulmonale
• Hallmark: pleural plaques – dense well circumscribed collagen with
Ca2+ on anterior and posterolateral aspects of pleura
Clinical feature
• Worsening dyspnea 10 – 20 years post exposure
• Cough and sputum production
• CHF
• Cor-pulmonale
• 5 fold increase of developing lung cancer which has a poor prognosis

• **read pm
Drug and radiation induced pulmonary disease**
GRANULOMATOUS
DISEASES
Sarcoidoses
• It’s a multisystem disease characterized by noncaseating
granulomatous inflammation in many tissues and organs
• Histological diagnosis is done by exclusion
• Major finding at presentation: bilateral hilar lymphadenopathy of lung
involvement (or both), seen on CXRs
Epidemiology
• Affects all genders races and age groups
• Consistent predilection for adults younger than 40 years
• high in Danish and Swedes and African Americans in USA (10 times
higher than whites)
• Higher prevalence in non smokers
Etiology and pathogenesis
• Though to be a disease of disordered immune regulation in
genetically predisposed individuals exposed to certain environmental
agents

• Development of cell mediated immune response to unknown antigen

driven by CD4+ T helper cells
• Recurs in one third of patients who’ve had lung transplant
Morphology
• Nonnecrotizing epithelioid granuloma
• Multinucleate giant cells
• Schaumann bodies
• Asteroid bodies
• Diffuse interstitial fibrosis – honeycomb lung
• Hilar and paratracheal lymph node enlargement in 75-90% of cases
• Skin lesions in 25% of patients –
• Hallmark of acute sarcoidosis: Erythema nodosum
• Involvement of eye and lacrimal glands in 1/5 to ½ of patients in the
form of iriditis or iritis which can lead to glaucoma and corneal
opacities leading to blindness
• Lateral or bilateral parotitis with parotid gland enlargement
• Choroiditis, retinitis and optic nerve involvement
• Mikulicz syndrome
• Spleen has granulomas in ¾ of cases, liver granulomas around portal
triad, bone marrow
• Hypercalcimia and hypercalciuria
Clinical features
• Assymptomatic
• CXR: bilateral hilar adenopathy
• Peripheral lymphadenopathy
• Cutaneous lesions
• Eye involvement
• Splenomegally/hepatomegaly
• SOB, cough
• Fever, fatigue, weight loss, anorexia, night sweats
HYPERSENSITIVITY
PNEUMONITIS
• Its an immunologically mediated inflammatory lung disease that
affects the alveoli a.k.a allergic alveolitis
• Usually due to repeated exposure at work
• Damage occurs at level of alveolus
• Decrease in lung compliance, diffusion capacity and total lung volume
Source of Antigen Types of Exposures
Mushroom, fungi, yeasts Contaminated wood, humidifiers, central hot air
heating ducts, peat, moss plants
Bacteria Farmer’s lung
Mycobacteria Metalworking fluids, hot tub, sauna
Birds Pigeons dove feathers ducks
chemicals Isocyanates, zinc dyes
Morphology
• Patchy mononuclear cell infiltrate in the pulmonary interstitium with
peribronchiolar accentuation
• Lymphocytes, macrophages and plasma cells dominate
• “Loose” poorly formed granulomas without necrosis are present in
more than 2/3rd of the cases
Clinical Features

• Acute reaction: fever, cough, dyspnea, constitutional signs and

symptoms 4-8 hours after exposure
• Chronic disease: cough, dyspnea, malaise and weight loss

• Failure to remove irritant/allergen leads to chronic interstitial

pulmonary disease
Pulmonary eosinophilia
• Pulmonary infiltrates rich in eosinophilia. Has categories:
1. Acute eosinophilic pneumonia with respiratory failure – fever, dyspnea, hypoxi.
CXR: diffuse pulmonary infiltrates >25% eosinophils in bronchoalveolar lavage
2. Simple pulmonary eosinophilia (Loeffler syndrome) transient pulmonary
lesions, eosinophilia in the blood, benign clinical course
3. Tropical eosinophilia – caused by infection by microfilariae and helminthic
parasites
4. Secondary eosinophilia – associated with asthma, drug allergies and certain
forms of vasculitis
5. Idiopathic chronic eosinophilic pneumonia
smoking-related interstitial diseases

• Desquamative interstitial pneumonia (DIP) – accumulation of

smoker’s macrophages in the air spaces, thickened septa with
inflammatory infiltrate, mild interstitial fibrosis. Pulmonary function
tests show mild restrictive abnormality. Have a good prognosis and
good response to steroids and smoking cessation

• Respiratory bronchiolitis – found in smokers, pigmented intraluminal

macrophages. Mild peribronchiolar fibrosis. Have dyspnoea and dry
cough