1. INTERSTITIAL LUNG DISEASE

2. Definition & Background
Interstitial lung disease (ILD) is a common term that includes more than 150 chronic lung disorders. When a person has ILD, the lung is affected in three ways. First, the lung tissue is damaged in some known or unknown way. Second, the walls of the air sacs in the lung become inflamed. Finally, scarring (or fibrosis) begins in the interstitium (or tissue between the air sacs), and the lung becomes stiff.
When the interstitium becomes scarred and thickened, it is much more difficult for oxygen to travel from the air into the bloodstream. Patients with interstitial lung disease, then, will develop symptoms which are the result of lung malfunction,
like shortness of breath and cough.

3. -”without” or “with” granulomas
The terms interstitial lung disease, pulmonary fibrosis, interstitial pulmonary fibrosis, and diffuse parenchymal lung disease often used to describe the same condition.
Classification:
“Known” vs. “Unknown”
-”without” or “with” granulomas

4. Examples of Known Etiology: without granulomas
ARDS
Occupational and environmental inhalants (e.g. asbestos, gases, aerosols)
Drugs
Aspiration
Radiation
Lymphangitic spread of carcinoma

5. Examples of Known Etiology: with granulomas
Occupational and environmental inhalants
-Beryllium
-Hypersensitivity pneumonitis (an allergic disorder)
- Talc
Infectious agents
- AFB (Acid-fast bacillus)
- Fungi

6. Examples of Unknown Etiology: without granulomas
Ideopathic Interstitial Pneumonias (IIP):
Vasculitis
Pulmonary hemorrhage syndromes
Eosinophilic infiltration
Ankylosising spondylitis

7. Examples of Unknown Etiology: with granulomas
Sarcoidosis
Histiocytosis-X
ANCA (+) Granulomatos vasculitis
-Wegener’s granulomatosis
-Churg-Strauss
-Lymphomatoid granulomatosis

8. Clinical Assessment Check medication Employment Systemic Illnesses
Exposures

9. Signs & Symptoms The most common symptoms are shortness of breath
with exercise and a non-productive cough. Some patients
may also have fever, weight loss, fatigue, muscle and
joint pain, and abnormal chest sounds,
depending upon the cause.
Clubbing can also be seen.

10. Pulmonary Function Test
PFT usually shows a restrictive pattern
-The FEV1/FVC ratio is usually normal
-It shows reduced lung volumes (low vital capacity, low total lung capacity)
Arterial blood gases typically show mild hypoxemia.
Patients tend to hyperventilate and have a reduced PCO2 and
compensated respiratory alkalosis, mostly as a result of increased
respiratory rate.

11. Check Medications Immunosuppressive or chemo agents
- Bleomycin, methotrexate, cyclophosphmide
Antibiotics
- Macrobid
Cardivascular drugs
- Amiodarone
Vasoactive and neuroactive
- Sansert and dilantin

12. Occupational ILD There are 3 categories of occupational lung disease
Hypersensitiviy pneumonitis
Organic dusts (byssinosis)
Inorganic dusts (asbestosis, silicosis, coal workers’
pneumoconiosis, and berylliosis)

13. Hypersensitivity Pneumonitis
It is an immune-mediated reaction to organic agents
Typically it has poorly formed granulomas
Diagnosis is by history and chest x-ray may reveal recurrent infiltrates
Various causes include:
Moldy hay --- “farmer’s lung”
Grain dust (works in a grain elevator)
Air conditioning systems
Hobbies such as bird breeding
Best treatment is to remove the patient from the offending antigent. Corticosteroids are beneficial only in acute disease.

14. Byssinosis Caused by inhalation of cotton, flax, or hemp dust.
Not immune-related, no sensitization needed
Early stage has occasional chest tightness
Late stage has regular chest tightness toward the end of the 1st day of the work week (“Monday chest tightness”)
Therapy for early-stage focuses on reversing airway narrowing. Antihistamines may be prescribed to reduce tightness in the chest.
Bronchodilators may be used with an inhaler or taken in tablet form. Reducing exposure is essential.

15. Asbestos exposure
Causes parenchymal fibrosis with > 10 years of moderate exposure
Features
Causes bilateral mid-thoracic pleural thickening/plaque/calcification formation.
Chest X-ray shows diaphragmatic calcification with sparing of the costophrenic angle
Malignant mesotheliomas are associated (80%) with asbestos exposure
Asbestosis results from > 10 years of moderate
exposure. Smoking has a synergistic effect with asbestosis in development of lung CA (adeno and squamous)

16. Asbestosis - Pleural Plaques

17. This long, thin object is an asbestos fiber

18. Silicosis Requires years of exposure to crystalline silica to develop
(as in mining, glassmaking, ceramics, sandblasting, foundries,
and brick yards—with a latency of years.
Acute form: large exposures to fine particles
--- may develop in months, not years
Hallmark of chronic forms:=nodules
- simple: small nodule <1 cm, usually upper lung zones
- not associated with symptoms or pulmonary function
changes
- complicated: leads to progressive massive fibrosis
nodules > 1 cm

19. Silicosis showing calcified coalescence areas in upper lobes
broncholiths 2 mm in diameter
showing calcified coalescence
areas in upper lobes

20. Berylliosis Caused by a cell-mediated immune response that can
occur from > 2 years exposure to even slight amount of beryllium. Suspect in people working in high-tech electronics, alloys, ceramics, and pre-1950 fluorescent light manufacturing.
Affects upper lobes (like silicosis, TB)
Have hilar lymphadenopathy that looks identical to that caused by sarcoidosis on chest X-ray.
Diagnose by beryllium lymphocyte transformation test.
Treat with corticosteroids.

21. Non-Occupational ILD Idiopathic pulmonary fibrosis (IPF)
BOOP (bronchiolitis obliterans organizing pneumonia)
Collagen-vascular diseases
Sarcoidosis
Eosinophilic Granuloma
Lymphangioleiomyomatosis
(pronounced lim-fan-g-o-lie-o-my-o-ma-toe-sis)
Vasculitis causing ILD: Churg-Strauss
Goodpasture syndrome
Eosinophilic pneumonia

22. Idiopathic Pulmonary Fibrosis
Etiology uncertain (autoimmune?) It is a diagnosis of exclusion
Accounts for 50% of ILD’s
No extrapulmonary manifestation of the disease
Male = female, average age = 55
Smoking worsen disease
10% may have low titers of ANA or RF

23. IPF presentation
Dyspnea and cough and diffuse infiltrative process on CXR
Clubbing is common
History of progressive exercise intolerance
Dry crackles at lung bases
Like many ILD’s, PFT’s show a “restrictive” pattern (low TLC, normal FEV1/FVC, low DLCO)
Diagnosis:
confirmed in about 25% of patients by transbronchial biopsy. If transbronchial biopsy is not sufficient, a thorascopic-guided lung biopsy or open lung biopsy should be done-especially when there is any suggestion that there may be an infection involved or in younger patients.
Treatment: corticosteroids + or – cyclophosphamide or azathioprine (20-30% of patients show improvement. This disease progresses to death. Single-lung transplantation is an option for some late-IPF patients. Pneumococcal and influenza vaccines should be given.

24. Sarcoidosis
A disease characterized by the presence of granulomatous tissue.
This is a systemic disease which involves eyes, brain, heart, lungs, bones and kidneys, skin, liver and spleen.
On pathology a non-caseating granuloma composed of histiocytes, giant cells and lymphocytes.
In advanced lung disease fibrotic changes are seen.

25. Etiology Unknown, likely immunological basis. Clinical Features
Four stages are identified:
Stage 0: No obvious intrathoracic involvement
Stage 1: Bilateral hilar lymphadenopathy, often accompanied by arthritis, uveitis and erythema nodosum.
Stage 2: Pulmonary parenchyma is also involved, changes in mid and upper zones.
Stage 3: Pulmonary infiltrates and fibrosis without adenopathy.

26. Stage I (bilateral hilar adenopathy)

27. Stage II Reticular nodules and BHL

28. Treatment and Prognosis
Pulmonary Function
No impairment occurs in stages 0 and 1.
In stages 2 and 3 restrictive changes are seen.
Treatment and Prognosis
85% of these patients improve spontaneously, but 15% may develop progressive fibrosis and respiratory failure.
Prednisone mg/kg initially, then tapered and continued for 6 months to 1 year.

29. Mental Break

30. Hypersensitivity Pneumonitis
Also known as extrinsic allergic alveolitis.
Hypersensitivity reaction in the lung occurs in response to inhaled organic dust.
Example is farmer’s lung.
The exposure may be occupational or environmental.
The disease occurs from type III and type IV hypersensitivity reactions.
Farmer’s lung is due to thermophilic actinomyces in moldy hay.
Bird fancier’s lung is caused by avian antigen.

31. Pathology
There is infiltration of alveolar walls with lymphocytes, plasma cells and histiocytes.
There are loosely formed granulomas.
Fibrotic changes occur in advanced disease.

32. Clinical Features Acute Hypersensitivity Pneumonitis
The disease may occur in acute or chronic forms.
Acute Hypersensitivity Pneumonitis
Dyspnea, fever, malaise and cough appear 4-6 hours after exposure.
These symptoms continue for hours.
Physical examination shows fine crackles throughout the lungs.
These patients present with progressive dyspnea over a period of years.
Chest radiograph may be normal, but may show reticular nodular infiltration.

33. Chronic Hypersensitivity Pneumonitis
These patients present with progressive dyspnea.
Physical examination shows bilateral inspiratory crackles.
Chest x-ray shows reticular nodular infiltration and fibrosis predominantly in upper lobes.
Pulmonary function tests – restrictive pattern.
Gas exchange shows hypoxemia which worsens on exercise.

34. Interstitial Disease Caused by Drugs, Poisons and Radiation
Various drugs cause acute pulmonary reaction – proceeding to interstitial fibrosis.
These drugs are busulfan, nitrofurantoin, amiodarone, bleomycin.
High oxygen concentration – interstitial fibrosis.
Radiation exposure – acute pneumonitis – fibrosis.

35. Bronchiolitis Obliterans Organizing Pneumonia (BOOP)
BOOP is bronchiolitis (inflammation of the small airways) and a chronic alveolitis (the organizing pneumonia). In adults, it is associated with penicillamine use.
Common presentation is an insidious onset (seeks to 1-2 months), of cough, fever, dyspnea, malaise, and myalgias. Multiple courses of antibiotics without effect. Rales are common. Chest X-ray shows some interstiial disease, bronchia thickening, and patchy bilateral alveolar infiltrate.
It has good prognosis and responds to steroids.
Open lug biopsy is the definitive means of diagnosing BOOP.

36. Eosinophilic granuloma
Previously called “Histiocystosis X”
Smokers; and M > F
It sometimes involves the posterior pituitary-leading to diabetes insipidus
In the lung, it causes interstitial changes and small cystic spaces in the upper lung fields, both of which are visible on chest X-ray giving a “honeycomb appearance”.
10 % initialy present with a pneumothorax and up to 50% get a pneumothrorax some time in the course of the illness.
Diagnosis is made by finding Langerans cells on lung biopsy or bronchoalveolar lavage.
Treatment: stop smoking!

37. Vasculitis which causes ILD
Wegener Granulomatosis
- “necrotizing granuloma” which:
1. Affects the upper respiratory tract and paranasal sinuses
2. Causes a granulomatous pulmonary vasculitis with large (sometimes cavitary) nodules
3. Causes a necrotizing glomerulonephritis
Test: ANCA test (90% sensitive and 90% specific); when positive, it virtually always c-ANCA
Diagnosis: confirmed from either a biopsy of the nasal membrane or an open lung biopsy
Treatment: cyclophosphamide with or without corticosteroids.

38. Wegener's Granulomatosis
chest x–ray showing bilateral lung nodules
CT scan from the same patient

39. Wegener’s granulomatosis affecting other sites in the body
Nasal crusting and frequent nosebleeds can occur.
Erosion and perforation of the nasal septum.
The bridge of the nose can collapse resulting in a “saddle–nose deformity”.
This resulted from the collapse of the nasal septum caused by cartilage inflammation
Narrowing of the “windpipe” just below the vocal cords,
a condition called “subglottic stenosis”.
This narrowing, caused by inflammation and scarring

40. Churg-Strauss
necrotizing small vessel vasculitis with eosinophilic infiltration.”
it may affect the skin and kidney, and may cause neuropathy
Patients usually presents with preexisting asthma and have
eosinophilia (up to 80% of the WBCs!)
-Consider this with a progressively worsening asthmatic
-Treatment: Aggressive therapy with cytotoxic agents and
corticosteroids.

41. Other ILD’s Goodpasture Syndrome
- Autoimmune; young adult males M to F is 3 : 1
- hemoptysis that usually precedes renal abnormalities
- May have Fe anemia
- Symptoms due to anti-glomerular basement memberrane antibodies which result in linear deposition of IgG and C3 on alveolar and glomerular BM.
- Treat with immunosuppressives and plasmapheresis

42. Idiopathic Pulmonary Hemosiderosis
causes intermittent pulmonary hemorrhage
It is similar to Goodpasture except IPH does not affect the kidneys
Fe deficiency anemia occurs
It may remit in young patients, but it is unrelenting in adults.

43. The End