Interstitial and Infiltrative Lung Diseases

Interstitial lung disease is a heterogeneous group of inflammatory and fibrotic disorders of lower respiratory tract that involves the lung interstitum.   These disease are classified together because they share many characteristics even though it is a broad group.

Interstitial space is the continuum of loose connective tissue through out the lung.  It is made of 3 subdivisions.

1.      bronchoarterial- surrounds the bronchoarterial bundles

2.      parenchmyal- between alveolar and capillary basement membrane

3.      subpleural- between the pleura and parenchyma and continuous with the interlobar septa

Infiltrate- is any substance or type of cell that occurs within or spreads throughout the interstitium and/or the alveoli of lung.  It is foreign to the lung or accumulates in greater than normal quantity within it.

Case 1: 

A 23 year old woman was admitted to the hospital because of increasing fatigue and shortness of breath of 2 months duration (subacute ) Her symptoms of fatigue, dyspnea started insidiously 2 months prior to admission and had gradually worsened.  6 weeks prior to admission she developed arthralgias and a week later, she noted the onset of a dry, irritative cough.  Soon after she had low-grade fevers occurring several days of each week.  Physical exam- showed tachypneic at rest, BP 110/70, pulse 114, RR 24/min. Temp 99.1 F.  Patient became dyspneic with walking across exam room and appeared cyanotic. Findings are bilateral crackles in both lung bases. Heart had regular rhythm. No murmurs or abnormal heart sounds were present. The pulmonic component of the second heart sound was increased intensity.
 

Case 2:

55 year old woman who noted gradual onset of excertional dyspnea and a dry cough without obvious cause over several year period.  A detailed work and environmental history revealed no evidence of significant occupational exposure.  Physical exam reveal dry inspiratory crackles most prominent at the lung bases. 

On history: dyspnea and cough , systemic symptoms can vary (like fever, weight loss, arthralgia)

On physical exam: crackles at the base of the lungs 

On lab findings:  

ABGs on RA (arterial blood gasses on room air): hypoxemia, with widened [A-a]O2 gradient.

PFTs (pulmonary function test) : restrictive ventilatory pattern

CXR (chest x-ray) :  bilateral diffuse infiltrates
 

Clinical Classifications of interstitial lung disease

1. Connective tissue disease- (generally systemic and involve many organs, but at lungs you will see interstitial changes )
   1. Scleroderma
   2. Polymyositis
   3. SLE
   4. RA- rheumatoid arthritis
2. Treatment or drug-induced
   1. Antibiotics-
   2. Anti arrythmics- quinidine
   3. Anti-inflammatory-
   4. Anti-convulsants- dilantin
   5. Chemotherapy- methotrexate, gleomycin
   6. Therapeutic radiation
   7. High levels of O2
   8. Paraquat = insecticide
3. Primary (unclassified) disease
   1. Sarcoidosis- more on this following
   2. Eosinphilic granuloma
   3. Amyloidosis
   4. Lymphangitic carcinomatosis
   5. ARDS  (acute respiratory distress syndrome)
4. occupation and environmental
   1. inorganic

·        silicosis

·        asbestosis

·        berylliosis

·        siderosis

·        stanosis

2. organic (hypersensitivity pneumonitis)

·        bird breeder’s lung – from bird droppings

·        farmer’s lung-

5. iditopathic fibrotic disorders
   1. idiopathic pulmonary fibrosis
   2. bronchioloits obliterans
   3. organizing pneumonia

The 2 disease that he did talk about are Sarcoidosis and Idiopathic pulmonary fibrosis

1.  Sarcoidosis = Case 1

-         it is a chronic multi-system disorder of unknown cause

-         Characterized by accumulation of T cells and mononuclear phagocytes

-         Have a specific inflammatory pattern found on biopsy

-         Noncaseating epithelioid granulomas and derangements of the normal tissue architecture

-         Clinically- has to involved multiple  organs, which are commonly the lungs, liver, spleen, skin, eyes, phalangeal bones, heart, and parotid gland

-         Delayed hypersensitivity is depressed

-         It is a disease of exclusion. If you can find a cause of the granuloma, such as TB, beryllium, fungi, than it’s not sarcoidosis, but if you can’t find another cause than it is sarcoidosis

-         Onset- Ages 20-40 years and will see systemic symptoms  like fever, fatigue, and weight loss
 

Staged by chest x-ray

Stage 1 = enlarged hilar lymph nodes

Stage 2 = enlarged hilar lymph nodes + infiltrates in lung

Stage 3= interstitial infiltrates alone

Stage 4 = end stage fibrosis
 

Symptoms are those of interstitial lung disease

1. Dyspnea, cough, wheezing
2. Organ involvement symptoms depending on where the granulomas are located
   1. skin, eye , joints, Nervous system, cardiac, GI, bone marrow,  
   2. less commonly kidney and endocrine systems

2. Idiopathic pulmonary fibrosis (aka cryptogenic fibrosing alveolitis) = case 2

-         rare, prevalence (3.5/100,000)

-         commonly in older people (50-70 years old)

-         insidious onset (gradual progression w/ unapparent symptoms) of dyspnea and cough

-         systemic symptoms are less common,

-         clinical findings described are common with other interstitial lung diseases (ILD)

To diagnose an ILD, need to have suspicion based on clinical findings and afterwards you need tissue sample findings (infiltrates) from a biopsy for diagnosis. This is done by either a transbronchial biopsy (a bronchoscope is placed through your nose/mouth and small forceps are passed through it to obtain samples) or an open lung biopsy.
 

Treatments:

Prednisone (steroids) as an immunosuppressant is used for sarcoidosis, but it can change the systemic response because steroids can suppress them. However, it is not clear what the long term outcome will be of using steroids. Most can resolve spontaneously without drugs.  With idiopathic pulmonary fibrosis steroids are commonly used in treatment, but they are not really effective.  
 

Both diseases are well distributed among male and females.  There may be a slight female preponderance, but it is not significant. 
 

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