INTERSTITIAL LUNG DISEASES

Interstitial lung diseases (ILD) also referred as diffuse lung diseases (DLD), include a large group of uncommon, heterogeneous, familial or sporadic diseases of lung interstitium and distal air spaces that cause significant impairment of gas exchange.

Etiology of ILDs is extremely heterogeneous. While developmental or genetic disorders of surfactant dysfunction are more important in infants, post- infectious, environmental or systemic causes dominate in older children (Table 16.26).

Pathophysiology varies with the cause, with common feature of the remodeling of the distal airspaces, leading to impaired gas exchange. Earlier thought to be a sequel of persistent underlying inflammation, current paradigm has shifted from inflammation to the tissue injury with aberrant wound healing and collagenous fibrosis. Fibrotic remodelling of airways and alveoli leads to persistent hypoxemia that in turn results in vascular remodeling and pulmonary hypertension, i.e. cor pulmonale.

Clinical presentation varies with the cause, though most cases present with insidious onset of persistent (not episodic) respiratory distress which may gradually lead to persistent hypoxia, hypercarbia and failure to thrive. Chest examination is surprisingly near-normal despite the dyspnea. Appearance of persistent cyanosis with loud P₂ suggests development of cor pulmonale.

Diagnosis of ILD must be considered in after exclusion of common causes in cases with at least 3 of the following 4 criteria:

a. Persistent or progressive respiratory symptoms, e.g. cough, dyspnea and exercise intolerance;

b. Persistent or progressive respiratory signs, e.g. tachypnea, adventitious sounds, retractions, clubbing, failure to thrive or respiratory failure;

c.

d. Diffuse abnormalities on a chest X-ray or CT scan (Fig. 16.14).

Detailed history may help to identify the underlying cause, e.g. positive family history (surfactant dysfunction), exposure to molds/birds (hypersensitivity pneumonitis),

TABLE 16.26: Interstitial lung diseases in infants and young children (American Thoracic Society 2013)

Disorders most prevalent in infancy

• Diffuse developmental disorders:

- Acinar dysplasia,

- Congenital alveolar dysplasia

- Alveolar capillary dysplasia

• Growth abnormalities with deficient alveolarization:

- Pulmonary hypoplasia

- Bronchopulmonary dysplasia

- Chromosomal disorders, e.g. Down syndrome

- Congenital heart disease

• SpeciRc conditions of undefined etiology:

- Neuroendocrine cell hyperplasia of infancy

- Pulmonary interstitial glycogenosis

• Surfactant dysfunction disorders:

- Pulmonary alveolar proteinosis (PAP)

- Desquamative interstitial pneumonia (DIP)

- Non-specific interstitial pneumonia (NsIP)

- Chronic pneumonitis of infancy (CIP)

Disorders not-specific to infancy

• Disorders of normal host:

- Post-infectious: Adenovirus, Infiuenza, mycoplasma

- Environmental: Hypersensitivity pneumonitis, toxic inhalation

- Others: Recurrent aspiration, eosinophlic pneumonia

• Disorders related to systemic diseases:

- Immunological: SLE, Good-Pasture syndrome

- Storage disorders: Gaucher disease

- Hematological: Histiocytosis

- Others: Sarcoidosis, hemosiderosis

• Disorders related to ImmunodeRciency states:

- Lymphocytic Interstitial Pneumonitis (LIP) in HIV

- Granulomatous lymphocytic ILD of CVID

- Opportunistic infections: Chemotherapy, radiation, transplant

• Disorders masquerading as ILD:

- Pulmonary vasculopathies

- Pulmonary lymphatic disorders

- Congestive lung due to cardiac dysfunction

- Unclassified

hemoptysis (pulmonary hemosiderosis), rash or arthritis (connective tissue disease)

Chest X-rays may be normal in ILD despite severe clinical disease or may show interstitial, reticular, nodular, or honeycombed lesions (Fig. 16.14).

Pulmonaryfunction tests are useful to assess the severity of pulmonary dysfunction and response to treatment. Most cases reveal restrictive lung disease with decreased lung volumes and compliance. Diffusion capacity of the lung is often reduced. Exercise testing may detect pulmonary dysfunction even in the early stage of ILD with a decline in oxygen saturation.

Fig. 16.14: Interstitial lung disease.

Bronchoalveolar lavage may be useful to detect secon­dary infection, bleeding and aspiration, as well as to collect samples for cytology and molecular analyses.

Lung biopsy is often necessary for diagnosis. Genetic testing for surfactant dysfunction mutational analysis is indicated in infants and toddlers with ILD.

Management revolves around supportive care with supplemental oxygen for hypoxia, adequate nutrition for growth failure and antimicrobials for secondary infections. Some children may benefit symptomatically with bronchodilators.

Immunosuppressive therapy with systemic corticosteroids for 6-8 weeks is the treatment of choice in most cases of chILD, though controlled trials are lacking. Alternatives include other immunomodulators, e.g. hydroxychloroquine, azathioprine, cyclophosphamide, cyclosporine, methotrexate, intravenous immunoglobulin, etc. Investigational approaches involve specific agents directed against the action of cytokines, growth factors, or oxidants. Lung transplant for progressive or end-stage ILD has been successful in some cases.

Specific treatment is available for some DLDs including antimicrobials for certain infections, management of swallowing dysfunction and/or GERD in patients with chronic aspiration, avoidance of the offending antigen in hypersensitivity pneumonitis, and whole lung lavage for older children with pulmonary alveolar proteinosis.

Outcome of chILD is variable. Some children recover spontaneously without treatment, but others may progress to death. Reported 5-year mortality rates vary from ~30-50%. Pulmonary hypertension, failure to thrive, and severe fibrosis are considered as poor prognostic indicators.

Prevention includes avoidance of inhalation irritants, immunization for respiratory infections and genetic counseling in cases of positive familial history.

16.10.5