The Interstitial Lung Diseases - Rare Entity

Introduction

ILDs consist of distinct entities with known and unknown aetiologies and a wide range of clinical manifestations, radiological and pathological patterns, and outcomes. The word "interstitial lung disease" refers to various lung disorders. The interstitium, a component of the lungs, is the target of all disorders classified as interstitial lung diseases. It supports the alveoli, the minute air sacs found in the lungs. X-rays and CT scans typically do not reveal the presence of the interstitium because of its fragile nature.

What Are the Different Conditions?

Surfactant (a combination of fatty acids and proteins that are produced in the lungs) accumulates in the alveoli as a consequence of faulty clearance by alveolar macrophages (a specific kind of white blood cell that surrounds and destroys germs, eliminates dead cells, and promotes other cells of the immune system to function.), leading to varying degrees of respiratory insufficiency.

• Autoimmune PAP: A rare condition known as autoimmune pulmonary alveolar proteinosis (PAP) is characterized by dysfunction in myeloid cells (myeloid cells are blood cells that develop in the cartilage of the marrow. As a myeloid cell evolves into an adult blood cell, it becomes a basophil, eosinophil, erythrocyte, macrophage, monocyte, neutrophil, or platelet), aberrant buildup of pulmonary surfactant, and a weakness in the innate immune system. Typically, the disease manifests with exertional dyspnea (the sense of running out of air and being unable to breathe quickly or deeply enough) during physical exercise. However, most patients exhibit no symptoms. Other prevalent symptoms include cough, fatigue, weight loss, and chest pain or hemoptysis (blood-spitting wheezing), which typically indicate complications.

• PAP Secondary: The majority of secondary PAP is caused by hematological disorders, particularly myelodysplastic syndromes (a type of malignancies that occur when immature blood cells of the bone marrow cannot transform into healthy blood cells or mature as they should) and acute myeloid leukemia (Acute myelogenous leukemia (AML) is a malignancy of the blood and bone marrow, where blood cells are produced). PAP is uncommon in immunodeficiency. Even though acute leukemia can be cured by haematologic therapy, chemotherapy, and bone marrow transplantation alone, the underlying disease must be treated. The effect of WLL (the conventional treatment method is called whole lung lavage (WLL), which involves physically removing the proteinaceous material from the afflicted lung) on secondary PAP is short-lived.

• Genetic PAP: Genetic PAP affects children and has a dismal prognosis. Mutations mostly affect surfactant-producing genes. Genetic PAP resembles autoimmune PAP but has different radiology and histology. Lung cysts and diffuse ground-glass opacities are typical. Mutations influence macrophages (a white blood cell that surrounds and destroys germs eliminates dead cells, and promotes cells from the immune system to function.) and surfactant degradation. The disorders resemble autoimmune PAP (Myeloid cell malfunction, aberrant pulmonary surfactant buildup, and innate immune insufficiency characterize this unusual disorder). Corticosteroids are favored and can be coupled with immunomodulators. Lung transplantation is necessary in advanced situations. GM-CSF receptor genetic abnormalities cause autoimmune PAP-like illnesses in children.

• PPFE: Primary Pulmonary Fibrosis with Emphysema (PPFE) represents a relatively uncommon display of interstitial pneumonia. The condition is distinguished by fibrosis in the upper lobe and subpleural region, affecting both the visceral pleura and the underlying subpleural lung tissue (pulmonary opacities that do not involve the lung periphery and are often located one centimeter or less from the pleural surface). This fibrosis is characterized by significant elastosis(an extremely uncommon skin illness characterized by the transepidermal removal of aberrant elastic fibers.) of the alveolar walls and thickening of the visceral pleura with fibrous tissue.

• Dyskeratosis Congenita and Telomerase-Associated Pulmonary Fibrosis: Dyskeratosis congenita is a condition that can have an impact on a wide variety of bodily systems. This condition is distinguished by three distinct symptoms: fingernails and toenails that do not grow properly or have an abnormal shape (nail dystrophy); changes in the skin's pigmentation, particularly on the chest and neck, in a pattern that is frequently referred to as "lacy"; and white patches within the mouth (oral leukoplakia).

Telomere abnormalities (a variety of genetic illnesses known as telomere biology disorders (TBDs) are brought on by pathogenic and likely pathogenic uncommon germline mutations in the genes that encode crucial elements for telomere maintenance.) have been associated with X-linked, autosomal dominant, and autosomal recessive diseases. Due to the prevalence of de novo mutations (A term used to define an alteration in the DNA sequence for a gene that is first observed in an individual and has not been observed in previous generations.) in the X-linked and dominant genes, DC frequently occurs in sporadic instances. Parents of afflicted children who are asymptomatic run the risk of carrying harmful alleles. These conditions exhibit a range of clinical manifestations, including cutaneous abnormalities, premature hair graying, bone marrow failure, liver disease, and pulmonary complications. Among these, pulmonary fibrosis is the prevailing pulmonary manifestation.

What Are the Causes and Risks?

The majority of interstitial lung diseases have unknown causes. Bacteria, viruses, and fungi cause interstitial pneumonia. It can also develop ILD if irritants to the lungs are frequently inhaled. These consist of:

• Asbestos bird proteins (including those derived from exotic birds, poultry, and pigeons).

• Coal dust and other metal dust from mining operations.

• Grain particles from agriculture.

• Silica particles.

• Talc.

Rarely, but certain medications can cause ILD:

• Certain antibiotics, including Nitrofurantoin.

• Some anti-inflammatory medications, such as Rituximab.

• Chemotherapy medicines such as Bleomycin.

• Medications for the heart, such as Amiodarone.

Anyone can develop interstitial lung disease, but certain factors increase the risk:

• ILD is much more prevalent in adults, but minors can also be affected.

• Autoimmune diseases.

• Genetics of gastroesophageal reflux disease (GERD). Some conditions are transmitted within families.

• Smoking.

• Treatments with radiation for cancer.

What Are the Treatment Methods?

The nature of the treatment administered is contingent upon the specific classification of interstitial lung disease (ILD) and its underlying etiology.

• Antibiotics: These medications are effective in treating the majority of interstitial pneumonia. Pneumonia resulting from viral cause typically exhibits a self-resolving nature. Fungal-induced pneumonia is an infrequent occurrence, they are managed through the administration of antifungal medications.

• Corticosteroids: Certain types of interstitial lung disease involve inflammation within the lungs, leading to consequential damage and scar tissue formation. Corticosteroids induce a deceleration in the activity of the immune system. This reduces inflammation in both the pulmonary system and the overall physiological state.

• The Act of Inhaling Oxygen: In cases of interstitial lung disease, the administration of inhaled oxygen has been found to alleviate symptoms associated with low oxygen levels. Frequent utilization of oxygen may confer cardioprotective benefits by mitigating the detrimental effects of hypoxia on the heart.

Individuals with advanced interstitial lung disease that has resulted in significant impairment may require a lung transplantation procedure. A significant improvement in both quality of life and exercise capacity is commonly observed among individuals who undergo lung transplantation as a treatment for interstitial lung disease.

• Azathioprine: It is a medication commonly used in clinical settings, this medication exhibits immunosuppressive properties.

N-acetylcysteine, is a pharmaceutical compound. In certain manifestations of interstitial lung disease, the deceleration of lung function deterioration may be observed with the administration of this powerful antioxidant. The medication will be administered concurrently with other therapeutic interventions. There are several drugs that are deemed controversial in the realm of interstitial lung disease treatment, which include:

• Other Medication: The medications Cyclophosphamide, Cyclosporine, Methotrexate, Nintedanib, and Pirfenidone are commonly used in the treatment of various medical conditions. These medications have an impact on the functioning of the immune system. If a medical professional determines that a patient requires medication, they will closely monitor the patient during treatment. These pharmaceutical drugs may induce severe adverse reactions.

What Are the Complications?

There is a risk of death associated with the complications of severe interstitial lung disease, which include the following:

• Pulmonary hypertension (high blood pressure) that occurs in the lungs.

• Failure of the respiratory system.

• Insufficiency of the right side of the heart, also known as cor pulmonale.

Conclusion

Numerous uncommon and ultra-rare ILDs are probably misdiagnosed. Increased understanding of their pathobiology, genetics, and disease behavior has led to the development of more effective treatment options, including highly effective targeted therapies for some diseases, while in others, transplantation or palliative care may be the only remaining option. To diagnose, optimally treat, and support patients with rare ILDs and advance the field, it is recommended to consult with or refer patients to specialized centers as soon as possible.