Interstitial lung disease

Last updated date: 09-Jun-2023

Originally Written in English

Interstitial lung disease

Interstitial Lung Disease


Interstitial lung disease (ILD) refers to a group of disorders that induce scarring (fibrosis) of the lungs. Scarring stiffens the lungs, making it difficult to breathe and get oxygen into the circulation. ILD-caused lung damage is frequently permanent and worsens over time.


Interstitial lung disease definition

Interstitial lung disease definition

Interstitial lung disease (ILD), also known as dispersed parenchymal diseases, refers to a group of different lung ailments that are grouped based on clinical, radiological, physiologic, or pathologic features in common. The convoluted language is what makes this category of disorders difficult to grasp.

In reality, the pathogenetic sequence consists of a succession of inflammation and fibrosis that extends beyond altering the interstitial bed (as the name indicates) to affecting the parenchyma (alveoli, alveolar ducts, and bronchioles). The causes of infiltrative illnesses are numerous. Many of them are quite uncommon. Because the pattern of illness dissemination differs amongst populations, making an accurate diagnosis is critical.

Thorough patient history and physical examination provide invaluable information that can be combined with appropriate laboratory testing, imaging, and, if necessary, tissue biopsy to reach a confident ILD diagnosis, and high-resolution computed tomography (HRCT) of the thorax is usually an important component of the diagnostic evaluation. Many types of ILD can react dramatically to immunosuppressive anti-inflammatory medications if therapy is recommended.

However, ILD coupled with severe fibrosis may be difficult to treat, and despite the completion of several phase 3 clinical studies over the last decade, the finding of a viable pharmacologic treatment for idiopathic pulmonary fibrosis (IPF) has remained elusive. Nonetheless, patients with IPF or advanced forms of non-IPF ILD can benefit significantly from early detection and treatment of various co-morbid conditions that are common in patients (especially the elderly), and supportive care (oxygen therapy, pulmonary rehabilitation) can improve quality of life and symptom relief.

Finally, lung transplantation is a possibility for patients with progressive, severe illness that has not responded to previous therapy; however, only a tiny proportion of individuals with end-stage ILD complete wait list conditions and finally receive successful lung transplantation. 



It has been challenging to ascertain the incidence rates of interstitial lung disease in the United States. Many people believe that the prevalence is significantly more than previously reported. The claimed prevalence might be so low due to a failure to detect the condition. ILD is an exclusionary diagnosis that necessitates further research.

It is now easier to revised guidelines/classifications. The annual incidence is expected to be 30 per 100,000 people. Males have an overall prevalence of 80.9 per 100000 per year, while females have a prevalence of 67.2 per 100000 per year. These figures come from one of the most significant epidemiologic investigations, which was conducted in Bernalillo County, New Mexico.



The interstitial lung disease categorization system categorizes illnesses based on clinical, histological, or radiologic features. ILD is classified clinically based on its etiology in order to distinguish between exogenous and endogenous components. Interstitial lung disease illnesses with no known etiology are classified as idiopathic/primary, with the histopathological and radiographic approaches serving as the infrastructure.


Known causes

  • Environmental and occupational exposure

Long-term occupational or environmental exposure can have a harmful effect on the lungs. Mineral dust, organic dust, and poisonous gases are all common agents. Many various forms of mineral dust have been linked to the condition, but the most commonly mentioned are silica, asbestos, coal mine dust, beryllium, and hard metal.

Mold spores and aerosolized bird droppings are examples of organic dust. Toxic gases (methane, cyanide) inhaled cause direct harm to the airways or cause reactive oxygen molecules to form. The amount of exposure-related damage is difficult to quantify epidemiologically. It is likely to occur more frequently than previously believed. That is why meticulously reviewing a patient's whole job history and residence to seek any indication of probable agent-disease links is crucial.


Auto-Immune diseases

Interstitial lung illness is a typical aspect of rheumatic disorders because connective tissue diseases and vasculitides impact all parts of the lungs 


Drug-induced ILD:

More than 350 medications have been linked to pulmonary problems, either as reactive metabolites or as part of a broader reaction. With adequate clinical data, a diagnosis is achievable and, in most situations, should be made after alternative reasons have been ruled out. Although radiological results are variable, since medication responses typically influence the parenchyma, an interstitial pattern is most commonly detected. Histopathology varies as well. Eosinophilic pneumonia or hypersensitivity pneumonitis are the most prevalent patterns found.


Idiopathic disease

This is the most frequent variation. In contrast to infectious pneumonia, this primary group is known as idiopathic interstitial pneumonia, which is characterized by inflammation and fibrosis. There are seven main kinds, distinguished by histological characteristics and clinical differences. The majority of instances are sporadic, however, genetics may play a role. 



Interstitial Lung Disease Pathophysiology

Many of the disease's subtypes have an unclear cause. Regardless, they all eventually evolve in the same way. Histologically, the morphological alterations visible originate from a series of inflammations inside the parenchyma, which is the region of the lung engaged in gas exchange.

This compartment is home to a variety of proteins and pro-fibrotic components. After repeated activation cycles, these proteins cause connective tissue to accumulate. The trigger might be a recognized chemical that has been deposited in the lung tissues. In certain circumstances, fibrosis develops on its own.



Interstitial Lung Disease Symptoms

The most commonly reported symptom is a slow development of dyspnea, however it can also be a cough. An unremitting cough, for example, is the most common presenting symptom in individuals with bronchiolitis obliterans organizing pneumonia. Pleuritic chest discomfort is uncommon in general, although it does occur in some subtypes, such as sarcoidosis. Hemoptysis can occur as a result of diffuse alveolar hemorrhages. A patient, on the other hand, maybe perfectly asymptomatic but have aberrant imaging.

Details on any environmental or occupational exposures, current and prior medication lists, a history of any radiation exposures, fumes, dust, or toxic inhalation should all be included in the history. The importance of family history cannot be overstated, as genetics can play a role. Rheumatologic disease symptoms should be examined, however, keep in mind that dyspnea may be the only presenting symptom of rheumatological-associated interstitial lung disease.

Bibasilar crackles on physical examination are distinctive but not always a consistent observation. Patients with severe illness may experience digital clubbing or physical symptoms of pulmonary hypertension, such as an increase in the intensity of the P2 of the second heart sound.



Interstitial Lung Disease Diagnosis

It might be difficult to determine the source and severity of interstitial lung disease. A physician may be able to obtain a diagnosis with a complete history and supportive laboratory tests, but a greater diagnostic yield may necessitate the involvement of an interprofessional team. Interstitial lung disease encompasses a wide range of illnesses with varying therapy approaches and prognoses, which is why determining a definitive diagnosis is critical. It begins with thorough patient history and physical examination, followed by laboratory tests, imaging, physiologic testing, and sometimes a biopsy.

The initial normal laboratory assessment consists of a complete blood count to look for signs of hemolytic anemia, as found in SLE, or eosinophilia, as seen in drug-induced SLE. Hepatic function, renal function, and serologic tests should all be included in laboratory testing. In some circumstances, infectious research may be necessary (HIV, hepatitis).

The imaging process begins with a standard chest radiograph. A reticular pattern is the most typical radiographic characteristic detected, however nodular or mixed patterns can also be seen. Some of these patterns might occasionally help you limit your options. An X-ray showing mediastinal lymphadenopathy may indicate the existence of lymphoma or sarcoidosis. In the instance of a negative CXR, high-resolution computed tomography (HRCT) can provide a better depiction of the illness and potentially help in diagnosis; the HRCT must be performed supine.

In certain circumstances, it may have a conventional radiological pattern of a disease, such as typical interstitial pneumonia (UIP). Subpleural and basilar predominant alterations, reticular patterns, honeycomb changes with or without traction bronchiectasis are the characteristic radiological features of UIP on HRCT. If the diagnosis is still uncertain after taking into account the history, test data, and radiographic findings, an invasive workup may be necessary. Bronchoalveolar lavage (BAL) results are generic, which means there are no abnormalities in a BAL that are pathognomonic for a specific form of ILD.

BAL, on the other hand, can be useful in limiting down the alternatives. BAL, for example, will indicate significant lymphocytosis in individuals suspected of having hypersensitivity pneumonitis. The choice to have a lung biopsy should be made on an individual basis. A lung biopsy is not required in every situation. It is especially useful in the diagnosis of sarcoidosis and idiopathic interstitial pneumonia.

Complete lung functions and oxymetry are required for all patients with ILD for prognosis and disease monitoring. 



Interstitial Lung Disease X-rays

Although chest radiography is frequently the first test used to diagnose interstitial lung disorders, it can be normal in up to 10% of patients, especially early in the illness phase.

The recommended modality is high-resolution CT of the chest, which varies from regular CT of the chest. As a result, the HRCT has about ten times the resolution of a normal CT chest, allowing the HRCT to reveal minutiae that would otherwise be invisible.

However, radiologic appearance alone is insufficient and should be evaluated in the clinical context, bearing the temporal profile of the illness process in mind.


Interstitial lung diseases can be classified according to radiologic patterns. 

Pattern of opacities


Acute: Alveolar hemorrhage syndromes, acute eosinophilic pneumonia, acute interstitial pneumonia, cryptogenic organizing pneumonia

Chronic: Chronic eosinophilic pneumonia, cryptogenic organizing pneumonia, lymphoproliferative disorders, pulmonary alveolar proteinosis, sarcoidosis



  • Upper lung predominance

Pulmonary Langerhans cell histiocytosis, silicosis, coal workers pneumoconiosis, carmustine related pulmonary fibrosis, respiratory broncholitis associated with interstitial lung disease.

  • Lower lung predominance

Idiopathic pulmonary fibrosis, pulmonary fibrosis associated with connective tissue diseases, asbestosis, chronic aspiration

  • Central predominance (perihilar)

Sarcoidosis, berylliosis

  • Peripheral predominance

Idiopathic pulmonary fibrosis, chronic eosinophilic pneumonia, cryptogenic organizing pneumonia


Associated findings

  • Pleural effusion or thickening

Pulmonary edema, connective tissue diseases, asbestosis, lymphangitic carcinomatosis, lymphoma, lymphangioleiomyomatosis, drug-induced lung diseases

  • Lymphadenopathy

Sarcoidosis, silicosis, berylliosis, lymphangitic carcinomatosis, lymphoma, lymphocytic interstitial pneumonia

  • Genetic testing

Genetic reasons have been established for several types of juvenile ILDs and a few types of adult ILDs. Blood tests may be used to detect these. For a small number of patients, there is a distinct benefit since an accurate molecular diagnosis may be made; in many situations, there is no need for a lung biopsy. There is testing available for


Invasive diagnostic procedures

Bronchoscopy and/or surgical lung biopsy may be necessary to make a certain ILD diagnosis. Bronchoscopy is a relatively safe operation when conducted by a skilled bronchoscopist, with the most significant possible risks being pneumothorax or excessive bleeding as a result of a transbronchial biopsy.

Bronchoalveolar lavage (BAL) is a simple procedure, and the recently published ATS Task Force Report on BAL for the diagnosis of ILD suggests using recently obtained HRCT imaging to choose a suitable portion of the lung from which to do BAL from a wedge posture.

When there is a widespread illness, the right middle lobe or lingula of the left upper lobe is likely the best place to undergo lavage, and areas with ground-glass opacification or profuse nodular change are more likely to yield significant diagnostic information.

BAL fluid and sediment can be tested for infection or the presence of malignant cells, in addition to total and differential BAL cell counts, and the physical appearance of newly extracted BAL fluid may give diagnostic information.


A surgical lung biopsy (SLB) taken using video-assisted thoracic surgery (VATS) or open biopsy is likely to yield a good specimen that reveals a histopathologic pattern that can typically be deemed to be unequivocally diagnostic of a specific disease entity (if correctly conducted).

However, while doing an SLB, one must assess the risks and advantages, especially in fragile elderly patients, patients with ventilatory compromise, patients with moderate to severe pulmonary hypertension, or patients with many co-morbidities. In patients with suspected ILD, open lung biopsy has a 30-day death rate of around 4.3 percent, whereas VATS biopsy looks to be safer, with an associated 30-day mortality rate that is slightly lower than open biopsy but not insignificant at roughly 2.1 percent. 



Interstitial Lung Disease Management

Avoidance of irritants is critical for those interstitial lung illnesses with established etiology. Smoking cessation, pulmonary rehabilitation, which can assist improve functioning, and excellent pulmonary hygiene will be general supportive measures. Supplemental oxygen is required for patients who have hypoxemia.

Corticosteroids are preferred when the condition progresses despite the removal of the offending substance. Corticosteroids help patients with bronchiolitis obliterans organizing pneumonia (BOOP) or hypersensitivity pneumonitis (HP) quickly and dramatically. Immunosuppressant treatment is an experimental therapy for instances that do not respond to corticosteroids.

Corticosteroids and immunosuppressive medicines are the cornerstone treatments for idiopathic interstitial pneumonia. These medications work to stop the inflammatory process in the lungs. Currently, nintedanib and pirfenidone are immunosuppressant medications that have been licensed for the treatment of idiopathic pulmonary fibrosis.

Because the lung architecture has not been significantly altered, several investigations have offered indirect evidence that early treatment during the course of the illness may correspond with therapeutic response. There has been no medication to reverse fibrosis once it has begun, however nintedanib can decrease disease development. Transplantation is the only therapy option that can restore patients' physiological function.


Treatment of IPF

The prognosis of IPF is typically poor, with the majority of patients experiencing gradual loss of lung function and perhaps experiencing abrupt exacerbations with accelerated lung function loss, which often results in death. Traditional therapy for IPF patients have included corticosteroids and cytotoxic medicines (e.g., azathioprine, cyclophosphamide). However, in any adequately powered, prospective, randomized, placebo-controlled clinical trial, these medicines have never been proved to have a meaningful advantage.

Furthermore, it was recently found that azathioprine, a medication that has been thought to have effectiveness in the treatment of IPF, was linked with considerable damage when delivered to IPF patients when compared to placebo. When it became clear that the azathioprine/N-acetylcysteine (NAC)/prednisone arm of the NIH-sponsored IPF PANTHER clinical trial had a higher rate of death and other problems than the other study arms of NAC alone or placebo, the azathioprine/NAC/prednisone arm was terminated.

There are no FDA-approved therapy alternatives for IPF patients, and any pharmacologic treatment administered in the United States would be deemed off-label.

Many novel fibrogenesis-targeting medicines have been tested in Phase 3 clinical trials, although some of these treatments (e.g., bosentan, macitentan, ambrisentan, interferons gamma and beta) have not demonstrated benefit despite pre-clinical research or phase 2 clinical trials indicating potential efficacy. Indeed, there can be significant inter-individual diversity in genetic defects that predispose a person to acquire the illness, pathophysiologic aspects of the disease process, and treatment responses.

It should be noted that a subset of patients who may benefit from a promising drug are unlikely to be identified in a prospective, double-blind, randomized phase 3 clinical trial in which these patients are combined with a much larger number of enrolled subjects for whom the drug has little or no effect, and the conclusion may be reached that the drug lacks benefit despite its potential to help a subset of patients.

Nonetheless, recent clinical trial data show that pirfenidone or nintedanib may have a substantial influence on disease progression over placebo, and pirfenidone has been approved and is clinically accessible in Japan, Europe, and Canada. Stem cell treatment, especially the use of mesenchymal stem cells (MSC), has showed promise in pre-clinical studies, and preliminary findings from a phase 1 clinical study utilizing adipose-derived MSC were recently reported.



Interstitial Lung Disease Prognosis

The prognosis of interstitial lung disorders differs depending on the subgroup. Acute eosinophilic pneumonia, cellular interstitial pneumonia, BOOP, lymphocytic interstitial pneumonitis, pulmonary capillaritis, granulomatous interstitial pneumonitis, and ultimately, alveolar proteinosis are typical treatment responding sub-classes. In any scenario, prognosis is still related to the degree of the disease at the time of presentation. Advanced diseases, such as idiopathic pulmonary fibrosis, are notoriously resistant to treatment.

Complications might include increasing hypoxia, cardiovascular illness, pulmonary hypertension, and infections.



Interstitial lung disease is a complicated condition that necessitates the collaboration of a multidisciplinary team that includes the main physician, nurse practitioner, pulmonologist, thoracic surgeon, pathologist, and radiologist. Asymptomatic individuals may be placed under observation after the diagnosis is determined, but all symptomatic patients require treatment.

Long-term surveillance is required since the illness is known to proceed to fibrosis and end-stage lung disease. It is vital to educate patients on the necessity of quitting smoking. Most patients have a low quality of life, characterized by substantial respiratory difficulty and little physical activity.

To offer optimal patient diagnosis and therapy, an interdisciplinary team that includes the patient's primary care doctor, a pulmonologist, nursing staff, and pharmacists, as well as pulmonary function technologists and respiratory therapists, is ideally suited to handle interstitial lung disease.