Approach to interstitial lung disease (diffuse parenchymal lung disease): Clinical sciences

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Introduction 0:00–0:46

Interstitial lung disease, or ILD, is a group of lung disorders that cause inflammation and scarring of the lung parenchyma.
Based on the underlying cause, ILDs can be subdivided into four main categories: exposure-related ILDs, caused by inhaling harmful substances like asbestos; iatrogenic ILDs, which occur as a result of side effects from certain medications or radiation therapy; ILDs related to systemic diseases, seen in conditions like sarcoidosis; and finally, idiopathic ILDs, where the causes are unknown, like idiopathic pulmonary fibrosis.
Okay let's begin our assessment of a patient presenting with a chief concern suggesting ILD. First obtain a focused history and physical examination, as well as pulmonary function tests, or PFTs, and chest X-ray.

H&P, PFTs, X-rays 0:46–2:28

Patients typically report shortness of breath on exertion, and chronic, dry cough. The physical exam might reveal wheezing, and diffuse inspiratory crackles.
There can also possibly be finger clubbing, cyanosis, and low oxygen saturation. You might also see signs of extrapulmonary systemic disease like polyarthritis or thickened skin, but that will depend on the cause of ILD.
Here’s a clinical pearl! In ILD, patients often present with a normal oxygen saturation when they are at rest, which is about 95-100%, but it drops during physical activity as their body's oxygen demand rises.
So, if a patient initially shows normal oxygen saturation, test for exercise-induced hypoxemia by checking pulse oximetry while they ambulate.
Next, PFTs typically reveal reduced diffusing capacity of the lungs for carbon monoxide and might show a restrictive pattern on spirometry.
Finally, a chest X-ray might reveal diffuse bilateral reticular opacities, which appear net-like in texture,often in the lower and lateral lung zones.
With these findings, consider ILD and order a high-resolution chest CT to confirm your diagnosis. On a chest CT, the main findings typically include reticulations which are thin septal opacities, or ground glass opacities.

Chest CT scan 2:28–3:00

The term Ground glass comes from its similar hazy appearance to glass which has been given a matte finish. In this next radiograph we see a good example of honeycombing, which appears as clusters of enlarged air spaces surrounded by thickened and fibrotic walls.
If you see this, think ILD. Now that we have our diagnosis, let’s talk about possible causes, starting with exposure-related ILDs.

Exposure-related ILD 3:00–6:05

If your patient presents with a history of prolonged exposure to inhaled inorganic material, like asbestos and silica, then immediately suspect pneumoconiosis.
There are various types, depending on the kind of inhaled materials, and even though history taking is key and imaging features often overlap, there are some classic imaging findings that may help the diagnosis.
For example, silicosis can have classic perihilar lymph node calcifications or ‘eggshell calcifications’. Next lets look at Asbestosis, which will typically have calcified pleural plaques.
In both cases, you are dealing with a type of pneumoconiosis. Now, let's consider if your patient has a history of exposure to inhaled organic material, like bird droppings, fungi, or mold.
Additionally, the CT scan shows centrilobular ground glass nodules and air trapping which are abnormal lucent areas. They’re termed air trapping as air is trapped in these lobules, and appears black, or lucent, on x-ray and CT due to its low density.
With these findings you should consider hypersensitivity pneumonitis. Your next step is to obtain a bronchoalveolar lavage, or BAL.
If BAL shows lymphocytosis, diagnose hypersensitivity pneumonitis. Lastly, if your patient has a smoking history, consider smoking-related ILDs.
Now, they might be between 20 and 40 years old and have a history of spontaneous pneumothorax. A chest CT often reveals irregular thick-walled cysts and nodules in the middle and upper lung zones.
With these findings, think about pulmonary Langerhans cell histiocytosis. However, your patient might be between 30 and 60 years old.
In this case you might see CT findings of ground glass opacities, possibly with centrilobular nodules. In this case, there are two possibilities: respiratory bronchiolitis interstitial lung disease or desquamative interstitial pneumonia.
To tell them apart, you need a BAL, or a lung biopsy. BAL might show brown-pigmented macrophages, known as smokers' macrophages, with no lymphocytes.
On the biopsy, you might see macrophages surrounding the bronchioles, called bronchiolocentric macrophages. In this case, you are dealing with respiratory bronchiolitis-interstitial lung disease.
On the flip side, if BAL shows brown-pigmented macrophages, along with a high number of eosinophils; and the biopsy shows diffuse intraluminal macrophages, that’s desquamative interstitial pneumonia.
Alright, now, let’s switch gears and have a look at iatrogenic ILDs. If your patient has a history of taking medications known to cause drug-induced respiratory issues, such as nitrofurantoin, methotrexate, amiodarone, or chemotherapeutics like bleomycin, you can diagnose drug-induced ILD.

Iatrogenic ILDs 6:05–6:33

However, if your patient has a history of radiation therapy to the chest area, then diagnose radiation-induced lung injury.
Let’s move on to something more challenging, meaning ILDs related to systemic diseases. Patients might present with symptoms of sarcoidosis like fever and weight loss.

Systemic disease 6:33–10:45

On physical exam, you can find features of polyarthritis and erythema nodosum, which refers to red tender skin nodules. If their chest CT shows bilateral hilar adenopathy and bilateral perilymphatic nodules with an upper lobe predominance, consider sarcoidosis.
Next, obtain a lung biopsy, and if it reveals numerous granulomas, diagnose sarcoidosis. Here’s another clinical pearl!
Sometimes, a biopsy isn't necessary to diagnose sarcoidosis. For example, when a patient has an acute onset of fever, erythema nodosum, bilateral hilar adenopathy, and migratory polyarthritis, it's a classic presentation of a rare form of sarcoidosis known as Lofgren syndrome.
Alright, let’s go back to history. Some patients report hand swelling and pain, and they might have noticed that their fingers change color during cold or stress, known as Raynaud’s phenomenon.
The physical exam might show skin thickening or sclerodactyly. A chest CT often reveals a specific pattern known as non-specific interstitial pneumonia, or NSIP, an ILD pattern often associated with connective tissue disease characterized by bilateral lower lung zone ground glass opacities, reticulations, and traction bronchiectasis which is widening of the airways due to surrounding fibrosis, without honeycombing.
In this case, consider systemic sclerosis. To confirm the diagnosis, order labs and test for antinuclear, anti-topoisomerase, and anticentromere antibodies.
If they are positive, you can diagnose systemic sclerosis. Here’s a high-yield fact!
Systemic sclerosis has two main subtypes: diffuse and limited cutaneous systemic sclerosis. ILD is typically associated with the diffuse subtype, while limited cutaneous sclerosis is associated with pulmonary artery hypertension.
Next, patients might present with fatigue, fever, and a skin rash. The physical exam might reveal a malar rash, which is butter fly-shaped skin redness, a discoid rash, or a photosensitive rash induced by exposure to sunlight.
With these findings, consider systemic lupus erythematosus, and order labs including antinuclear, anti-double-stranded DNA, and anti-Smith antibodies.
If they are positive, diagnose systemic lupus erythematosus. In another situation, history might reveal eye and mouth dryness.
On physical exam, you might find conjunctival injection, a decreased salivary pool, and dry mucous membranes. In this case, consider Sjogren syndrome.
Then test for anti-Sjogren syndrome A and B antibodies, known as anti-SSSa and anti-SSB. If they are positive, you've made the diagnosis of Sjogren syndrome.
Finally, if your patient presents with fever, weight loss, abdominal pain, and possibly blood in the urine, while the physical exam reveals palpable purpura, consider microscopic polyangiitis.
To confirm, order labs including antineutrophil cytoplasmic antibodies or ANCA, a urinalysis, and a renal biopsy. If ANCA is positive, especially the perinuclear type called pANCA; urinalysis shows proteinuria and hematuria; and biopsy reveals pauci-immune glomerulonephritis, you can diagnose microscopic polyangiitis.
Here’s another high-yield fact! As you might have noticed, ILD is particularly associated with connective tissue diseases.
Common ones include systemic sclerosis, systemic lupus erythematosus, Sjogren syndrome, rheumatoid arthritis, polymyositis, dermatomyositis, or mixed connective tissue disease.
Now that that’s done, let’s focus on the last category of ILDs, which are the idiopathic ones. First, your patient might be a biological male, over the age of 60, but will have a history of smoking.

Idiopathic ILDs 10:45–12:48

Their chest CT might show a pattern called a usual interstitial pattern of fibrosis, or UIP for short. UIP involves subpleural basal reticulations, traction bronchiectasis, and honeycombing.
If you see these findings, that’s probably idiopathic pulmonary fibrosis. Next, some patients don’t have a history of smoking.
However, if you see NSIP on chest CT, you’re likely dealing with idiopathic nonspecific interstitial pneumonia! Here is one last clinical pearl to keep in mind!
If you are unable to tell apart UIP and NSIP based on the CT scan, get a bronchoalveolar lavage or biopsy to confirm the diagnosis.
Alright, let’s move on to a different scenario. If your patient is initially diagnosed with infectious pneumonia but has not responded to antibiotic treatment, and the CT scan reveals bilateral scattered peripheral consolidations, sometimes with a classic reverse halo sign, you should consider cryptogenic organizing pneumonia.
Next, get a lung biopsy. If it shows buds of granulation tissue inside the lumen of distal airways, diagnose cryptogenic organizing pneumonia.
Okay, in the final scenario, patients typically present with features of idiopathic acute respiratory distress syndrome, meaning acute onset, and rapid progression of shortness of breath and cough as well as fever.
If the CT reveals diffuse bilateral ground glass opacities and septal thickening, consider acute interstitial pneumonia, also known as Hamman-Rich syndrome.
Next, you’ll need a lung biopsy for confirmation. If it shows diffuse alveolar damage, diagnose acute interstitial pneumonia.
Alright, as a quick recap… There are four main categories of interstitial lung disease including exposure-related, iatrogenic, systemic disease-related, and idiopathic ILD.

Review 12:48–13:15

Diagnosing ILD requires a high-resolution chest CT scan. However, to determine the cause, you might need to order additional tests like bronchoalveolar lavage, lung biopsy, or specific antibodies if you suspect a systemic disease.