Introduction: Who Needs Testing and When

Anyone diagnosed with systemic sclerosis (also called scleroderma) should be screened for lung problems, even if they don’t feel short of breath or notice any breathing difficulties. This is because lung damage often starts silently, before symptoms appear, and catching it early allows for better treatment options^[2].

The lungs are among the organs most commonly affected by systemic sclerosis, with studies showing that somewhere between 35% and 65% of people with this condition will develop interstitial lung disease (scarring and stiffening of lung tissue) at some point during their illness^[8][10]. Because lung involvement is one of the leading causes of death in systemic sclerosis, doctors recommend that all patients undergo lung testing from the moment they are diagnosed, regardless of whether they have symptoms^[2].

The risk of developing lung problems is highest in the early years after diagnosis. Certain factors make lung involvement more likely, including being male, being of African-American descent, having the diffuse form of systemic sclerosis (where skin thickening extends above the elbows and knees), testing positive for anti-Scl-70 or anti-topoisomerase antibodies, and having heart problems related to the disease^[8]. However, even people without these risk factors can develop lung disease, which is why screening everyone is so important.

You should seek diagnostic testing immediately if you develop new or worsening symptoms such as increasing shortness of breath, a persistent cough that won’t go away, chest tightness, or difficulty exercising or doing daily activities that were previously easy. These symptoms may signal that lung disease is progressing and needs attention^[11].

Diagnostic Methods for Detecting Lung Problems

Listening to the Chest

One of the simplest ways doctors screen for lung problems is by listening to your chest with a stethoscope during a physical examination. This is called chest auscultation. When listening, the doctor is checking for abnormal sounds, particularly crackling noises called “crackles” or “Velcro crackles” because they sound similar to the tearing of Velcro fabric^[8]. These sounds suggest that the lung tissue is becoming stiff and scarred, which happens in interstitial lung disease.

While chest auscultation is a useful screening tool, it cannot tell doctors how severe the lung damage is or exactly where it’s located. It’s also possible to have early lung disease without any abnormal sounds. Therefore, listening to the chest is just the first step and must be combined with other, more detailed tests.

Breathing Tests

A group of tests called pulmonary function tests or PFTs measure how well your lungs are working. These are essential tools for detecting lung involvement and tracking whether it’s getting worse over time^[8][10].

The most common pulmonary function test is spirometry, which measures how much air you can breathe in and out, and how quickly you can empty your lungs. During this test, you breathe into a mouthpiece connected to a machine that records the measurements. One important number from this test is the forced vital capacity or FVC, which tells doctors the total amount of air you can forcefully exhale after taking the deepest breath possible. When lung tissue becomes scarred and stiff, the FVC goes down because the lungs can’t expand as much^[10].

Another crucial test is the diffusing capacity of the lungs for carbon monoxide, abbreviated as DLCO or DLco. This test measures how well oxygen moves from the air sacs in your lungs into your bloodstream. You breathe in a tiny, harmless amount of carbon monoxide, hold your breath briefly, and then breathe out. The machine measures how much carbon monoxide was absorbed into your blood. In interstitial lung disease, the DLCO is usually reduced because the scarred, thickened lung tissue makes it harder for oxygen to pass through^[2][8].

Doctors use pulmonary function tests not only to diagnose lung disease but also to monitor it over time. Regular testing helps determine whether the disease is stable, getting worse, or improving with treatment. A significant drop in FVC or DLCO over several months is a warning sign that the lung disease is progressing^[8].

Imaging Tests

High-resolution computed tomography, or HRCT, is considered the most important imaging test for diagnosing interstitial lung disease in systemic sclerosis^[8]. This is a special type of CT scan that takes detailed, thin-slice pictures of the lungs, allowing doctors to see the lung tissue in much greater detail than a regular chest X-ray.

On an HRCT scan, doctors can see patterns of scarring and fibrosis in the lungs. They can determine which areas of the lungs are affected, how much lung tissue is involved, and what kind of pattern the scarring follows. This information helps distinguish interstitial lung disease from other lung problems and guides treatment decisions^[8][10].

The extent of lung involvement seen on HRCT is an important factor in deciding whether to start treatment. For example, if the scan shows that more than 20% of the lung tissue is affected by scarring, doctors are more likely to recommend treatment even if symptoms are mild^[10].

A regular chest X-ray is less sensitive than HRCT and may not detect early lung disease. However, it’s sometimes used as an initial screening tool or for monitoring once a diagnosis has been made^[2].

Blood Tests

Autoantibody testing involves checking the blood for specific antibodies that are associated with systemic sclerosis and can help predict which organs might be affected. All patients should have an antinuclear antibody (ANA) test as part of the screening process for systemic sclerosis itself^[14].

More specific antibody tests can provide clues about lung risk. For instance, people who test positive for anti-topoisomerase antibodies (also called anti-Scl-70 antibodies) are at higher risk for developing interstitial lung disease^[8][14]. On the other hand, those with anti-centromere antibodies are more commonly diagnosed with the limited form of systemic sclerosis and may be at higher risk for a different lung complication called pulmonary hypertension (high blood pressure in the lung arteries)^[14].

While antibody tests don’t diagnose lung disease directly, they help doctors understand a patient’s risk profile and plan appropriate monitoring strategies.

Tests for Pulmonary Hypertension

Systemic sclerosis can also affect the blood vessels in the lungs, causing pulmonary hypertension, which is high blood pressure in the arteries that carry blood from the heart to the lungs^[9]. This is a different problem from interstitial lung disease, though both can occur in the same person.

Screening for pulmonary hypertension typically involves an echocardiogram (also called a 2D-echo), which is an ultrasound of the heart. This test uses sound waves to create moving pictures of the heart and can estimate the pressure in the pulmonary arteries^[2][9]. If the echocardiogram suggests high pressure, doctors may recommend a more definitive test called right heart catheterization, where a thin tube is inserted through a vein and guided into the heart to measure pressures directly^[9].

Symptoms of pulmonary hypertension include a fast heartbeat, chest pain, leg swelling, and extreme tiredness. If you develop these symptoms, your doctor should test for this complication^[4].

Other Specialized Tests

In some cases, doctors may examine the fingernails using a technique called nailfold capillaroscopy. This involves looking at the tiny blood vessels at the base of the fingernails under magnification. Certain abnormal patterns in these vessels are associated with systemic sclerosis and may correlate with internal organ involvement, though this test is more commonly used in research settings than routine clinical practice^[2].

A clinical scoring system called the Modified Rodnan Skin Score (MRS) is sometimes used to measure the extent and severity of skin thickening. While this primarily assesses skin involvement, research has shown that people with higher skin scores may be at increased risk for lung problems. This scoring is performed during a physical examination where the doctor assesses skin thickness in different body areas^[2].

Diagnostic Tests Used for Clinical Trial Enrollment

Clinical trials testing new treatments for systemic sclerosis-related lung disease have specific criteria that patients must meet to participate. Understanding these criteria helps explain what tests are considered standard for evaluating lung involvement and determining whether the disease is progressing.

Confirming the Diagnosis

To enroll in most clinical trials, patients must first meet established criteria for systemic sclerosis. The widely used American College of Rheumatology (ACR) 2013 criteria include specific clinical features and laboratory findings that together confirm the diagnosis^[2][5]. These criteria consider factors such as skin thickening, Raynaud’s phenomenon (color changes in fingers with cold or stress), specific antibodies in the blood, and changes in the tiny blood vessels near the fingernails.

Patients with overlap syndromes, where systemic sclerosis occurs alongside other autoimmune diseases, are often excluded from trials so researchers can study a more uniform group of patients^[2].

Demonstrating Lung Involvement

Clinical trials require objective evidence of interstitial lung disease, typically through HRCT scanning. The HRCT must show a pattern consistent with lung scarring. Some trials specify that a certain percentage of lung tissue must be affected—for example, at least 10% or 20% of the lung showing fibrosis on the scan^[8][10].

Pulmonary function tests are also crucial for trial enrollment. Most trials require that FVC and DLCO fall within certain ranges—not so normal that treatment isn’t needed, but not so severely reduced that the disease is too advanced. For example, a trial might require that FVC is between 40% and 80% of the predicted normal value for a person of the patient’s age, sex, height, and ethnicity^[10].

Showing Disease Progression

Many clinical trials specifically seek patients whose lung disease is getting worse, because these are the people who most need new treatments. Progression might be defined as a decline in FVC of 10% or more over a certain time period (often 12 to 24 months), a decline in DLCO of 15% or more, or increasing extent of fibrosis on repeat HRCT scans^[8][10].

The duration and degree of shortness of breath are also considered. Some trials require that patients have symptoms such as shortness of breath during exertion, indicating that the lung disease is affecting their daily lives^[8].

Excluding Other Causes

Before enrolling patients in a lung disease trial, doctors must rule out other conditions that could cause similar symptoms or test abnormalities. For instance, significant pulmonary hypertension can reduce exercise capacity and lung function in ways that mimic interstitial lung disease. Therefore, trials often require an echocardiogram showing that pulmonary hypertension is either absent or only mild^[8].

Other exclusion criteria might include active infections, recent hospitalizations, smoking, or other lung diseases like emphysema or chronic obstructive pulmonary disease (COPD) that could confound the results.

Baseline Testing for Monitoring

Once enrolled in a trial, patients undergo thorough baseline testing that will be repeated during the study to measure whether the experimental treatment is working. This typically includes pulmonary function tests performed at regular intervals (such as every 3 to 6 months), repeat HRCT scans at specified time points, questionnaires about symptoms and quality of life, and tests of exercise capacity such as the 6-minute walk test, where patients walk as far as they can in six minutes while researchers measure the distance^[8].

Some trials also monitor for side effects by checking liver function, kidney function, blood counts, and other laboratory values at each visit. This comprehensive monitoring helps researchers understand both the benefits and risks of new treatments.