What is Nonspecific Interstitial Pneumonia?
Nonspecific interstitial pneumonia, or NSIP, is a type of lung disease that falls under the broader category of conditions called idiopathic interstitial pneumonia (IIP). These diseases affect the tissue between the air sacs in your lungs. In the case of NSIP, it causes long-term damage and inflammation in these spaces. The word “nonspecific” is used because this form of pneumonia doesn’t have any specific features that would categorize it as a certain kind of IIP. It usually affects both lungs and often shows more impact on the lower part of the lungs.
What Causes Nonspecific Interstitial Pneumonia?
Nonspecific interstitial pneumonia (NSIP) is a lung condition that can either arise on its own (idiopathic) or be associated with other diseases, infections like HIV, exposure to toxins, or numerous other causes. What “nonspecific interstitial pneumonia” means is that the lung tissue between the air sacs, also known as the “interstitium,” becomes inflamed without a specific, identifiable cause.
There are a few possible secondary causes for NSIP:
1. Connective tissue disease (CTD): This is an illness that affects the parts of your body that connect your tissues and organs, like collagen and elastin. NSIP is often connected with these diseases, which include systemic sclerosis, polymyositis/dermatomyositis, rheumatoid arthritis, and Sjogren syndrome.
2. Medication induced: Certain medications like Amiodarone, methotrexate, nitrofurantoin, chemotherapy drugs, and statins, have been associated with NSIP.
3. HIV infection: This a less common source these days, thanks to the widespread use of antiretroviral therapy to manage HIV.
4. Interstitial pneumonia with autoimmune features: This refers to those patients who show NSIP on a lung biopsy, and have signs of an autoimmune disease (a disease where your body’s immune system attacks your own cells), but don’t fit specifically with connective tissue disease.
In some patients, lung biopsies might not show granulomas (areas of inflammation in the body), and the condition might resemble NSIP under a microscope. Other diseases that might be related to NSIP include IgG4-related systemic disease (a kind of inflammation across different parts of the body), familial interstitial pneumonia (a hereditary form of lung disease), and graft versus host disease (a condition that can occur after a transplant).
Risk Factors and Frequency for Nonspecific Interstitial Pneumonia
Non-specific Interstitial Pneumonia (NSIP) is a relatively rare disease. It accounts for between 14% and 36% of cases of a condition known as idiopathic interstitial pneumonia. While it’s not as common as usual interstitial pneumonia (UIP), which makes up 50% to 60% of cases, it’s more common than desquamative interstitial pneumonia, respiratory bronchiolitis-associated interstitial lung disease (10-17%) and acute interstitial pneumonia (0% to 2%). NSIP without a known cause mostly affects middle-aged women who don’t smoke. However, when NSIP is related to connective tissue disease, it affects men and women equally.
- NSIP is a rare disease.
- It accounts for 14% to 36% of cases of idiopathic interstitial pneumonia.
- Usual Interstitial Pneumonia (UIP) is more common than NSIP, representing 50% to 60% of cases.
- NSIP is more common than both desquamative interstitial pneumonia, respiratory bronchiolitis-associated interstitial lung disease (10-17%) and acute interstitial pneumonia (0% to 2%).
- NSIP without a known cause is most common in middle-aged, non-smoking women.
- When NSIP is caused by connective tissue disease, it affects men and women equally.
Signs and Symptoms of Nonspecific Interstitial Pneumonia
When someone has this condition, they may experience a number of symptoms that gradually get worse over time. The most common ones include breathing difficulties and a cough. They may also have a fever, lose weight, and exhibit flu-like symptoms. If they also have connective tissue disease (CTD), they might have dry mouth, dry eyes, joint pain or swelling, muscle pain, problems swallowing, skin changes, and other related symptoms.
- Breathing difficulties and progressive cough
- Fever
- Weight loss
- Flu-like symptoms
- Dry mouth or eyes (if CTD is also present)
- Joint pain or swelling (if CTD is also present)
- Muscle pain (if CTD is also present)
- Difficulty swallowing (if CTD is also present)
- Skin changes (if CTD is also present)
During a physical examination, a doctor might notice fine crackling sounds, particularly in the lower parts of the lungs. About 10% to 35% of people may also have clubbing (widening and rounding of fingers or toes). Other potential signs might include the features of rheumatological disease such as skin changes and joint swelling.
- Crackling sounds in the lungs, especially at the bases
- Clubbing of fingers or toes (in 10% to 35% of cases)
- Skin changes (linked to rheumatological disease)
- Joint swelling (linked to rheumatological disease)
Testing for Nonspecific Interstitial Pneumonia
If your doctor suspects that you may have a lung condition called non-specific interstitial pneumonia or NSIP, there are several steps they will take to assess your health.
The first step is a clinical evaluation. This involves asking you detailed questions about your health history, your lifestyle, any medicines you’re taking, if you’ve been exposed to certain allergens or radiation, if you have any risk factors for HIV or symptoms of connective tissue disease (CTD), and any family history of lung diseases.
They may also order some lab tests. If your doctor suspects that you might have a connective tissue disease – diseases that affect your body’s connective tissues including your skin, joints, muscles, and blood vessels — they might ask for a special blood test to confirm it. If your exposure history and lifestyle suggest you may be at risk of HIV, your doctor might also suggest an HIV test.
Your doctor will also conduct some breathing tests, known as Pulmonary Function Testing (PFT). This involves different types of tests: Spirometry measures the amount of air you can breathe in and out and at what speed; Lung volume test measures the total amount of air your lungs can hold; Diffusing capacity of the lung for carbon monoxide (DLCO) test measures how well the oxygen you breathe in moves from your lungs to your blood; and a 6-minute walk test can determine if you have difficulty breathing during physical activity. All these tests together will help the doctor to know how severe your condition is, how it’s progressing over time, and how effective the treatment is. People with NSIP often have a reduction in the amount and speed of air they can breathe in and out, as well as a reduced ability to transfer oxygen from their lungs to their blood.
Another important way to check for NSIP is using imaging tests. A chest x-ray can provide a simple image of your lungs, but the preferred test is a High-Resolution Computed Tomography or HRCT scan. This gives a detailed 3D image of your lungs and can show common signs of NSIP such as thicker lung tissue, a condition called ‘traction bronchiectasis,’ loss of lung volume or signs of inflamed and scarred lung tissue mainly in the lower zones of the lungs.
In some cases, a lung biopsy may be needed to confirm the diagnosis of NSIP. This is a procedure where a small piece of lung tissue is removed and examined under a microscope. But whether or not you need a biopsy will depend on your overall health, the severity of your lung condition and if there is any clear reason for your lung condition like a connective tissue disease or a reaction to a medication.
Treatment Options for Nonspecific Interstitial Pneumonia
The treatment for NSIP (Non-specific Interstitial Pneumonia) depends on the cause specifically and how severe the disease is.
If the disease is mild, the patient will usually show mild symptoms and their lung function tests will show minimal changes. These patients might not need immediate treatment, but they should be closely watched to look out for any signs that the disease might be progressing.
Patients with moderate to severe NSIP have more intense symptoms and their lung function tests show noticeable change. These patients usually receive treatment through a medication called prednisone, which is a type of steroid. The doctor will monitor the patient’s response to prednisone and how well the person tolerates it for 3 to 6 months. If prednisone isn’t effective, then other drugs which suppress the immune system, like azathioprine or mycophenolate, could be used. Occasionally, if the disease is more severe, a patient might be given prednisone along with another immune-suppressing drug from the start.
In the most severe cases, patients may require hospitalization. During their stay, the patient might receive high dose prednisone treatment over three days, followed by regular prednisone treatment. If the disease doesn’t improve despite the use of steroids and immune-suppressing drugs, doctors may consider other treatments such as cyclophosphamide, rituximab, or calcineurin inhibitors. Sometimes, lung transplantation may be recommended. Doctors will also be mindful to check for potential side effects from steroid therapy, and to weigh up the benefits and risks of continuing the treatment. Also, patients receiving high dose of prednisone for more than a month or receiving multiple types of immunosuppressive drugs are at risk of getting a particular type of pneumonia (Pneumocystis jirovecii pneumonia), so they could be given additional drugs to help protect against this.
Sometimes NSIP can be caused by some other underlying conditions like drugs, connective tissue disease, or HIV infection. In these cases, addressing these underlying conditions may help improve the NSIP. For drug-induced cases, removing the drug can sometimes help. For connective tissue disease, the focus will be on treating that disease, and it may be beneficial to collaborate with a rheumatology specialist. For HIV infection, the first steps would be treating any infections and then starting antiretroviral therapy. Steroids can be used if there isn’t any improvement.
What else can Nonspecific Interstitial Pneumonia be?
There are different types of lung conditions that can sometimes be confusing due to their similar features:
- One of these conditions is idiopathic interstitial pneumonia which includes two subtypes: usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). It can be tough to tell them apart because they share some clinical and structural characteristics. But, NSIP has a more favorable outcome and it can potentially respond well to steroid therapy.
- Hypersensitivity pneumonitis is another condition that can be complicated to identify. In its early phases, typical signs include small nodules in the middle of the lung lobules and predominant involvement of the upper lung zones. When examined under a microscope, the bronchioles, or small airways in the lung, are seen to contain large cells and poorly formed groups of immune cells (granulomas). This condition can become more fibrotic over time, so it’s important to consider this when reviewing the patient’s clinical history and deciding on further evaluation.
- Patients with a disease related to an immune protein called IgG4 can also have a type of lung disease. In such cases, a microscopic examination of the lung tissue can show the presence of IgG4-positive cells within the lung’s structural framework. This finding can help physicians differentiate this condition.
What to expect with Nonspecific Interstitial Pneumonia
The outlook for NSIP (Nonspecific Interstitial Pneumonia) is much better than that for UIP (Usual Interstitial Pneumonia). Among patients with UIP, survival rate is about 43% for five years and only 15% for ten years. In contrast, roughly 86% to 92% of NSIP patients survive for five years, and 26% to 40% make it to the ten-year mark.
Within NSIP, there are different types. Fibrotic NSIP, which involves more severe scarring in the lungs, is thought to have a worse outlook than the inflammatory, cellular type of NSIP, which is characterized by inflammation and increase of cells in the lungs.
