When should I suspect that my patient might have pulmonary fibrosis?
There are four typical and overlapping presentations of PF:
1. Subacute or chronic cough
2. Exertional dyspnea
3. Concerned patient with a family history of pulmonary fibrosis
4. Incidental PF found on CT imaging
The initial evaluation should include careful chest auscultation for crackles. Please listen carefully halfway down the back at both lung bases as well as in the mid-axillary lines. Drs. Cottin and Cordier have written about the importance of careful auscultation in the early detection of PF. You can listen to crackles online here. If you have access to the NEJM website, you can also listen to crackles here. Examination of the fingers for clubbing can also be helpful in raising the suspicion for PF.
If crackles or clubbing are present, order the following tests at a minimum:
1. PA and lateral chest x-ray
2. Spirometry and DLCO
I also recommend walking the patient in the hallway briskly for ~200 feet or until dyspnea develops. Check pulse oximetry before and after the walk. A decrease in SpO2 of 3-4% or more indicates exertional desaturation and should raise the suspicion of PF. Performing this informal test on a staircase is probably more sensitive than a hallway walk.
The bottom line is that you should have a low threshold to look for PF. Late diagnosis, early misdiagnosis, and suboptimal management strategies are common. PF should be investigated if there is one historical feature suggestive of PF plus one feature from the physical exam or from preliminary testing. Take a look at the figure below. Dyspnea, cough, or a family history combined with one of the "ACES" findings should be enough to move forward with an evaluation for ILD or PF.
What should I do if I suspect my patient might have pulmonary fibrosis?
If you suspect PF, please order a high-resolution CT scan of the chest. I discussed the details of an HRCT in a previous blog post about lung biopsies. Here is the bottom line:
- Supine inspiratory scan with slice collimation no greater than 2 mm (preferably < 1.25 mm)
- At least a few supine expiratory images should also be performed
- High spatial frequency reconstruction algorithm ("Bone" recon on GE machine)
- No IV contrast
Ok. There is evidence of ILD/PF on the HRCT. What do I do next?
Based on the HRCT, you have diagnosed your patient with ILD. The next step is to figure out which kind of ILD your patient has. Here's what I do in my practice:
1. Take a thorough history
In addition to establishing the narrative history, asking the usual questions about dyspnea, cough, and exercise tolerance, and the other standard components of a medical history, I find out about the following:
- History of cancer, chemotherapy, or radiation therapy
- History of cardiac arrhythmias and amiodarone use
- History of prostate, urinary, kidney infections and nitrofurantoin (Macrodantin, Marcobid) use
- All current and prior chronic medications -- don't forget that you can check pneumotox.com to see if your patient's medications might have contributed to their lung condition.
- Symptoms of connective tissue disease (Raynaud's, rash or other skin changes, joints, finger tip changes, heartburn, regurgitation, dry eyes, dry mouth, morning hand stiffness, muscular weakness or pain)
- Exposure to mold sources
- Forced air heating
- Hot tubs
- Visible mold, water damage, or musty odors in the home
- Exposure to birds in the home or in cages; down pillows or comforters
- Exposure to farming or argiculture
- Occupational history with possible dust, fume, vapor, gas, or particulate exposure including:
- Quarry work
- Stone work
- Foundry work
- Heavy metals
- Aerospace industry
- Family history
- Anyone with pulmonary fibrosis/interstitial lung disease or sarcoidosis?
- Anyone ever on oxygen at home?
- Anyone with "autoimmune" diseases, such as lupus, scleroderma, rheumatoid arthritis, or "myositis"
- I also ask about snoring and sleep apnea symptoms.
It is not unusual for me to have a pretty good idea about the specific diagnosis after completing a history and physical exam. Here's what I focus on during the exam:
- Narrow oral aperture (scleroderma)
- Heliotrope rash around the eyes (dermatomyositis)
- Telangiectasias on face & chest (scleroderma)
- Tightening of the skin on the face, chest, and hands (scleroderma)
- JVD and hepatojugular reflux
- Squeaks (hypersensitivity pneumonitis and bronchiolitis)
- RV heave
- Loud P2
- Nail bed sponginess (early clubbing)
- Sclerodactyly and associated changes
- Mechanic's hands (anti-synthetase syndrome)
- Gottron's papules (dermatomyositis)
- Puffy fingers (mixed connective tissue disease/scleroderma)
- Arms & hands
- Synovial thickening on MCPs and wrist
- Joint deformities
- Rheumatoid nodules
- Erythema nodosum (sarcoidosis)
- Pedal edema
- Muscle tenderness (myositis)
- Proximal or distal arm or leg weakness (myositis, steroid effect, deconditioning)
I find rheumatologic serologies to be helpful in quite a few cases. There are certainly many patients I've seen where their rheumatologic serology results helped us avoid a surgical lung biopsy. In many cases, negative serologies help push me to have my patient undergo a surgical lung biopsy. I recommend checking a least a few serologies before performing a surgical lung biopsy.
At a minimum, the following should be checked:
- CBC with differential (for eosinophilic pneumonia)
- Anti-nuclear antibody titer (ANA)
- Rheumatoid factor (RF)
- Anti-cyclic citullinated peptide titer (CCP)
I strongly suggest also performing the following tests in most patients:
- Basic metabolic panel, including calcium
- Creatine kinase (CK)
- Hypersensitivity pneumonitis panel
- Extractable nuclear antibody (ENA) titer (includes antibodies against Scl-70, Jo-1, SSA, SSB, U1RNP, and Smith at my hospital)
- Anti-centromere antibody
- Erythrocyte sedimentation rate (ESR)
- C-reactive protein (CRP)
- Anti-PR3 and anti-MPO antibodies (ANCA antibodies)
Some patients should also have the following tests performed:
- Full myositis panel (if myositis is suspected)
- HIV testing
- Urinalysis and microscopy (for pulmonary-renal syndromes)
- Anti-phospholipid antibodies (anti-cardiolipid antibodies, lupus anticoagulant)
- Anti-RNA polymerase 3 antibodies
All of the tests are back. What do I do know?
Now comes the hard part: you need to combine the history, physical examination, serologies, and HRCT appearance and come up with a unifying diagnosis. If a unifying diagnosis has not been clearly established by this point, you have a few options (listed here from most to least preferred):
Option 1: Refer to an ILD center
I strongly recommend referral to an ILD center -- even for a one-time consultation -- at this point in the evaluation. An ILD center can often help confirm a diagnosis without requiring a surgical lung biopsy. We can also provide guidance on management and help facilitate enrollment in clinical trials. You can find a list of ILD centers on the Pulmonary Fibrosis Foundation's website.
Option 2: Surgical lung biopsy
I think most ILD docs would prefer to provide input before a biopsy is performed, but if you do decide to proceed with a biopsy, please make sure the surgeon takes multiple large biopsies from 2-3 lobes (not just the lingula or middle lobe). Please also have the biopsy reviewed by a pulmonary pathologist with expertise in ILD.
Option 3: Prescribe prednisone
In most cases, I think this is a suboptimal management strategy for ILD that has not been fully characterized. There are some patients (e.g., very sick patients with ILD characterized by ground-glass infiltrates who do not have bronchopulmonary infection) where an "empiric trial" of corticosteroids is reasonable. In most patients, however, this approach clouds the diagnosis, makes subsequent management decisions challenging, and puts the patient at risk for all of the side effects of prednisone (including the 7-fold increased risk of death seen in idiopathic pulmonary fibrosis treated with prednisone).
What else can I do for my patient with PF?
- Assess oxygen requirements at rest, with exercise, and with sleep. Prescribe oxygen (and instructions on its use) to maintain SpO2 > 90% all the time. Tell your patients to buy a pulse oximeter (less then $30 without a prescription) and monitor oxygen saturations right after exertion. Teach your patients to avoid desaturation by dialing up their flow before they exert themselves.
- Prescribe pulmonary rehabilitation
- Screen for sleep apnea
- Vaccinate for influenza and pneumococcus
- Help your patient achieve a healthy weight
- Encourage your patient to join a PF support group (including online support groups, like the one at inspire.com).
- Refer your patient for clinical trial enrollment
- Refer your patient for lung transplantation (it is never too early)
- Tell your patient about all of the PF information available online
- This blog (www.pfdoc.org)
- Jeff Swigris' blog (pulmonaryfibrosisresearch.org/blog)
- The Pulmonary Fibrosis Foundation (pulmonaryfibrosis.org)
Thanks for reading