Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) is a chronic progressive fibrotic process involving the lung parenchyma. It is generally not seen before age 40. There is no known unifying cause but risk is increased with cigarette smoking, viral infection, environmental pollution, chronic aspiration, genetic predisposition, and certain drugs. None of these adequately explain this typically fatal disease. The prominent pathologic features include disorganized progressive deposition of collagen, extracellular matrix, and inflammatory cell infiltrate which result in distorted pulmonary architecture. The thickened alveolar-capillary membrane, disrupted capillary bed and reduced alveolar space surface area lead to the reduced oxygen diffusion commonly seen. Patients typically lose 150-200mls of FVC per year. Oxygenation becomes difficult and high flow 02 is needed as disease progresses. Dyspnea and dry cough are the major symptoms. PFT’s are restrictive with a reduced DLCO. Occasionally a small obstructive component is seen. CXR reveals diffuse asymmetric interstitial thickening (scarring) and subpleural cysts. The prognosis is poor, with only 20-30% of patients surviving five years.
Treatment efforts up until this past year have been mostly ineffective. The mainstay has been corticosteroids since they are known to inhibit scar formation. Numerous drugs have been studied and used including acetylcystiene, cyclophosphamide, azathioprine, anti-tnf drugs, interferon, etc. None of these have been proven to be effective. Oxygen is given at whatever flow or concentration is needed. Any coexisting lung disease such as COPD, or respiratory tract infections should be treated. Cough suppression may provide some comfort. Oral narcotics or benzodiazepines are sometimes used for palliative care. Lung transplant may be offered to suitable candidates.
Over the past year two new drugs (finally!) have become available which have been shown to slow the loss of FVC significantly. Perfenidone (Esbriet) inhibits transforming growth factor beta (TGF-b) which reduces fibroblast proliferation. Several clinical trials have shown a reduction in death, exacerbations, and loss of FVC over at least a 52 week period. It is taken orally three times a day. Side effects may include rash, nausea, diarrhea, and fatigue being some of the most common (>20% of patients). The second new drug to become available is Nintedanib (Ofev) which is a receptor blocker for multiple tyrosine kinases that mediate fibrogenic growth factors. This drug has also been shown to reduce rate of FVC loss and time to first exacerbation. This drug is taken two times a day. Side effects may include diarrhea and nausea both occurring in over 20% of patients.
If indeed these medications have the desired positive effects respiratory therapists may have more exposure to these patients. Depending on the care setting the therapist can provide means to assure adequate oxygenation at rest and with ambulation delivering whatever is needed to keep the Sa02 >86% which may not be possible at some point. Mechanical ventilation has never been shown to be of benefit. Only a few percent ever survive and those are the patients who did not go on the ventilator as a result of their pulmonary fibrosis, (e.g. surgery). Non-invasive ventilation has been used as palliation with mixed results. This could now change if indeed these patients are surviving longer which would increase the odds of them needing ventilation for other reasons such as pneumonia, surgery, coexisting COPD or CHF to list a few. One very important role in my opinion is to serve as educator for other care givers. Although pulmonary fibrosis has almost nothing in common with COPD, I am surprised how often this is not appreciated by care providers. IPF doesn’t behave like COPD, and does not improve with COPD medicines. The lung exam is completely different in that the patient will generally have diffuse harsh inspiratory crackles (rales), and wheezing is not typical.
After fifty years of failed treatments, we finally have two medications which may clearly make an impact on the progression of IPF. This is wonderful news for patients and pulmonary doctors alike. Our ever important ongoing goal is to make sure that these patients are properly diagnosed, evaluated, and treated before to the disease becomes severe.
Doug Kane M.D. FACCP