Question: My doctor tells me that my construction job has contributed to my pulmonary fibrosis. Is this true? Should I change jobs?

Answer: First of all, this is a complicated question that depends on many aspects of the job and what kind of "pulmonary fibrosis" is present. The best way to answer the question is to explore some of the occupational interstitial lung diseases. For starters, we know that some kinds of dust can cause pulmonary fibrosis.

One common cause is asbestos, which is being systematically removed from many old buildings. An exposure to asbestos sufficient to cause pulmonary fibrosis comes with daily exposure for many years to a significant dust burden. This can be seen in automobile brake workers, plumbers, and demolition experts who do not wear masks. The lung disease is called "asbestosis." If an x-ray shows calcium deposits along the pleura (the outside lining of the lung), asbestosis is suspected.

Another mineral that can cause lung disease is silica, which is different from silicone. Silica is a hard rock that is the principle component of sand and quartz. Therefore, quarry workers, sandblasters, and others with exposure to rock dust have a risk for this disease. The disease "silicosis" is characterized by small nodules that are most common in the upper parts of the lung.

Other minerals can also cause lung disease. Found in hardened metals, cobalt causes giant cell interstitial pneumonitis, a disease with a characteristic biopsy. Coal causes coal worker's pneumoconiosis, a disease that is much more symptomatic when mixed with silicosis.

Last, it has been noted that idiopathic pulmonary fibrosis (IPF) is seen more commonly in some occupations that have contact with dust. Whether there is some particular component of dust that scars the lungs, or whether IPF is the result of a more generalized response to a dusty environment remains unknown. Unfortunately, there is no information on whether removal from a dusty environment is beneficial to an established IPF patient. The general recommendation of working in a clean air environment makes some common sense, but has never been subjected to study.

Question: I never know when to order an antinuclear antibody (ANA) or rheumatoid factor (RF) test on my interstitial lung disease (ILD) patients or what to do with a positive test. Please help!

Answer: Many pulmonary physicians choose to screen for occult connective tissue disease (CTD) with a variety of laboratory tests. The practice has evolved from the knowledge that 10% to 25% of ILD patients will eventually be diagnosed with a CTD; however, the frequency with which ILD is the only manifestation of a CTD remains unknown. Usually a CTD will evolve in the first 2 years following ILD presentation in these patients.

Older data has suggested that the frequency of ANA and RF positivity in idiopathic pulmonary fibrosis (IPF) is approximately 40%. More recent case series have suggested that many of these patients do not meet high resolution computed tomography (HRCT) or open lung biopsy criteria for usual interstitial pneumonitis (UIP), the pathologic correlate of IPF, and more typically have nonspecific interstitial pneumonitis (NSIP) in which lung fibrosis is more diffuse but less progressive.

Therefore, when a patient has a positive RF, particularly if arthritis is present, then further work must be done. A new test for anticyclic citrullinated peptide antibodies (Anti-CCP) is both more sensitive and specific for rheumatoid arthritis. Hand films and films of affected joints are obtained to solidify diagnosis. Importantly, if RA can be confirmed, anti-inflammatory therapy will be begin with a goal of reducing joint (and lung) inflammation. Most commonly, this will require a tumor necrosis factor (TNF) inhibitor when RA is advanced sufficiently to have ILD.

The utility of ANA is less well studied. ANA is almost always positive in systemic lupus erythematosis, scleroderma, CTD-associated Sjögren's syndrome, and often positive in polymyositis/dermatomyositis. If ANA is positive in ILD at a titer of 1:160 or higher, further characterization of an extractable nuclear antigen (ENA) panel is recommended. This panel can further characterize the disease and suggest the most appropriate anti-inflammatory therapy.

Although these laboratory tests are inexpensive and felt to be helpful, no prospective study has ever determined if the tests truly make a difference independent of a good history and physical exam.

Question: I am a PCP with a 72 y/o patient. The pulmonologist made a diagnosis of IPF based on radiologic findings. She stressed the extensive honeycombing of the lungs. What is honeycombing and what is the underlying physiology?

Answer: This is the million dollar question to the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF). Briefly, honeycombing is a word applied to the appearance on the computed tomography (CT) scan that applies to the development of adjacent cystic airspace enlargement, usually in a subpleural location. As pulmonary specialists and radiologists, we use many words that do not have formal definitions and "honeycombing" is one of these words. In brief, it looks like a "honeycomb."

Airspace enlargement is common to many diseases. The best known of these is emphysema in which airspace enlargement (holes in the lung) is not associated with any surrounding fibrosis. A lung bullous is a large (> 3 cm diameter) area of emphysema. Lung cysts, in contrast, are areas of airspace enlargement with surrounding fibrosis. Cysts are seen in a variety of infectious lung diseases (eg, tuberculosis), cystic fibrosis, and some of the rarer diffuse parenchymal lung diseases such as lymphangioleiomyomatosis (LAM) or pulmonary Langerhans cell histiocytosis (PLCH).

When cystic lung disease is adjacent to the pleura and surrounded by areas of fibrosis, open lung biopsies have suggested that these cystic airspaces are the result of interstitial lung fibrosis that is pulling the lung apart. The holes that are left have distorted architecture and excess mucus inspisation; however, the pathology is not the hole, but the scarring in the lung characterized by excesses of fibroblasts. Therefore, if a novel therapy for IPF were found tomorrow, the impact of that drug on honeycomb fibrosis is not likely to be the mechanism of improvement. However, if milder degrees of fibrosis are present elsewhere in the lung before lung distortion occurs, then such a medication would have a better opportunity to work.

When radiologists are asked to define "honeycombing" they often do not agree, particularly in mild disease. However, your consultant is impressed with the amount of honeycombing, and large amounts of honeycombing are almost universally associated with a lung biopsy finding of usual interstitial fibrosis (UIP), the pathologic entity associated with IPF.

I would make the point that some diseases can have honeycombing (UIP) and not be IPF. Interstitial lung disease due to rheumatoid arthritis, radiation fibrosis, asbestosis, and some forms of chronic hypersensitivity pneumonitis (bird fancier's disease, hot tub lung, or farmer's lung, for example) will also have this appearance. Therefore, patients with extensive honeycombing should still be asked about connective tissue disease symptoms, and exposures to organic antigens (eg, birds, hot tubs, moldy hay) in their evaluation, since control of these may prevent progression of lung disease.

In summary, I agree that extensive honeycombing suggests the probable diagnosis of IPF and is usually sufficient for entry into a treatment trial for this disease. We all hope that new therapies will soon be available for IPF.