Question: What are PFT, SpO₂, ABG, and other relevant criteria for allowing airplane travel for patients with advanced IPF?

Answer: There are no strict PFT criteria for airplane travel but there are some clues which would indicate the need for oxygen during travel. For example, desaturation during a 6-minute walk test and a diffusing capacity < 35% of predicted suggest the need for oxygen during flight. Neither the resting SpO₂ nor resting ABG is useful unless the patient is hypoxemic at rest, quite unusual even in patients with severe IPF. We do altitude simulation studies in most or all patients who we think may need oxygen during flight. To accomplish this, the patient is placed in a reduced FiO₂ chamber (16%) which corresponds to a plane pressurized to 8,000 ft (all planes are now pressurized to 7,000-8,000 ft). SpO₂ is monitored for 25 minutes followed by ABG at the end of the test. If PaO₂ is less than 55 mm Hg or 88%, we recommend O₂ during flight.

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Question: Currently, what is the best line of management for IPF? How accurate is the histopathological diagnosis of the condition, keeping in mind the grave prognosis of the irreversible condition?

Answer: Since there are currently no approved drugs for the treatment of IPF, the best approach is to enter a patient into a clinical trial. However, the pirfenidone trial is closed and the bosentan trial is closing imminently so the only active trials are those sponsored by the NIH (IPF Network). One trial is for patients with mild to moderate disease who will be randomized to placebo vs NAC (N-acetylcysteine) vs Prednisone/Azathioprine/NAC. This trial follows a study by Demedts M, High-dose acetylcysteine in idiopathic pulmonary fibrosis (N Engl J Med. 2005;353:2229-2242), which showed Pred/Aza/NAC preserved FVC and DL_CO in IPF patients compared to placebo treatment. The second IPFnet trial is looking at whether sildenafil will abate pulmonary hypertension in patients with advanced IPF and improve 6-minute walk test performance. The histopathologic diagnosis is still the "gold standard" but should be looked at in the clinical context. We have seen several cases where the biopsy analysis shows UIP but the HRCT has more ground glass than usual and only minimal or no honeycombing. This may be a sampling problem if the biopsy specimen is from a scar area, but it also may reveal comorbid NSIP and IPF, which may be more responsive to prednisone and immunosuppressive therapy than IPF alone. If there is honeycombing on HRCT there is a greater than 85% likelihood that the patient has IPF, so biopsy is not necessary.

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Question: What nonpharmacologic treatments can help IPF patients and what are some important comorbidities that need to be addressed?

Answer: The two major challenges in patients with IPF are control of cough and maintaining an adequate level of exercise and physical activity in the face of profound dyspnea. We treat cough aggressively with low dose prednisone and control GERD (all patients should be on a PPI even if though do not have symptoms because over 70% of patients with IPF have reflux). Codeine-containing narcotics, tessalon perles, and occasionally, inhaled corticosteroids and bronchodilators are of benefit. Still, cough can be crippling and novel suppressors of cough are being sought. Also, ALL patients with IPF should enter a formal pulmonary rehabilitation program for 6–8 weeks, followed by maintenance. These programs are proving to be critically important for increasing exercise tolerance, well-being, muscle strength, and may improve survival. Learning to exercise with or without oxygen, learning how to regulate and control breathing, and the support network all make rehabilitation a key nonpharmacologic therapy for IPF patients. Comorbidities, such as GERD, sleep apnea, and pulmonary hypertension (PH), also need to be addressed. The diagnosis, significance, and treatment of PH will be addressed in other PILOT features.

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Question: When should a patient with IPF be referred for a workup for lung transplant and when is the best time to transplant?

Answer: A patient who is eligible should be referred for lung transplant upon diagnosis of IPF. Since the course of IPF is unpredictable with possible acute exacerbations and rapid deterioration, the patient should be evaluated for treatment and workup completed early in the disease. We don't know the "perfect" time for transplant in large part because only 50% of patients are alive 5 years after transplant. Clinicians and transplant physicians should jointly pick the optimal time, generally when functional status is good but there is clear evidence of progression. Also, when FVC < 40–50% and DLCO < 30–35% of predicted, waiting may entail high risk. Patients at some centers are considered for transplant up to 70 years of age, so age alone is not a barrier anymore.

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Question: Who with interstitial lung disease should undergo a surgical lung biopsy?

Answer: This is somewhat controversial but our rule-of-thumb is that anyone with ILD who is less than 40 years of age should undergo a surgical lung biopsy. IPF is less common in this age group but still occurs. Even with an HRCT that is classic for IPF, ie, honeycombing with minimal ground glass, traction bronchiectasis, and reticular abnormalities, we recommend biopsy in younger patients. In those over 40 with a classic HRCT and clinical presentation (insidious onset, crackles on exam, no known exposure or evidence of autoimmune disease) biopsy is not necessary.

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Question: The EPA has recognized that exposure to diesel exhaust can lead to pulmonary fibrosis. Using the American Thoracic Society (or any other reliable qualifiers), how does one refer to that disease? Is it still idiopathic, if causation is known, or is "idiopathic" dropped once cause is determined? Please refer to published articles, if possible.

Answer: The EPA has shown that exposure to diesel exhaust can lead to pulmonary fibrosis, but it has been confirmed only in animal models. There are no human studies that corroborate the animal work. It is a potential but unproven cause of pulmonary fibrosis. A nice review by JC Bonner, "Lung fibrotic responses to particle exposure," recently appeared in Toxicologic Pathology. 2007;35:148-153. (Click here for abstract) On the other hand, exposure to asbestos is a known cause of pulmonary fibrosis. Therefore, if a patient reports exposure to high concentrations of diesel exhaust alone and has fibrosis, the diagnosis would still be IPF.

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Question: What is your approach to patients who have focal areas of honeycombing or fibrosis in the absence of history of pneumonia? Is there an approach to seeing if they're developing IPF? How often would one repeat a CT or PFTs in this situation?

Answer: In patients with focal honeycombing or fibrosis, we adopt a watchful waiting approach. Even if the patient does not have a history of pneumonia, focal scar is not uncommon with previous infection or a possible environmental insult. We recommend following PFTs every 6 months for approximately 2 years and if there is any significant reduction in FVC (> 5%) or DL_CO (> 5-10%), I would follow-up with a repeat HRCT. Even though HRCT is almost 5X less radiation than a conventional CT, we still need to be cautious prior to recommending its use on a frequent basis.

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Question: What is Burkholdi?

Answer: Burkholdi species are gram negative organisms with the most common being Burkholderia cepacia, which is common in patients with cystic fibrosis. It can also be found in patients with severe bronchiectasis such as IPF patients. It is difficult to treat and frequently resistant to antibiotics but carbapenems (eg, meropenem) and aminoglycosides (eg, tobramycin) are the preferred antibiotics. Infection with this organism is associated with decreased survival.