Question: Recently I referred a patient with IPF for evaluation for lung transplantation. The center prefers to perform only single lung transplants. I have heard that other centers would consider bilateral lung transplantation for this condition. What is the current best practice for IPF lung transplantation, and are the considerations the same for all the major ILDs?

Answer: This is an interesting question that touches upon several aspects of lung transplantation. The increasing numbers of candidates awaiting lung transplantation far outstrip the supply of available organs. To optimize the use of this resource, single lung transplantation would serve the greatest number of recipients. However, another principle of lung transplantation is to improve survival and quality of life for the recipients. Suppurative lung diseases, such as cystic fibrosis or diffuse bronchiectasis, are absolute indications for bilateral lung transplantation, but for most diseases data on the ideal procedure are not that clear.

In the past several years there has been an increase in the number of bilateral lung transplants performed for diseases previously considered to be indications for single lung transplantation. When the ISHLT (International Society for Heart and Lung Transplantation) registry data for outcomes are compared for single and bilateral lung transplantation, there appears to be a long-term survival advantage for bilateral lung transplant recipients but this is dependent on many factors, such as age of recipient, donor quality and the disease. In patients with COPD under 60 years of age, bilateral lung transplantation had greater survival benefit at 5 years when compared to single. Registry data for patients with IPF undergoing lung transplantation showed a survival advantage at 3 years for single lung transplant recipients younger than 60. There was a higher morbidity and mortality associated with bilateral lung transplantation in the early perioperative period, but when conditional survival (survival to 30d) was evaluated this difference was no longer present.

More recent reports from single centers which use the new allocation system (accounting for increased acuity) and extend the period of observation to 5 years, do show a survival advantage of bilateral lung transplantation in the IPF population. In one study, risk factors for mortality following lung transplant for IPF included single lung transplant and elevated wedge pressure. Some centers advocate the use of bilateral lung transplant for IPF patients who have associated pulmonary hypertension, are under the age of 60, and/or receive organs from an extended donor. This practice is based on extrapolated data from COPD patients and the previously noted higher mortality of bilateral lung transplantation in patients with IPF who tend to be older. However, some authors report good safety results with bilateral lung transplantation in patients older than 60, suggesting that age alone should not exclude bilateral lung transplantation.

Center-specific factors may influence the decision to perform one or the other procedure in the patient with IPF and other interstitial lung diseases such as collagen vascular-associated pulmonary fibrosis or sarcoidosis. The ideal procedure remains an area of controversy.

Selected References

Chang AC, Chan KM, Lonigro RJ, et al. Surgical patient outcomes after the increased use of bilateral lung transplantation. J Thorac Cardiovasc Surg. 2007;133:532-40.

Mason DP, Brizzio ME, Alster JM, et al. Single vs double lung transplantation for idiopathic pulmonary fibrosis. Ann Thorac Surg. 2007;84:1121-1128.

Meyers BF, Lynch JP, Trulock EP, Guthrie T, Cooper JD, Patterson GA. Single versus bilateral lung transplantation for idiopathic pulmonary fibrosis: A ten-year institutional experience. J Thorac Cardiovasc Surg. 2000;120:99-107.

Meyer DM, Bennett LE, Novick RJ, Hosenpud JD. Single vs bilateral, sequential lung transplantation for end-stage emphysema: influence of recipient age on survival and secondary endpoints. J Heart Lung Transplant. 2001;20:935-941.

Rinaldi M, Sansone F, Boffini M, et al. Single versus double lung transplantation in pulmonary fibrosis: a debated topic. Transplant Proc. 2008;40:2010-2012.

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Question: I am treating a patient with IPF who is showing signs of depression. As a pulmonologist, I am reticent to treat this comorbidity but I believe she would benefit from therapy. Who would be the best point person to manage her psychiatric issues?

Answer: Idiopathic Pulmonary Fibrosis, a progressive illness leading to respiratory insufficiency, is well known to affect patient's quality of life in the physical as well as emotional domains.

Although limited, studies have demonstrated significant negative feelings or depressive symptoms in about 20-25% of patients with IPF. With progressive respiratory insufficiency, patients may develop fatigue, sleep disturbances, muscle weakness, and decreased appetite. It is important to distinguish these symptoms from true depressive affect or despondency that may overcome our patients. Several steps can be taken that may help your patient:

• Sleep studies and interventions for abnormal patterns (obstructive sleep apnea, restless leg syndrome or fragmented sleep with associated hypoxemia) may prove salutary to the patient¹
• Pulmonary rehabilitation and physical therapy may lead to improvement in emotional and physical well being (improved dyspnea and 6MWT)²
• Support groups can reduce feelings of isolation and may provide useful coping mechanisms

Continued interest in the emotional state of our patients and openness to discuss their concerns and worries will offer welcome support. When appropriate, QOL questionnaires can help assess the development of symptoms and permit early intervention.³

However, certain patients require psychotherapy and/or psychiatric medication. One tool that has been used to screen for depression is a simple 2-part question⁴:

During the past month:
1. Have you often been bothered by feeling down, depressed, or hopeless?
2. Have you often been bothered by having little interest or pleasure in doing things?

If you suspect that your patient suffers from affective disorder, you should refer her for expert evaluation. It is important to communicate with the therapist and discuss the patient's respiratory state, the associated limitations, and the dismal prognosis of IPF. Antidepressant medications may have sleep or respiratory side effects which are both of concern in patients with IPF.

1. Krishnan V, McCormack MC, Mathai SC, et al. Sleep quality and health-related quality of life in idiopathic pulmonary fibrosis. Chest. 2008;134;693-698.
2. Nishiyama O, Kondoh Y, Kimura T, et al. Effects of pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis. Respirology. 2008;13:394-399.
3. De Vries J, Kessels BL, Drent M. Quality of life of idiopathic pulmonary fibrosis patients. Eur Respir J. 2001;17:954-961.
4. Ebell MH. Routine screening for depression, alcohol problems, and domestic violence. Am Fam Physician. 2004;69:2421-2422.

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Question: I have a patient with IPF whose condition has worsened over the past few weeks. I believe that "acute exacerbations of IPF" describes my patient well; she has a rapid deterioration of PFTs and quality of life and is requiring higher concentration of oxygen. What can be done to help her or slow the decline?

Answer: Patients in all stages (early, moderate, advanced) of IPF are at risk of developing acute decompensation of their clinical condition. They may present with progressive dyspnea, cough, and/or low grade fever. Deterioration in function may be caused by opportunistic infection (viral, bacterial, or fungal); ischemia/congestive heart failure; thromboembolism; aspiration; barotrauma or acute exacerbation of IPF. This last term is reserved for a decline in function over a short period, usually weeks, associated with well-defined diagnostic criteria:

1. Increasing dyspnea or cough within one month in patient with IPF
2. Newly developed pulmonary opacities on chest x-ray or ground glass densities on HRCT superimposed on findings consistent with a UIP pattern
3. Increasing oxygen requirements: decrease in PO₂ (> 10 mm Hg) or saturation under similar conditions
4. Exclusion of other causes of respiratory distress: CHF, cardiac ischemia, thromboembolism, barotrauma, aspiration, conditions that may lead to ARDS (pancreatitis, sepsis), infection
5. Some authors also include a significant decline in FVC (> 10 % absolute decrease)

Thus, a systematic approach should be taken with a patient with IPF and worsening respiratory status. The evaluation should include thorough history, ABGs/saturation, PFTs, HRCT (CT angio when possible), echocardiogram, serologic studies for viruses or atypical organisms, sputum cultures and if safe, BAL.

The incidence of acute exacerbation is not well established but it has been estimated to occur in about 5-19% of patients with IPF.¹ It may be the presenting manifestation or occur at any stage of disease and is independent of degree of physiological impairment. In patients undergoing surgical biopsy, the predominant histologic finding is diffuse alveolar damage superimposed on UIP. The morbidity and mortality of this complication is high. It was initially described in patients with acute respiratory failure, where mortality was over 90% at 60 days. A recent systematic review estimates the mortality to be 60% at 1 month and 67% at 3 months.²

An effective treatment for acute exacerbation does not exist. Recognition of acute exacerbation at an early stage has allowed for interventions geared toward avoiding respiratory failure. Responses to pulsed corticosteroids, immunosuppressants (cyclosporine, cytoxan), antifibrotics (pirfenidone), and anticoagulants in combination with or after antibiotics have been reported. Novel therapies such as hemoperfusion with polymyxin B-fiber column have been utilized with some success. Survivors of an acute exacerbation may be left with further decrement in their functional ability and with greater physiologic impairment.

The unpredictability of acute exacerbations, the dismal prognosis and the adverse impact on the course of IPF make it imperative to be vigilant for this complication, to treat infection rapidly, and to intervene promptly. Evaluation for lung transplantation is recommended prior to the onset of an acute exacerbation.

1. Hyzy R, Huang S, Myers J, Flaherty K, Martinez F. Acute exacerbation of idiopathic pulmonary fibrosis. Chest. 2007:132:1652-1658.
2. Agarwal R, Jindal SK. Acute exacerbation of idiopathic pulmonary fibrosis: a systematic review. Eur J Intern Med. 2008;19:227-235.

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Question: I recently moved my practice to New Mexico. I keep getting lung biopsy results which say "foreign polarizable material and noncaseating granulomas." I'm unfamiliar with this nomenclature and haven't been able to contact the pathologist. Is this finding known by another name? All cultures and serologies are negative. Any thoughts on what I should do about these patients?

Answer: "Foreign polarizable material" is a descriptive term that further characterizes the nature of noncaseating granulomas on tissue biopsies. It refers to the presence of birefringent material revealed by polarizing microscopy at sites of granuloma formation. It should alert clinicians to the possibility of inhaled or circulating foreign substances such as talc, mica, aluminum, calcium, beryllium, etc that may provide a clue to the diagnosis. Endogenous material (calcium silicate or carbonate) may also polarize and not represent true "foreign material." It is sometimes possible to identify the polarizing material, particularly if it is abundant. Electron probe microanalysis can be used for this purpose.

Diagnosis of sarcoidosis by biopsy is a diagnosis of exclusion. Some feel that the presence of foreign bodies discovered by polarizing microscopy excludes the diagnosis of sarcoidosis. Yet other authors believe that the foreign material may be the allergen that stimulated the development of sarcoidosis in patients with this predisposition.

A patient with the finding of foreign body noncaseating granulomas should have a thorough history taken for occupational, recreational, or inhalational exposures; nasal insufflation of oils or topical substances; and for use of illicit drugs (cocaine). GERD with aspiration should also be excluded. If these are negative, a diagnosis of sarcoidosis should not be excluded, especially if other findings support it. A discussion with your pathologist will be helpful in reaching a final diagnosis.