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New Brunswick, NJ
Dr. Riley is Professor of Medicine, UMDNJ-Robert Wood Johnson Medical School.
Correspondence to: David J. Riley, MD, FCCP, Professor of Medicine, Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Room C-B04, Piscataway, NJ 08854-5635; e-mail: riley{at}umdnj.edu
The idiopathic interstitial pneumonias (IIPs) are a heterogeneous group of disorders resulting from damage to the lung parenchyma by varying patterns of inflammation and fibrosis.1 A consensus classification system of IIPs1 includes the following entities: idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and lymphoid interstitial pneumonia. Since these entities differ in prognosis and response to therapy, an accurate diagnosis is required. In the absence of typical clinical and radiographic features of IPF or if there is uncertainty about the diagnosis, a surgical biopsy is often indicated.
A decision about lung biopsy should be individualized, taking into consideration the risks of the operation and the potential benefits of establishing the diagnosis. The risk of open-lung biopsy or video-assisted thoracoscopic surgery (VATS) for interstitial lung disease is low. Overall mortality for a variety of indications is < 1%, and morbidity is approximately 10 to 20%.2 Factors that indicate high risk are requirement for mechanical ventilation, reduced lung compliance, extreme hypoxia, pulmonary hypertension, immunosuppression, and risk of hemorrhage.1345 The highest risk (50% mortality) appears to be in ventilator-dependent patents.3 In a large series4 of patients undergoing VATS for a variety of indications, prolong air leak (> 5 days) occurred in 21% if the FEV1 was < 1 L, compared to 2% for those with better lung function. In the same report, patients > 75 years old had more air leaks than younger patients, but multivariate analysis was not performed.4 Rates of infection are low,6 but self-reported postoperative pain occurs in approximately 25% at 3 months and 15% at 1 year.7 Conventional wisdom maintains that VATS has advantages over open-lung biopsy,2 but the only randomized trial comparing the two approaches showed similar safety and efficacy.8 Open-lung biopsy, however, is preferred for patients with extreme hypoxia, prior pleural disease, pulmonary hypertension, or for those who require high airway pressures or are at greater risk of hemorrhage.2 If these risk factors are excluded and supplemental oxygen is not required, surgical lung biopsy for interstitial lung disease in ambulatory patients is considered such a low-risk procedure that several centers have begun performing the operation on outpatients.910
An article in the current issue of CHEST (see page 1600) by Lettieri et al and a previously published paper by Utz et al11 are sobering reports of the risks of surgical lung biopsy in patients with IPF who are receiving mechanical ventilation or who have rapid deterioration of respiratory status prior to surgery. These articles report overall 30-day mortality rates of 7% and 17%, respectively, following surgical lung biopsy in patients with IPF.11 However, if patients at high risk were excluded, mortality was approximately 1%, similar to that found in low-risk ambulatory patients with IPF who underwent lung biopsies reported by Hunninghake et al.12 Closer examination of these studies is instructive in pointing out the risks of biopsy in patients with rapidly progressive interstitial lung disease or those requiring mechanical ventilation.
Lettieri et al retrospectively collected 83 inpatients and outpatients, 88% of whom had an IIP as the final pathologic diagnosis. No patients were HIV positive or were receiving corticosteroids or chemotherapy. Mortality (three deaths in IPF patients at 30 days) was greater in patients requiring mechanical ventilation at the time of surgery or in those who were immunosuppressed (the type of immunosuppression was not specified). Age, requirement for supplemental oxygen, and severity of pulmonary function impairment did not affect outcome. The authors concluded that patients with IPF tolerate surgical lung biopsy well, but those who are ventilator dependent or are immunosuppressed are at higher risk of surgical lung biopsy.
Utz and colleagues11 of the Mayo Clinic reported a 30 day mortality of 17% after surgical lung biopsy in 60 patients who had the diagnosis of usual interstitial pneumonia (UIP)/IPF or UIP associated with connective tissue diseases. Of note, this small series11 represented only a fraction of patients with UIP seen at the Mayo Clinic, and lung biopsies and thoracic CT scans were performed infrequently for the evaluation of IPF at the time of the study. Many of the 10 patients who died had an accelerated decline in respiratory status at the time the lung biopsy was done. Results of a more recent and larger series12 from the same institution showed a much lower mortality rate in patients with interstitial lung disease following lung biopsies.
Caution is needed in interpreting the studies of Lettieri et al and Utz et al.11 The small number of deaths and potential sampling biases by including predominately sicker patients may have contributed the higher reported mortality rates. It is reassuring that when the high-risk patients were excluded from these two studies, the mortality rates were acceptably low. Multivariate analysis to define characteristics that predict increased risk is required on a larger population undergoing surgery. One large database that could be utilized, for example, is that from the clinical trials of interferon 
-1b in IPF.13
In the absence of more precise data for determining which patients with IPF are at greater risk of surgical lung biopsy, clinicians have to apply reasoned judgment to each patient by weighing the potential for harm against possible gain. The first decision is whether a surgical biopsy is necessary as dictated by the certainty of the diagnosis of IPF using radiographic and clinical criteria.1 The second decision concerns the risk of the contemplated biopsy. Based on available information, elements that indicate high risk include mechanical ventilation, marked impairment of lung function (FEV1 < 1 L), coagulopathy, immunosuppression, pulmonary hypertension, and severe hypoxia. A rapid deterioration of underlying lung disease can probably be added to this list based on the observations of Lettieri et al and Utz et al.11
References
-1b in patients with idiopathic pulmonary fibrosis. N Engl J Med 2004;350,125-133This article has been cited by other articles:
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  C. K. Katikireddy, G. Krishna, G. Berry, J. Faul, and W. Kuschner A 24-Year-Old Woman With Bilateral Pulmonary Infiltrates, Pericardial Effusion, and Bilateral Pleural Effusions Chest, December 1, 2005; 128(6): 4013 - 4017. [Full Text] [PDF]
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