Transbronchial cryobiopsy, updated guidelines for chronic cough in children, PD-1 inhibition

Pulmonary Physiology, Function, and Rehabilitation

Functional imaging of the lung

Quantifying heterogeneity of ventilation and gas exchange in lung diseases remains a clinical challenge. Conventional pulmonary function test is insensitive to regional changes. The multiple inert gas elimination technique can quantify ventilation-perfusion distribution, but it requires invasive instrumentation (eg, pulmonary artery catheterization) and is not practical for clinical use. Computed tomography (CT) scans delineate spatial changes in lung structures but do not directly measure changes in ventilation and gas exchange. With its radiation, it is difficult to apply CT scanning repeatedly in patients. More recently, MR imaging techniques have been developed to directly “visualize” and quantify regional lung function (Kruger SJ, et al. J Magn Reson Imaging. 2016;43(2):295; Roos JE, et al. Magn Reson Imaging Clin N Am. 2015;23(2):217). These techniques employ inhalation of gases, such as oxygen, perfluorinated gases, and hyperpolarized ³He and ¹²⁹Xe. Hyperpolarized ³He has been studied the most; however, the dwindling supply of ³He gas and its rising cost have prevented its further development. ¹²⁹Xe has abundant supply and has emerged to be the inert gas of choice for MR imaging. Hyperpolarized ¹²⁹Xe can measure ventilation, like hyperpolarized ³He. In addition, Xe diffuses into alveolar barrier (interstitium and plasma) and red blood cells, where it exhibits distinct resonant frequency shifts that can be captured by MR. Therefore, in one test, information on pulmonary ventilation and gas transfer can be obtained. To date, the results from MR imaging studies have provided new insights into the pathophysiology of obstructive and restrictive lung diseases. With continuous development, MR imaging of the lung could become a clinically useful tool in the near future.

Yuh-Chin T. Huang, MD, MHS, FCCP
Steering Committee Member

Thoracic Oncology

Immune-mediated pneumonitis and PD-1 inhibition

Inhibitors of the programmed cell death 1 receptor (PD-1) have shown significant promise in the treatment of advanced stage malignancy. With the recent expansion of indications for use of these agents, the number of patients treated will continue to grow. Clinicians must be aware of their potential for serious adverse side effects, including dermatitis, colitis, and potentially life-threatening pneumonitis.

The development of pneumonitis secondary to PD-1 inhibitions is reported to occur in 2% to 5% of patients and can present at any time during therapy, with 1% of patients developing grade 3 or higher pneumonitis.^1,2 The most common symptoms are dyspnea and cough, though one-third of patients are asymptomatic at presentation.² Radiographic and pathologic features vary greatly and include organizing pneumonia, interstitial pneumonitis, hypersensitivity pneumonitis, or diffuse alveolar damage.³ While pneumonitis due to PD-1 inhibition is reportedly uncommon, the increasing number of patients expected to receive these medications will predictably result in increasing overall frequency of pneumonitis cases. In addition, the lack of large prospective randomized trials and reliance on radiographic rather than pathologic data in diagnosing immune-mediated pneumonitis gives one pause. Given the variability of presentation, lack of routine pathologic data, and increasing use of dual agents (eg, PD-1 and CTLA-4), chest physicians and medical oncologists should have a high index of suspicion yet practice equipoise in patients receiving immunotherapy who develop unexplained pulmonary symptoms or infiltrates. More research is needed to help improve the multidisciplinary diagnosis and treatment of this potentially serious complication.

David Maurice Chambers, MD
Fellow-in-Training Member

Jason Atticus Akulian, MD, MPH
Steering Committee Member

References

1. Nishino M, et al. Incidence of programmed cell death 1 inhibitor-related pneumonitis in patients with advanced cancer: a systematic review and meta-analysis. JAMA Oncology. 2016;2(12):1607.

2. Naidoo J, et al. Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy. J Clin Oncol. 2017;35(7):709.

3. Nishino M, et al. PD-1 inhibitor-related pneumonitis in advanced cancer patients: radiographic patterns and clinical course. Clin Cancer Res. 2016;22(24):6051.

Pulmonary Vascular Disease

Pulmonary Arterial Hypertension Associated With SLE

While pulmonary arterial hypertension (PAH) commonly complicates scleroderma (SSc), it is a rare complication of other connective tissue diseases (CTD), such as systemic lupus erythematosus (SLE). In the few prospective studies that utilize right-sided heart catheterization (RHC), the estimated prevalence of PAH in SLE is about 4%. However, since the prevalence of SLE is 10 to 15 times greater than SSc in the United States, the true prevalence of SLE-PAH may be higher than previously thought, and, thus, clinically relevant. Despite this, little is known about SLE-PAH.

A recent retrospective study from the French Pulmonary Hypertension Registry has added significantly to our understanding of this complication of SLE. Hachulla and colleagues studied 51 patients with RHC-proven SLE-PAH compared with 101 SLE control subjects without PAH. While the authors did not find any relevant differences in the demographics between groups, they did find a significantly higher prevalence of SSA and SSB antibodies in SLE-PAH. Interestingly, the presence of anti-U1 RNP antibody appeared to be less common in SLE-PAH patients; this lack of association is in contrast to prior studies in mixed CTD patients with anti-U1 RNP antibodies in which the prevalence of PAH can be as high as 60%. Further, none of the SLE-PAH patients demonstrated an acute response to vasodilator challenge during RHC, emphasizing that this maneuver does not need to be performed in SLE patients at risk of PAH. Trends toward improved survival in SLE-PAH patients treated with hydroxychloroquine are preliminary and hypothesis-generating but require confirmation in larger clinical studies.

Stephen Mathai, MD, FCCP
Chair

Leena Palwar, MD
Fellow-in-Training Member