Rade Tomic

Decreased Risk of Radiation Pneumonitis With Incidental Concurrent Use of Angiotensin-Converting Enzyme Inhibitors and Thoracic Radiation Therapy

PURPOSEnAngiotensin-converting enzyme (ACE) inhibitors have been shown to mitigate radiation-induced lung injury in preclinical models. The aim of this study was to evaluate whether ACE inhibitors decrease the risk of radiation pneumonitis in lung cancer patients receiving thoracic irradiation.nnnMETHODS AND MATERIALSnPatients with Stage I through III small-cell and non-small-cell lung cancer treated definitively with radiation from 2004-2009 at the Clement J. Zablocki Veterans Affairs Medical Center were retrospectively reviewed. Acute pulmonary toxicity was quantified within 6 months of completion of treatment according to the Common Terminology Criteria for Adverse Events version 4. The use of ACE inhibitors, nonsteroidal anti-inflammatory drugs, inhaled glucocorticosteroids, statins, and angiotensin receptor blockers; dose-volume histogram parameters; and patient factors were assessed for association with Grade 2 or higher pneumonitis.nnnRESULTSnA total of 162 patients met the criteria for inclusion. The majority of patients had Stage III disease (64%) and received concurrent chemotherapy (61%). Sixty-two patients were identified as ACE inhibitor users (38%). All patients had acceptable radiation plans based on dose-volume histogram constraints (V20 [volume of lung receiving at least 20 Gy] ≤37% and mean lung dose ≤20 Gy) with the exception of 2 patients who did not meet both criteria. Grade 2 or higher pulmonary toxicity occurred in 12 patients (7.4%). The rate of Grade 2 or higher pneumonitis was lower in ACE inhibitor users vs. nonusers (2% vs. 11%, p = 0.032). Rates of Grade 2 or higher pneumonitis were significantly increased in patients aged greater than 70 years (16% vs. 2%, p = 0.005) or in whom V5 (volume of lung receiving at least 5 Gy) was 50% or greater (13% vs. 4%, p = 0.04). V10 (volume of lung receiving at least 10 Gy), V20, V30 (volume of lung receiving at least 30 Gy), and mean lung dose were not independently associated with Grade 2 or higher pneumonitis.nnnCONCLUSIONnACE inhibitors may decrease the incidence of radiation pneumonitis in patients receiving thoracic radiation for lung cancer. These findings are consistent with preclinical evidence and should be prospectively evaluated.

Mitigation of Late Renal and Pulmonary Injury After Hematopoietic Stem Cell Transplantation

PURPOSEnTo update the results of a clinical trial that assessed whether the angiotensin-converting enzyme inhibitor captopril was effective in mitigating chronic renal failure and pulmonary-related mortality in subjects undergoing total body irradiation (TBI) in preparation for hematopoietic stem cell transplantation (HSCT).nnnMETHODS AND MATERIALSnUpdated records of the 55 subjects who were enrolled in this randomized controlled trial were analyzed. Twenty-eight patients received captopril, and 27 patients received placebo. Definitions of TBI-HSCT-related chronic renal failure (and relapse) were the same as those in the 2007 analysis. Pulmonary-related mortality was based on clinical or autopsy findings of pulmonary failure or infection as the primary cause of death. Follow-up data for overall and pulmonary-related mortality were supplemented by use of the National Death Index.nnnRESULTSnThe risk of TBI-HSCT-related chronic renal failure was lower in the captopril group (11% at 4 years) than in the placebo group (17% at 4 years), but this was not statistically significant (p > 0.2). Analysis of mortality was greatly extended by use of the National Death Index, and no patients were lost to follow-up for reasons other than death prior to 67 months. Patient survival was higher in the captopril group than in the placebo group, but this was not statistically significant (p > 0.2). The improvement in survival was influenced more by a decrease in pulmonary mortality (11% risk at 4 years in the captopril group vs. 26% in the placebo group, p = 0.15) than by a decrease in chronic renal failure. There was no adverse effect on relapse risk (p = 0.4).nnnCONCLUSIONSnCaptopril therapy produces no detectable adverse effects when given after TBI. Captopril therapy reduces overall and pulmonary-related mortality after radiation-based HSCT, and there is a trend toward mitigation of chronic renal failure.

C-reactive protein and copeptin : prognostic predictors in chronic obstructive pulmonary disease exacerbations

Purpose of review Acute exacerbation of chronic obstructive pulmonary disease (COPD) is a natural event in the course of COPD and remains a major cause of morbidity and mortality associated with this disease. Clinical criteria that define an acute exacerbation are subjective and open for debate. Identifying biomarkers that would be easily measured and followed in patients with acute exacerbation of COPD seems to be highly attractive. The aim of this review is to assess the role of biomarkers, C-reactive protein (CRP) and copeptin, as prognostic predictors in COPD exacerbations. Recent findings Many pulmonary biomarkers have been extensively studied in the recent years. CRP and copeptin have gained particular interest. Recent data suggest that CRP is elevated during an acute exacerbation of COPD but CRP alone is neither sensitive nor specific in predicting clinical severity or outcome. Copeptin increases during acute exacerbation of COPD and may correlate with disease severity. Summary Further studies are needed to determine the role of CRP and copeptin as biomarkers that aid in diagnosis and clinical outcome in acute exacerbation of COPD.

Cellular Inflammatory Infiltrate in Pneumonitis Induced by a Single Moderate Dose of Thoracic X Radiation in Rats

Abstract The goal of these studies was to characterize the infiltrating inflammatory cells during pneumonitis caused by moderate doses of radiation. Two groups of male rats (WAG/RijCmcr, 8 weeks old) were treated with single 10- or 15-Gy doses of thoracic X radiation; a third group of age-matched animals served as controls. Only 25% rats survived the 15-Gy dose. Bronchoalveolar lavage fluid and whole lung mounts were subjected to cytological and histological evaluation after 8 weeks for distribution of resident macrophages, neutrophils, lymphocytes and mast cells. There was a modest increase in airway and airspace-associated neutrophils in lungs from rats receiving 15 Gy. Mast cells (detected by immunohistochemistry for tryptase) increased over 70% with 10 Gy and over 13-fold after 15 Gy, with considerable leakage of tryptase into blood vessels and airways. Circulating levels of eight inflammatory cytokines were not altered after 10 Gy but appeared to decrease after 15 Gy. In summary, there were only modest increases in cellular inflammatory infiltrate during pneumonitis after a non-lethal dose of 10 Gy, but there was a dramatic rise in mast cell infiltration after 15 Gy, suggesting that circulating levels of mast cell products may be useful markers of severe pneumonitis.

Cryotechnology in diagnosing and treating lung diseases.

Cryotechnology has been used in treating lung cancer for many years, now it is emerging to have a new indication in diagnosing lung diseases. Cryoprobe transbronchial lung biopsy has been introduced into clinical practice as a new technique, providing a larger biopsy specimen, potentially improving the diagnostic yield of transbronchial biopsies in parenchymal lung diseases. Although recent small pilot studies suggest that cryotransbronchial lung biopsies are comparable to conventional transbronchial biopsies in terms of diagnostic yield and safety profile in lung transplant patients, cryoprobe transbronchial lung biopsy is still being evaluated and its role in clinical practice is not well defined. Cryotherapy has been proven as a safe and effective method to debulk endobronchial lesions, providing palliation for advanced central obstructive tumors. Its use and efficacy is also studied in direct cryosurgery and percutaneous application in lung cancer. Cryoprobes can also be used to extract foreign bodies from the airways by causing cryoadhesion. We aim to summarize the therapeutic and diagnostic application of cryotechnology in pulmonary diseases.

Cognitive function in idiopathic pulmonary fibrosis

The purpose of this study was to investigate whether there is evidence that individuals with severe idiopathic pulmonary fibrosis (IPF) have cognitive deficits when compared to individuals with healthy lungs. Participants completed five neuropsychological tests: Trail Making Test (TMT) A and B, Stroop Color Word Test (1, 2, 3), Hopkins Verbal Learning Test, Boston Naming Test, and Grooved Pegboard Test, additionally, the short form-36 and Beck Depression Index. Twelve participants (7 male, mean age 69.3, 9.4 years) comprised the severe IPF group defined by a diffusion capacity for carbon monoxide (DLCO) <30%. Thirty-four patients (22 male, mean age 63.2, 9.6 years) comprised the mild-to-moderate group with a DLCO >30%. Participating spouses (n = 15, 4 male) served as the control group and had a mean age of 66.0, 10.8 years. Controlling for gender and age, the severe group had a significantly longer mean TMT B time (69.4, 135.9 seconds) than the mild group and the control group (86.7 seconds vs 83.2 seconds; p = 0.004 and 0.008 respectively), suggesting inferior performance on tasks requiring speed divided attention. In addition, the severe group had a significantly lower number of correctly identified colors in the Stroop 3 test (22.4 vs 30.6 vs 38.6; p < 0.001), suggesting slower processing speeds when requiring suppression of a familiar response. Participants with severe IPF had worse cognitive function than mild IPF or control subjects. Further research is needed to explain these findings and to develop interventions tailored to address these deficits.

Chyloptysis causing plastic bronchitis

Chyloptysis is a rare clinical problem that is associated with conditions affecting lymphatic channels in the thorax. Diagnosis is usually made when the patients present with expectoration of milky-white sputum or of thick tenacious mucus in the shape of smaller bronchi (bronchial cast). Typically the symptoms resolve after coughing up of the bronchial casts. Pleural, mediastinal, pulmonary or lymphatic abnormalities result in chyloptysis. Lymphangiography and detection of lipids (cholesterol or triglycerides) in sputum help to establish the diagnosis. However, lymphangiography may not be positive in all patients. We report 2 patients with chyloptysis and bronchial casts with different etiologies. Abnormal lymphatics were demonstrated in one of our cases, but the second patients lymphangiogram was normal. In this patient we suspect that high venous filling pressures due to congestive heart failure had a causative effect in the setting of compromised lymphatic drainage in the thorax due to a prior history of radiation therapy to the chest for lymphoma.

Nontuberculous mycobacterial hypersensitivity pneumonitis related to a home shower: treatment and secondary prevention.

A 57-year-old physician with increasing dyspnoea and hypoxaemia had a high-resolution CT scan of the chest, which disclosed diffuse pulmonary ground glass opacities, more pronounced in the upper lobes with minimal mediastinal lymphadenopathy. Transbronchial biopsy of the right middle and lower lobes was performed, demonstrating varying degrees of well circumscribed organising granulomatous pneumonitis thought to be most consistent with hypersensitivity to nontuberculous mycobacteria. Cultures of water obtained from the patient’s home shower were positive for Mycobacterium avium complex. The patient began substituting baths for showers, experiencing some gradual improvement of his symptoms. Subsequently, he installed point-of-use 0.2 micron membrane filters on his shower, and resumed regular showering after installation with continued symptomatic improvement. CT scans at 3 and 18 months revealed improvement and resolution, respectively. Four years later, he continues to shower in filtered home shower water and remains clinically well.

Acute Exacerbation of Interstitial Lung Disease After Cryobiopsy

Cryotherapy has been used in treatment of lung cancer for decades. The utility of cryotechnology in diagnosis of lung diseases is emerging and gaining popularity. Cryobiopsy (CB) of the lung, when compared with conventional transbronchial forceps lung biopsy, has proposed to have a higher diagnostic yield in interstitial lung disease by providing larger biopsy specimen and less crush artifact. Acute exacerbation of interstitial lung disease (AEILD) has been well described with surgical lung biopsies and, rarely, with conventional transbronchial forceps biopsy. The incidence of AEILD after CB is not known. Here we are presenting a case of AEILD after CB.

Single Versus Bilateral Lung Transplantation for Idiopathic Pulmonary Fibrosis in the Lung Allocation Score Era

BACKGROUNDnIdiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease. Lung transplantation is the only therapy associated with prolonged survival. The ideal transplant procedure for IPF is unclear. Outcomes after single transplantation (SLTx) versus bilateral lung transplantation (BLTx) in IPF patients after introduction of the Lung Allocation Score were examined.nnnMETHODSnRecords of patients undergoing lung transplantation for IPF at our institution between May 2005 and March 2017 were reviewed to examine the effect of transplant laterality. Primary outcomes were overall, rejection-free, and bronchiolitis obliterans (BOS)-free survival at 1 and 5xa0years post-transplant.nnnRESULTSnLung transplantation was performed in 151 IPF patients post-Lung Allocation Score. Most recipients were male with average age 59xa0±xa08xa0years. SLTx was performed in 94 patients (62%). In the overall cohort, comparative survival between SLTx and BLTx was similar at 1 and 5xa0years before and after adjusting for age and pulmonary hypertension (PH). SLTx was associated with shorter ventilator time and intensive care unit stay and trended toward improved survival over BLTx in patients without PH.nnnCONCLUSIONSnThe use of SLTx versus BLTx in IPF did not correspond to significantly different survival adjusting for age and PH. BLTx was associated with prolonged postoperative ventilation and length of stay compared with SLTx. Patients without PH, all older patients, and patients with PH and advanced disease should be considered for SLTx for IPF.