January 2015 Arizona Thoracic Society Notes

Dr. Judd Tillinghast was presented a plaque in recognition of being chosen by his colleagues as the Arizona Thoracic Society Physician of the Year In 2014.  

Dr. Rajeev Saggar made a presentation entitled "Pulmonary fibrosis-associated pulmonary hypertension: a unique phenotype".  This presentation focused on new echocardiographic methods of assessing right ventricular (RV) function and the pathophysiology of RV dysfunction. Dr. Saggar presented data from a paper he authored on parenteral treprostinil in patients with idiopathic pulmonary fibrosis and pulmonary artery hypertension which was published in Thorax (1).

There were 2 case presentations, both from the Phoenix VA by Dr. Elijah Poulos:

1. A 65 year-old man presented with cough and chills.  His past medical history included multiple myeloma treated with chemotherapy, radiation therapy to spine and bone marrow transplant.  He had a prior vertebroplasty. His symptoms did not improve with doxycycline.  Computerized tomography angiography was done and showed areas of unusual abnormalities in lung that were very high density.  This was determined to be cement emboli from the prior vertebroplasty (pulmonary cement emboli, PCE) which has been previously reported as a complication of this procedure.  The appropriate treatment options in this case were discussed.
2. A 69 year-old man presented with dyspnea on exertion over past couple of years.  Chest radiography showed abnormal areas of central fibrosis with sparing of the lung periphery.  A thoracic CT scan also demonstrated central fibrotic/cystic changes.  The patient subsequently admitted to use of crack cocaine which started at age 59.  There are reports of similar pulmonary fibrosis associated with use of crack cocaine (2).  The possible pathophysiologic mechanisms were discussed.

The next meeting in Phoenix will be at Scottsdale Shea on Wednesday, March 25 at 6:30 PM.

Lewis J. Wesselius, MD

President, Arizona Thoracic Society

References

1. Saggar R, Khanna D, Vaidya A, et al. Changes in right heart haemodynamics and echocardiographic function in an advanced phenotype of pulmonary hypertension and right heart dysfunction associated with pulmonary fibrosis. Thorax. 2014;69(2):123-9. [CrossRef] [PubMed]
2. O'Donnell AE, Mappin FG, Sebo TJ, Tazelaar H. Interstitial pneumonitis associated with "crack" cocaine abuse. Chest. 1991;100(4):1155-7. [CrossRef] [PubMed] 

Reference as: Wesselius LJ. January 2015 Arizona thoracic society notes. Southwest J Pulm Crit Care. 2015;10(1):56. doi: http://dx.doi.org/10.13175/swjpcc012-15 PDF 

May 2014 Arizona Thoracic Society Notes

The May 2014 Arizona Thoracic Society meeting was held on Wednesday, 5/28/2014 at Scottsdale Shea Hospital beginning at 6:30 PM. There were 13 in attendance representing the pulmonary, critical care, sleep and radiology communities.

A discussion was held regarding the Arizona Thoracic Society relationship with the American Lung Association. Several members volunteered to talk to the lung association regarding common ground to strengthen the relationship.

The wine tasting with the California, New Mexico and Colorado Thoracic Societies at the American Thoracic Society International Meeting was a big success. There were about 55 at the meeting. The tasting will probably be held again next year.

At the ATS meeting data was presented that pirfenidone was effective in reducing the progression of idiopathic pulmonary fibrosis (IPF). The data was published in the New England Journal of Medicine on 8/29/14 (1). Lewis Wesselius is one of the investigators enrolling patients in a phase 3 trial while InterMune reapplies to the FDA for approval of pirfenidone in IPF.

Two cases were presented:

1. Lewis Wesselius from the Mayo Clinic Arizona presented a 53 year old woman with a chronic, nonproductive accompanied by malaise and a modest weight loss. She was treated for asthma without improvement.  She was a nonsmoker and had a SpO2 of 98% on room air. Her lungs were clear to auscultation.  Routine laboratory evaluation was unremarkable and exhaled nitric oxide was normal. Thoracic CT scan showed a subtle broncholitis. She was empirically treated for gastroesophageal reflux disease (GERD) without improvement. Bronchoalveolar lavage was performed and showed Nocardia asteroides. She had no evidence of immunocompromise. She was treated with sulfamethoxazole and trimethoprim which produced a rash and then minocycline for 4 months. Her cough resolved. However, when the minocycline was stopped her cough returned. She is currently receiving an additional course of minocycline planned for 6 months.
2. Suresh Uppalapu presented a 58 year old fireman with a complaint of dyspnea on exertion. He has a history of obstructive sleep apnea and lives at an elevation of 7000 feet. The patient had significant desaturation with exercise. Chest x-ray showed borderline cardiomegaly but was otherwise normal. Thoracic CT scan showed pulmonary artery enlargement and borderline right ventricular (RV) enlargement. Ultrasound of the hear showed an enlarged RV but it was difficult to measure PA pressure.  Right-sided heart catherization showed a mean pulmonary artery pressure of 35 cm H2O with a  step up in the oxygen saturation at the right atrium. Transesophageal echocardiogram (TEE) showed a patent foramen ovale (PFO).  Insertion of a balloon stopped the right to left shunting but resulted in a significant increase in the pulmonary artery pressure. He was referred for percutaneous closure of the PFO along with treatment of his pulmonary artery hypertension.

There being no further business the meeting was adjourned about 8:15 PM. The June meeting is scheduled for Tucson. There will be no meeting in July. The next meeting in Phoenix will be a case presentation conference on August 27, 6:30 PM at Scottsdale Shea Hospital.

Richard A. Robbins, MD

Reference

1. King TE Jr, Bradford WZ, Castro-Bernardini S, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med 2014;370:2083-92. [CrossRef] [PubMed] 

Reference as: Robbins RA. May 2014 Arizona thoracic society notes. Southwest J Pulm Crit Care. 2014;8(6): 297-8. doi: http://dx.doi.org/10.13175/swjpcc072-14 PDF

December 2013 Arizona Thoracic Society Notes

A breakfast meeting of the Arizona Thoracic Society and the Tucson winter lung series was held on Saturday, 12/14/2013 at Kiewit Auditorium on the University of Arizona Medical Center Campus beginning at 8:30 AM. There were 31 in attendance.

A lecture was presented by Joe G. N. "Skip" Garcia, MD, the senior vice president for health sciences at the University of Arizona (Figure 1).

Figure 1. Joe G. N. “Skip” Garcia, MD

The title of Garcia’s talk was “Personalizing Medicine in Cardiopulmonary Disorders: The Post ACA Landscape”.

Garcia began with reiterating that the Affordable Care Act (ACA, Obamacare) is fact and could pose a threat to academic medical centers. However, he views the ACA as an opportunity to develop personalized medicine which grew from the human genome project. Examples cited included the genetic variability among patients in determining the dose of warfarin and bronchodilator response to beta agonists in asthma (1,2).

Garcia’s laboratory has studied predominately 6 diseases including the adult respiratory distress syndrome (ARDS), idiopathic pulmonary fibrosis (IPF), sarcoidosis, asthma, pulmonary artery hypertension and sickle cell disease. Each has in common that there has been minimal progress made in the past generation and each has been shown to have racial or ethnic disparities in outcomes. He cited examples of how molecular testing could improve care.

Black and Hispanic patients with ARDS have a significantly higher risk of death compared with white patients (3). Garcia noted that the ventilator is not necessarily a friend and use of higher tidal volumes has been associated with increased mortality (4). He reasoned that the variation in susceptibility to ventilator induced lung injury could potentially explain the racial differences in mortality. Beginning with a dog model of ARDS, highly significant regional differences in gene expression were observed between lung apex/base regions. One of these potential targets was pre-B-cell colony enhancing factor (PBEF), a gene not previously associated with lung pathophysiology (5). Further work showed PBEF could induce changes seen in ARDS including a neutrophil alveolitis and increases in nuclear factor-κβ (NFKB) expression (6).

Few would question that there is a need for validated biomarkers in idiopathic pulmonary fibrosis. Using a similar approach to the investigation of PBEF in ARDS, peripheral blood mononuclear cell (PBMC) gene expression profiles predictive of poor outcomes in idiopathic pulmonary fibrosis (IPF) were examined by microarray. Microarray analyses suggest that 4 genes (CD28, ICOS, LCK, and ITK) are potential outcome biomarkers in IPF and should be further evaluated for patient prioritization for lung transplantation and stratification in drug studies (7). PBMC gene expression profiles were also examined in sarcoidosis.  There was a significant association of single nucleotide polymorphisms (SNPs) in signature genes with sarcoidosis susceptibility and severity (8). Further examples were presented on sickle cell disease.

Garcia concluded that molecular techniques represent powerful tools to investigate potential therapeutic approaches in respiratory diseases where little progress has been made.

Richard A. Robbins, MD

References

1. International Warfarin Pharmacogenetics Consortium, Klein TE, Altman RB, Eriksson N, Gage BF, Kimmel SE, Lee MT, Limdi NA, Page D, Roden DM, Wagner MJ, Caldwell MD, Johnson JA. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med. 2009;360(8):753-64. [CrossRef] [PubMed]
2. Duan QL, Lasky-Su J, Himes BE, Qiu W, Litonjua AA, Damask A, Lazarus R, Klanderman B, Irvin CG, Peters SP, Hanrahan JP, Lima JJ, Martinez FD, Mauger D, Chinchilli VM, Soto-Quiros M, Avila L, Celedón JC, Lange C, Weiss ST, Tantisira KG. A genome-wide association study of bronchodilator response in asthmatics. Pharmacogenomics J. 2013 Mar 19. [Epub ahead of print] [CrossRef] [PubMed]
3. Erickson SE, Shlipak MG, Martin GS, Wheeler AP, Ancukiewicz M, Matthay MA, Eisner MD; National Institutes of Health National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. Racial and ethnic disparities in mortality from acute lung injury. Crit Care Med. 2009 Jan;37(1):1-6. [CrossRef] [PubMed]
4. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1301-8. [CrossRef] [PubMed]
5. Simon BA, Easley RB, Grigoryev DN, Ma SF, Ye SQ, Lavoie T, Tuder RM, Garcia JG. Microarray analysis of regional cellular responses to local mechanical stress in acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2006;291(5):L851-61. Herazo-Maya JD, Noth I, Duncan SR, Kim S, Ma SF, Tseng GC, Feingold E, Juan-Guardela BM, Richards TJ, Lussier Y, Huang Y, Vij R, Lindell KO, Xue J, Gibson KF, Shapiro SD, Garcia JG, Kaminski N. Peripheral blood mononuclear cell gene expression profiles predict poor outcome in idiopathic pulmonary fibrosis. Sci Transl Med. 2013 Oct 2;5(205):205ra136.
6. Hong SB, Huang Y, Moreno-Vinasco L, Sammani S, Moitra J, Barnard JW, Ma SF, Mirzapoiazova T, Evenoski C, Reeves RR, Chiang ET, Lang GD, Husain AN, Dudek SM, Jacobson JR, Ye SQ, Lussier YA, Garcia JG. Essential role of pre-B-cell colony enhancing factor in ventilator-induced lung injury. Am J Respir Crit Care Med. 2008;178(6):605-17. [CrossRef] [PubMed]  
7. Zhou T, Zhang W, Sweiss NJ, Chen ES, Moller DR, Knox KS, Ma SF, Wade MS, Noth I, Machado RF, Garcia JG. Peripheral blood gene expression as a novel genomic biomarker in complicated sarcoidosis. PLoS One. 2012;7(9):e44818. [CrossRef] [PubMed] 

Reference as: Robbins RA. December 2013 Arizona thoracic society notes. Southwest J Pulm Crit Care. 2013;7(6):360-2. doi: http://dx.doi.org/10.13175/swjpcc175-13 PDF