Pulmonary Journal Club

Last 50 Pulmonary Journal Clubs

(Click on title to be directed to posting, most recent listed first)

October 2015 Phoenix Pulmonary Journal Club: Lung Volume Reduction
September 2015 Tucson Pulmonary Journal Club: Genomic Classifier for 
   Lung Cancer
April 2015 Phoenix Pulmonary Journal Club: Endo-Bronchial Ultrasound in
   Diagnosing Tuberculosis
February 2015 Tucson Pulmonary Journal Club: Fibrinolysis for PE
January 2015 Tucson Pulmonary Journal Club: Withdrawal of Inhaled
   Glucocorticoids in COPD
January 2015 Phoenix Pulmonary Journal Club: Noninvasive Ventilation In 
   Acute Respiratory Failure
September 2014 Tucson Pulmonary Journal Club: PANTHEON Study
June 2014 Tucson Pulmonary Journal Club: Pirfenidone in Idiopathic
   Pulmonary Fibrosis
September 2014 Phoenix Pulmonary Journal Club: Inhaled Antibiotics
August 2014 Phoenix Pulmonary Journal Club: The Use of Macrolide
   Antibiotics in Chronic Respiratory Disease
June 2014 Phoenix Pulmonary Journal Club: New Therapies for IPF and 
   EBUS in Sarcoidosis
March 2014 Phoenix Pulmonary Journal Club: Palliative Care
February 2014 Phoenix Pulmonary Journal Club: Smoking Cessation
January 2014 Pulmonary Journal Club: Interventional Guidelines
December 2013 Tucson Pulmonary Journal Club: Hypothermia
December 2013 Phoenix Pulmonary Journal Club: Lung Cancer
November 2013 Tucson Pulmonary Journal Club: Macitentan
November 2013 Phoenix Pulmonary Journal Club: Pleural Catheter 
October 2013 Tucson Pulmonary Journal Club: Tiotropium Respimat 
October 2013 Pulmonary Journal Club: Pulmonary Artery 
September 2013 Pulmonary Journal Club: Riociguat; Pay the Doctor
August 2013 Pulmonary Journal Club: Pneumococcal Vaccine 
   Déjà Vu
July 2013 Pulmonary Journal Club
June 2013 Pulmonary Journal Club
May 2013 Pulmonary Journal Club
March 2013 Pulmonary Journal Club
February 2013 Pulmonary Journal Club
January 2013 Pulmonary Journal Club
December 2012 Pulmonary Journal Club
November 2012 Pulmonary Journal Club
October 2012 Pulmonary Journal Club
September 2012 Pulmonary Journal Club
August 2012 Pulmonary Journal Club
July 2012 Pulmonary Journal Club
June 2012 Pulmonary Journal Club
May 2012 Pulmonary Journal Club
April 2012 Pulmonary Journal Club
March 2012 Pulmonary Journal Club
February 2012 Pulmonary Journal Club
January 2012 Pulmonary Journal Club
December 2011 Pulmonary/Sleep Journal Club 
October, 2011 Pulmonary Journal Club
September, 2011 Pulmonary Journal Club
August, 2011 Pulmonary Journal Club
July, 2011 Pulmonary Journal Club
May, 2011 Pulmonary Journal Club
April, 2011 Pulmonary Journal Club
February 2011 Pulmonary Journal Club 
January 2011 Pulmonary Journal Club 
December 2010 Pulmonary Journal Club


For complete Pulmonary Journal Club listing click here.

Both the Phoenix Good Samaritan/VA and the Tucson University of Arizona fellows have a periodic pulmonary journal club in which current or classic pulmonary articles are reviewed and discussed. A brief summary is written of each discussion describing thearticle and the strengths and weaknesses of each article.



October 2015 Phoenix Pulmonary Journal Club: Lung Volume Reduction

The October 2015 pulmonary journal club focused on the review of older studies evaluating lung volume reduction surgery and how this has transitioned toward the development of non-surgical modes of lung volume reduction. The physiology behind dyspnea in chronic obstructive pulmonary disease (COPD) is a complex process. One of the proposed mechanisms has been hyperinflation associated with air trapping. In the mid 1990s studies by Cooper and Peterson (1) offered a promising approach in which lung volume reduction (LVR) could improve ventilatory mechanics and improve dyspnea. As the procedure gained more popularity, additional larger scale trials were performed to support its validity.

We reviewed 2 studies looking at lung volume reduction. The first was "The Effect of Lung Volume Reduction Surgery In Patients With Severe Emphysema” (2) . This was a smaller, randomized controlled trial (RCT) that looked at 2 groups of 24 patients. Once group received LVR while the other received medical therapy. The primary outcome was mortality at 6 months and change in FEV1. The study did not show any mortality benefit but showed there was an increase in FEV1 of 150 ml by 6 months in the surgical group whereas the medical group showed no improvement. We reviewed a larger subsequent study, “A Randomized Trial Comparing Lung Volume Reduction Surgery with Medical Therapy for Severe Emphysema”, a RCT that included 1218 patients divided into 2 groups of 608 pts (surgical) and 610 pts (medical) (3). The primary outcome was mortality at 2 years and exercise capacity. The results showed that there was no overall mortality benefit, but there was an overall increase in exercise capacity. A subgroup analysis showed that patients that had poor baseline exercise tolerance and upper lobe predominant emphysema did the best with lower mortality rate and increased exercise capacity. This study was useful in defining a subset of patients most likely to benefit from LVR surgery.

The cost, expertise and risk of complications associated with lung volume reduction surgery led to expanding the physiology of reducing lung volumes via nonsurgical approaches. The use of one way endobronchial valves in allowing air to leave bronchial segments to promote lung volume reduction via atelectasis has been explored for over a decade. Our group was involved in the earlier trials which evaluated efficacy and safety of endobronchial valves (4) . The results from our experience did not show that the endobronchial valves reduced lung volumes. 

A subsequent study, "A Randomized Study of Endobronchial Valves for Advanced Emphysema" was reviewed (5). This was a large RCT that divided a total of 321 pts in a 2:1 format to 2 groups of 220 patients that received endobronchial valves pts and 101 patients that received medical treatment. The primary outcome was change in FEV1 and distance in 6 minute walk test. The placement of endobronchial valves was via bronchoscopy was guided based on emphysema seen on CT of the chest. The large majority of valves were placed in either right upper lobe (52%) or left upper lobe (14%). The study did show a mild increase in FEV1 of 4.3% in the patients treated with endobronchial valves and also resulted in an increase in 6 min walk distance of 9.3 m. However, patients receiving the endobronchial valves also noted higher rates of hemoptysis and COPD exacerbations. The reason for less than optimal results has been explained by the persistence of hyperinflation through collateral ventilation.

The physiologic basis why lung volume reduction may work in COPD remains the same. The surgical resection of apical emphysematous regions may be of some benefit in patients with apical emphysema and decreased exercise tolerance. The role of volume reduction via use of endobronchial valves may become useful if subsequent studies show that collateral ventilation does not lead to persistent hyperinflation and the reduction n volumes shows a sustained increase in FEV1 and 6 min walk test.

Manoj Mathew, MD FCCP


  1. Cooper JD, Patterson GA. Lung volume reduction surgery for severe emphysema. Semin Thorac Cardiovasc Surg. 1996;8(1):52-60. [PubMed]
  2. Geddes D, Davies M, Koyama H, Hansell D, Pastorino U, Pepper J, Agent P, Cullinan P, MacNeill SJ, Goldstraw P. Effect of lung-volume-reduction surgery in patients with severe emphysema. N Engl J Med. 2000;343(4):239-45. [CrossRef] [PubMed]
  3. Fishman A, Martinez F, Naunheim K, Piantadosi S, Wise R, Ries A, Weinmann G, Wood DE; National Emphysema Treatment Trial Research Group. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med. 2003;348(21):2059-73. [CrossRef] [PubMed]
  4. Shah PL, Slebos DJ, Cardoso PF, Cetti E, Voelker K, Levine B, Russell ME, Goldin J, Brown M, Cooper JD, Sybrecht GW; EASE trial study group. Bronchoscopic lung-volume reduction with Exhale airway stents for emphysema (EASE trial): randomised, sham-controlled, multicentre trial. Lancet. 2011;378(9795):997-1005. [CrossRef] [PubMed]
  5. Sciurba FC, Ernst A, Herth FJ, Strange C, Criner GJ, Marquette CH, Kovitz KL, Chiacchierini RP, Goldin J, McLennan G; VENT Study Research Group. A randomized study of endobronchial valves for advanced emphysema. N Engl J Med. 2010 Sep 23;363(13):1233-44. [CrossRef] [PubMed] 

Cite as: Mathew M. October 2015 Phoenix pulmonary journal club: lung volume reduction. Southwest J Pulm Crit Care. 2015;11(5):215-6. doi: http://dx.doi.org/10.13175/swjpcc138-15 PDF


September 2015 Tucson Pulmonary Journal Club: Genomic Classifier for Lung Cancer

Silvestri GA, Vachani A, Whitney D, et al. A bronchial genomic classifier for the diagnostic evaluation of lung cancer. N Engl J Med. 2015;373(3):243-51. [CrossRef] [PubMed]

Pulmonary lesions are a common diagnostic dilemma for clinicians. Current literature describes the sensitivity of bronchoscopic techniques to be between 34 and 88%; which varies significantly depending on size and location of the biopsied lesion (1). Previously described gene expression patterns have been found to be associated with malignancy in healthy epithelial cells of the proximal airways\(2). The primary aim of this study was to prospectively validate a specific gene expression classifier in patients undergoing bronchoscopic biopsy for suspected lung cancer.

The study involved two independent, prospective, multicenter, observational studies (AEGIS-1 and AEGIS-2) conducted in the U.S., Canada and Ireland at 28 sites. Patients were excluded if they were never smokers, under age 21, or current cancer or former lung cancer patients. Patients were followed for 12 months after bronchoscopy or until a diagnosis was established. A wide array of bronchoscopic and surgical techniques were used to ultimately make a diagnosis. Prior to undergoing invasive diagnostic testing, the treating physician was asked to estimate the patient’s pre-test probability of cancer.

The overall prevalence of lung cancer in the two cohorts was 76.5%. Bronchoscopy alone had 74% sensitivity (95% CI, 68 to 79) in AEGIS-1 and 76% (CI 95%, 71 to 81) in AEGIS-2 with a combined specificity of 100%. When combining the gene classifier with bronchoscopy, the sensitivity increased to 96% (95% CI, 93 to 98) in AEGIS-1 and 98% (95% CI, 96 to 99) in AEGIS-2 with a combined specificity of 47.9%.

The poor specificity of the gene classifier limits its clinical utility as an adjunct to bronchoscopy. Although the sensitivity was high, the low specificity makes this additional test of low diagnostic value for definitively ruling in cancer. When bronchoscopy was negative, the prevalence of lung cancer remained high, approximately 45%, and the resulting post-test probability of a positive gene-classifier test was 58% and the post-test probability of a negative test was 16%. Neither value is sufficiently predictive to avoid further invasive testing to definitely determine the presence or absence of cancer in this intermediate risk population. The racial composition of study participants was predominately white with a majority being males.  The age range of study participants was between 55 and 71. Because of that, the generalizability is more limited.  However, the gene classifier might have limited clinical utility for patients who are poor candidates for additional invasive testing.  A positive result might tilt the balance in favor of additional testing whereas a negative result might warrant watchful waiting. Overall, this dual approach to diagnostic assessment for lung nodules suspicious of being lung cancer is not ready for widespread implementation. 

Joshua Dill DO; Joe Gerald, MD, Ph.D.; Christian Bime MD, MSc and James Knepler MD.

University of Arizona

Tucson, Arizona USA


  1. Rivera MP, Mehta AC, Wahidi MM. Establishing the diagnosis of lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143:Suppl 5: e142S-e165S. [CrossRef] [PubMed]
  2. Spira A, Beane JE, Shah V, et al. Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer. Nat Med. 2007;13:361-6. [CrossRef] [PubMed] 

Cite as: Dill J, Gerald J, Bime C, Knepler J. September 2015 Tucson pulmonary journal club: genomic classifier for lung cancer. Southwest J Pulm Crit Care. 2015;11(3):119-20. doi: http://dx.doi.org/10.13175/swjpcc125-15 PDF


April 2015 Phoenix Pulmonary Journal Club: Endo-Bronchial Ultrasound in Diagnosing Tuberculosis

Lin SM, Chung FT, Huang CD, Liu WT, Kuo CH, Wang CH, Lee KY, Liu CY, Lin HC, Kuo HP. Diagnostic value of endobronchial ultrasonography for pulmonary tuberculosis. J Thorac Cardiovasc Surg. 2009;138(1):179-84. [CrossRef] [PubMed]

The diagnosis of tuberculosis in patients with inability to produce sputum or in patients that remain acid-fast bacilli (AFB) smear negative with high index of clinical suspicion remains a challenge and often results in treatment delay. This study examined the role in using endobronchial ultrasound (EBUS) to locate parenchymal infiltrates to allow for more accurate sampling of bronchial lavage fluid and transbronchial biopsies. The study examined 121 patients divided into 2 groups, 73 patients received EBUS guided bronchoscopy and 48 pts received conventional bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsies. It should be noted that patients undergoing transbronchial biopsies in the non-EBUS group appeared to have biopsies done without the use of fluoroscopy. The results showed that when EBUS was used to locate the parenchymal infiltrate the BAL smear was positive 31% vs 12% in non-EBUS patients and the transbronchial biopsies were positive in 24% vs 4.2% in non-EBUS. The study had several limitations as it did not utilize fluoroscopic guided biopsies or fluid sampling which would of likely increased the diagnostic yield in the non EBUS group. The study however does point out a seldom used approach to transbronchial biopsy by using EBUS to look for air bronchograms and tissue echogenicity. Perhaps utilizing EBUS in more centrally located infiltrates or nodules may offer a benefit over performing blind biopsies or biopsies in which fluoroscopy may be of limited view.

Geake J, Hammerschlag G, Nguyen P, Wallbridge P, Jenkin GA, Korman TM, Jennings B, Johnson DF, Irving LB, Farmer M, Daniel P. Steinfort DP. Utility of EBUS-TBNA for diagnosis of mediastinal tuberculous lymphadenitis: a multicentre Australian experience. J Thorac Dis 2015;7 (3):439-48. [CrossRef]

This was a retrospective study that evaluated the utility of EBUS guided mediastinal lymph node biopsy and culture in patients with suspected mediastinal tuberculosis. Mediastinal tuberculosis was based on clinical suspicion with no lung parenchymal lesions seen on CT scan. 159 patients received EBUS guided biopsy and culture. A total of 39 patients were diagnosed with mediastinal tuberculosis either based on culture (23 patients) or pathology showing granulomatous inflammation with negative cultures and response to tuberculosis treatment. 120 patients were negative for tuberculosis but did receive an alternative diagnosis. Alternative diagnosis of sarcoidosis (78 patients) and reactive lymphoid tissue (20 patients) were the most common alternative diagnosis. Although no mediastinoscopy was performed to confirm truly negative specimens, the presence of alternative diagnosis is reassuring that the combination of negative culture and pathology could results in the reported 98% negative predictive value. The study was limited by its design and smaller sample size, however using EBUS as a first line diagnostic modality makes sense as it may yield either the suspected or an alternative diagnosis in a large proportion of the cases.

Manoj Mathew MD, FCCP, MCCM

Banner University Good Samaritan Medical Center

Phoenix, AZ

Reference as: Mathew M. April 2015 Phoenix pulmonary journal club: endo-bronchial ultrasound in diagnosing tuberculosis. Southwest J Pulm Crit Care. 2015;10(4):197-8. doi: http://dx.doi.org/10.13175/swjpcc061-15 PDF


February 2015 Tucson Pulmonary Journal Club: Fibrinolysis for PE

Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370(15):1402-11. [CrossRef] [PubMed]

The role of fibrinolytic therapy among patients with intermediate-risk pulmonary embolism (PE) is controversial (1). When right ventricular dysfunction and myocardial injury are associated with PE, there is an increased risk of adverse events (2). However, the risk of bleeding with fibrinolytic therapy has previously been thought to outweigh the benefits among patients without overt hemodynamic collapse.

The Pulmonary Embolism Thrombolysis (PEITHO) trial was a multi-center, double-blind, placebo-controlled randomized trial designed to investigate the efficacy and safety of single-bolus injection with tenecteplase plus heparin anticoagulation versus heparin anticoagulation alone among normotensive patients with intermediate risk PE (3). The study included 1005 adult patients who were randomized within fifteen days of symptom onset; randomization occurred when both right ventricular dysfunction (echocardiography or spiral computed tomography) and myocardial injury (troponin I or T) were present. All patients were followed for 30 days. The primary outcome was death or hemodynamic collapse within 7 days of randomization. Safety outcomes included major extra cranial and intracranial hemorrhage within 7 days.

Fibrinolytic therapy was associated with less frequent hemodynamic collapse or death within 7 days of treatment (2.6% vs 5.6%, p=0.02). The result was primarily driven by fewer instances of hemodynamic collapse in tenecteplase group (1.6% vs 5.0%, p=0.002). At 30 days, there was no difference in mortality from any cause between the tenecteplase and usual care groups, 2.5% versus 3.2%, respectively (p=0.42). However, tenecteplase therapy was associated with higher risk of major bleeding and stroke than usual care, 11.5% versus 2.4% (p<0.001) and 2.4% versus 0.2% (p=0.003), respectively. Subgroup analysis showed a trend towards increased bleeding in patients older than 75 years though this was not significant (p=0.09).

PEITHO is a relatively large, expensive, randomized controlled trial that provides little guidance on the optimal care of patients with intermediate risk PE. While improvement in the composite outcome of death or hemodynamic decompensation was significant (Odds Ratio 0.44, CI95% 0.23-0.87), the benefit was primarily driven by less frequent hemodynamic compromise. Furthermore, any treatment benefit must be weighed against a substantially increased risk of major bleeding (Odds Ratio 5.55, CI95% 2.3-13.39) or stroke (Odds Ratio 12.10, CI95% 1.57-93.39). Given that follow-up is limited to 30 days and no patient-reported/patient-centered outcomes are available, it is difficult to provide patients or clinicians with the evidence they need to weigh the risks and benefits. Until better data are available, thrombolytic therapy for intermediate risk PE still remains weakly supported due to unclear efficacy and high risks of major bleeding or stroke, particularly among older patients.

Aarthi Ganesh MD, Christian Bime MD, and Joe Gerald PhD

University of Arizona

Tucson, AZ


  1. Konstantinides S, Goldhaber SZ. Pulmonary embolism: risk assessment and management. Eur Heart J. 2012;33:3014-22. [CrossRef] [PubMed]
  2. Konstantinides S. Acute pulmonary embolism. N Engl J Med. 2008;359:2804-13. [CrossRef] [PubMed]
  3. Meyer G, Vicaut E, Danays T, et al; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370(15):1402-11. [CrossRef] [PubMed] 

Reference as: Ganesh A, Bime C, Gerald J. February 2015 Tucson pulmonary journal club: fibrinolysis for PE. Southwest J Pulm Crit Care. 2015;10(2):97-8. doi: http://dx.doi.org/10.13175/swjpcc028-15 PDF


January 2015 Tucson Pulmonary Journal Club: Withdrawal of Inhaled Glucocorticoids in COPD

Magnussen H, Disse B, Rodriguez-Roisin R, et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med. 2014;371(14):1285-94. [CrossRef] [PubMed]

GOLD guidelines recommend various combinations of inhaled corticosteroids (ICS), long-acting beta-agonists (LABA), and long-acting muscarinic agonists (LAMA) to treat patients with chronic obstructive pulmonary disease (COPD) who are at high risk of exacerbation.  A substantial portion of patients are ultimately prescribed triple-therapy at some point. The WISDOM trial examined the risk of exacerbation among patients taking triple therapy who were subsequently weaned from their ICS treatment.

The present WISDOM trial was a randomized, double-blind, non-inferiority trial sponsored by Boehringer Ingelheim Pharma. Over 4 years, approximately 2500 participants in 23 non-US countries with severe or very severe COPD were randomized. Participants were eligible if they were >40 years of age, were current or former smokers with ≥10 pack-year history, and had at least one exacerbation within the year prior to screening. Numerous exclusion criteria included significant comorbidity, prior lung resection, asthma or bronchiectasis, chronic oxygen use, oral steroid requirement, recent exacerbation, respiratory tract infection, or pulmonary rehabilitation. The study had 90% power to evaluate a pre-specified non-inferiority margin of 1.20 for the upper limit of the 95% confidence interval for the hazard ratio.

All participants received an initial 6 week treatment with fluticasone 500 mcg BID, salmeterol 50 mcg BID, and tiotropium 18 mcg daily. Based on random assignment, participants either continued triple therapy or had their fluticasone withdrawn in a step-wise fashion. The primary outcome was the time to first moderate or severe COPD exacerbation during the 52 week study period. Eighty-three percent of participants were men, the overall mean age was 64 years, and the mean FEV1 was 0.93 liters (33% of predicted). Approximately 40% were receiving triple therapy prior to enrollment. Approximately 20% of participants did not complete the study.

The non-inferiority margin was confirmed with a hazard ratio of 1.06 (CI95% 0.94 - 1.19). The mean reduction in FEV1 for the ICS withdrawal group was 38 mL greater than the reduction for the control group at week 18, and this difference increased to 43 mL by the end of the study (p<0.001). The difference in the St. George’s Respiratory Questionnaire (SGRQ) score were statistically significant at week 52, an increase of 1.15 in the withdrawal group vs. decrease of 0.07 in the continuation group (p = 0.047). Adverse events did not differ among the two groups.

The results suggest that gradual withdrawal of ICS from a triple therapy regimen is not associated with a meaningfully increased risk of exacerbation among patients with moderate-to-severe COPD. However, there were statistically significant, but perhaps not clinically meaningful, deterioration in FEV1 and SGRQ scores. Strengths of this study included a large participant population, a year-long follow-up, and use of clinically relevant and patient-centered outcomes. While the study was conducted in many countries, most participants were white and male. The homogeneity of this group makes it difficult to generalize to other patient groups. Patients who had no exacerbations in the prior year (arguably the group most appropriate to step-down therapy) were not included. It also does not provide information on the safety of abrupt withdrawal of ICS. The long-term consequences of the small reductions in FEV1 and health status are uncertain. For patients intolerant to or reluctant to consider ICS treatment, dual LABA and LAMA treatment appears to yield clinically similar outcomes.

Candy Wong MD, Cristine Berry MD and Joe Gerald PhD

University of Arizona

Tucson, AZ

Reference as: Wong C, Berry C, Gerald J. January 2015 Tucson pulmonary journal club: withdrawal of inhaled glucocorticoids in COPD. Southwest J Pulm Crit Care. 2015;10(2):79-80. doi: http://dx.doi.org/10.13175/swjpcc019-15 PDF