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Southwest Pulmonary and Critical Care Fellowships

Pulmonary Journal Club

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

May 2017 Phoenix Pulmonary/Critical Care Journal Club
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
   Screening
November 2013 Tucson Pulmonary Journal Club: Macitentan
November 2013 Phoenix Pulmonary Journal Club: Pleural Catheter
   Infection
October 2013 Tucson Pulmonary Journal Club: Tiotropium Respimat 
October 2013 Pulmonary Journal Club: Pulmonary Artery
   Hypertension
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
June 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

 

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

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Entries in idiopathic pulmonary fibrosis (3)

Wednesday
Oct292014

June 2014 Tucson Pulmonary Journal Club: Pirfenidone in Idiopathic Pulmonary Fibrosis

King TE, Bradford WZ, Castro-Bernardini S, et al. ASCEND Study Group. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. New Engl J Med. 2014;370(22), 2083-92. [CrossRef] [PubMed]

Idiopathic pulmonary fibrosis is a chronic, progressive, and fatal lung disease that is characterized by irreversible loss of lung function. The 5-year survival rate that is similar to the rates for several cancers (1).

In the 2011, the official ATS/ERS/JRS/ALAT statement regarding idiopathic pulmonary fibrosis underlined that the preponderance of evidence to date suggests that pharmacologic therapy for IPF is without definitive, proven benefit (2). The committee made recommendations of varying strength against most therapies.

Pirfenidone is a pyridone compound with anti-inflammatory, antifibrotic, and antioxidant properties, with antagonism of Transforming Growth Factor (TGF)-  B1 effects. Pirfenidone inhibits fibroblast proliferation and collagen synthesis and reduce cellular and histological markers of fibrosis in animal models of lung fibrosis.

Three previous phase 3 randomized, double-blind, placebo-controlled, that examined pirfenidone for idiopathic pulmonary fibrosis had varying results (3,4). That led to the approval of pirfenidone for idiopathic pulmonary fibrosis by many governing bodies worldwide but not by the US Food and Drug Administration. This prompted US regulatory authorities to request an additional trial to support the approval of pirfenidone.

The Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND) is the fourth in a series of randomized, double blind, placebo-controlled trials. Pirfenidone was compared with placebo in patients with idiopathic pulmonary fibrosis. The study was conducted at 127 sites in 9 countries. Eligible patients were between the ages of 40 and 80 years and had received a centrally confirmed diagnosis of idiopathic pulmonary fibrosis. Patients were recruited July 2011 through January 2013. A total of 555 patients were enrolled; 278 were assigned to receive pirfenidone, and 277 were assigned to receive placebo. Physical examination and clinical laboratory assessments were performed at baseline and at weeks 2, 4, 8, 13, 26, 39, and 52. Pulmonary function, exercise tolerance, and dyspnea were assessed at baseline and at weeks 13, 26, 39, and 52.

The major inclusion criteria were having clinical symptoms consistent with IPF of 12 months duration; diagnosis of IPF, defined as the first instance in which a patient was informed of having IPF, at least 6 months and no more than 48 months before randomization; age 40 through 80 years, inclusive, at randomization; diagnosis of UIP or IPF by High resolution CT or surgical lung biopsy.

Major exclusion criteria included end stage renal disease, obstructive lung disease, congestive heart failure, end stage liver disease, arrhythmias and recent IPF exacerbations.

The primary outcomes of the study were to confirm the treatment effect of pirfenidone 2403 mg/d compared with placebo on change in percent predicted forced vital capacity (%FVC) in patients with idiopathic pulmonary fibrosis (IPF) and confirm the safety of treatment with Pirfenidone 2403 mg/d compared with placebo in patients with IPF.

In this randomized, controlled trial, the use of pirfenidone in patients with idiopathic pulmonary fibrosis led to a slower rate of loss in forced vital capacity than the use of placebo. Pirfenidone, as compared with placebo, reduced disease progression, as reflected by lung function, exercise tolerance, and progression-free survival, in patients with idiopathic pulmonary fibrosis. Treatment was associated with an acceptable side-effect profile and fewer deaths.

The major strengths of the include the randomized double-blinded control study design, straightforward hypothesis, minimal drop out rates, similarity to previous studies, however with a larger sample size and more central confirmation of diagnosis.

The study offers “New Hope for Idiopathic Pulmonary Fibrosis” (5).  Major concerns would be extrapolating findings to treat patient populations that were not assessed in this study. That includes patients with more severe disease; other interstitial lung disease, and patients with comorbidities that were excluded in this study. The study also doesn't assess if the effects are durable beyond 1 year.

Mohammed Alzoubaidi MBBS and Kenneth S. Knox MD

University of Arizona

Tucson, Arizona

References

  1. Nicholson AG, Colby TV, Dubois RM, Hansell DM, Wells AU. The prognostic significance of the histologic pattern of interstitial pneumonia in patients presenting with the clinical entity of cryptogenic fibrosing alveolitis. Am J Respir Crit Care Med. 2000;162(6):2213-7. [CrossRef] [PubMed]
  2. Raghu G, Collard HR, Egan JJ, et al. ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788-824. [CrossRef] [PubMed]
  3. Noble PW, Albera C, Bradford WZ, et al. CAPACITY Study Group. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet. 2011;377(9779):1760-9. [CrossRef] [PubMed]
  4. Taniguchi H, Ebina M, Kondoh Y, et al. Pirfenidone Clinical Study Group in Japan. (2010). Pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J. 2010;35(4):821-9. [CrossRef] [PubMed]
  5. Hunninghake GM. A new hope for idiopathic pulmonary fibrosis. New Engl J Med. 2014:,370(22), 214-3. [CrossRef] [PubMed]

Reference as: Alzoubaidi M, Knox KS. June 2014 Tucson pulmonary journal club: pirfenidone in idiopathic pulmonary fibrosis. Southwest J Pulm Crit Care. 2014;9(4):244-6. doi: http://dx.doi.org/10.13175/swjpcc142-14 PDF

Sunday
Jun082014

June 2014 Phoenix Pulmonary Journal Club: New Therapies for IPF and EBUS in Sarcoidosis

Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, Cottin V, Flaherty KR, Hansell DM, Inoue Y, Kim DS, Kolb M, Nicholson AG, Noble PW, Selman M, Taniguchi H, Brun M, Le Maulf F, Girard M, Stowasser S, Schlenker-Herceg R, Disse B, Collard HR; INPULSIS Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2071-82. [CrossRef] [PubMed]

Nintedanib is a tyrosine kinase inhibitor that has been shown to decrease the decline of FVC in phase 2 trials of idiopathic pulmonary fibrosis (IPF). This study was a phase 3 trial in which 2 replicate trials comparing nintedanib 150 mg twice daily to placebo. The trials were randomized double blind placebo controlled performed over 205 sites in 24 countries. Inclusion criteria were an age > 40, FVC > 50% and DLCO 30-79%. Patients were excluded if on prednisone > 15 mg/day or any other treatment for IPF. Patients were followed for 52 weeks and underwent spirometry at weeks 2, 4, 6, 12, 36 and 52. The primary endpoint was decline in FVC and the secondary endpoint was exacerbations of IPF. The results of the 2 trials showed the treatment groups had a 1 year decline in FVC of 114.7 and 113.6 verses 239ml and 207ml in the placebo groups. There was a decrease in acute exacerbations in the Inpulsis 2 group while there was an increase in the time to 1st exacerbation in the Inpulsis 1 group. The most common side effect was diarrhea, which resulted in treatment cessation in 25 patients. The trial was well done and hit its primary endpoint. A near 50% preservation of FVC at 1 year is impressive and additional longitudinal studies are needed to see if the effects are sustained. A dose adjustment may be needed to help correct the effect of diarrhea and further studies looking at the effect of dose on FVC decline will also be needed.

King TE Jr, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, Gorina E, Hopkins PM, Kardatzke D, Lancaster L, Lederer DJ, Nathan SD, Pereira CA, Sahn SA, Sussman R, Swigris JJ, Noble PW; ASCEND Study Group. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2083-92. [CrossRef] [PubMed]

Pirfenidone has been a promising agent in the fight against IPF. Prior studies showed conflicting results on the medications efficacy in preserving lung function, specifically forced vital capacity (FVC). This phase 3 clinical trial was performed over 127 sites within 9 countries. 555 patients with either biopsy proven or radiographically proven IPF were randomized to receive placebo (277 pts) or 2403 mg of pirfenidone (278 pts) daily for 52 weeks. Inclusion criteria were a diagnosis of IPF, FVC > 50%, DLCO > 30%, FEV1 > 80% and a 6 minute walk > 150 meters. The primary outcome was the change in FVC at week 52. Secondary outcomes were 6 minute walk distance, dyspnea, progression free survival and death. The results showed that patients taking pirfenidone had 50% less decline in an FVC of > 10% and > 50% of patients had no loss of lung function. The pirfenidone group also had fewer patients with a loss of 50m or more in their 6 minute walk test. The medication was well tolerated with the main side effects being cough, nausea, headache and diarrhea.

It appears that pirfenidone will be the first drug approved specifically for the treatment of IPF. It has already been approved in Europe and it remains to be seen if the results seen in this trial are sustainable in more long term studies.

von Bartheld MB, Dekkers OM, Szlubowski A, Eberhardt R, Herth FJ, in 't Veen JC, de Jong YP, van der Heijden EH, Tournoy KG, Claussen M, van den Blink B, Shah PL, Zoumot Z, Clementsen P, Porsbjerg C, Mauad T, Bernardi FD, van Zwet EW, Rabe KF, Annema JT. Endosonography vs conventional bronchoscopy for the diagnosis of sarcoidosis: the GRANULOMA randomized clinical trial. JAMA. 2013;309(23):2457-64. [CrossRef] [PubMed]

Sarcoidosis is a granulomatous inflammatory condition with multisystem involvement. In 90% of cases the disease involves the lungs, mediastinal and hilar lymph nodes. Definitive diagnosis is obtained by histology obtained through either transbronchial needle aspiration of hilar or mediastinal lymph nodes, transbronchial parenchymal lung biopsy or cervical mediastinoscopy. Transbronchial lung biopsies have shown a sensitivity of 60% with risk of hemorrhage and pneumothorax in up to 6%. Endobronchial (EBUS) or endoscopic esophageal ultrasound (EUS) guided lymph node biopsy have been shown to increase sensitivity to 80% with less than a 1% risk of pneumothorax and hemorrhage. This study compared transbronchial lung biopsy and EUS/BUS in diagnosing sarcoidosis. The study was a randomized control trial done in 14 centers within 6 countries and included 304 patients. 149 patients underwent conventional bronchoscopic evaluation while 155 patients underwent EBUS/EUS evaluation. Bronchoscopic evaluation included bronchoalveolar lavage (BAL) CD4/CD8 ratios, at least 4 transbronchial lung biopsies and 4 endobronchial mucosal biopsy samples. Of note, fluoroscopy was only used in 39% of cases. In the endosonography group, EUS or EBUS was performed . The decision to perform an esophageal or endobronchial procedure was left to investigator. The results showed that EUS or EBUS identified granulomas in 74% of patients compared to 48% in the transbronchial group. It must be pointed out that the greatest yield was seen in with esophageal aspiration of subcarinal lymph nodes and that blind transbronchial needle aspiration of lymph nodes were not performed in the bronchoscopic group. The study had several limitations that deviates from standard practices. In our institution it is rare that a blind transbronchial needle biopsy of an accessible subcarinal node is not performed, in addition, fluoroscopy is routinely used in all parenchymal lung biopsies. Although the study did show that EBUS/EUS is superior to transbronchial lung biopsies and BAL, a study looking at blind transbronchial lymph node biopsies versus EBUS/EUS would have been more valid. However after performing EBUS it will be hard to dispute that direct real time lymph node visualization in conjunction with on-site cytology is now the standard of care in the diagnosis of Sarcoid with lymph node involvement.

Manoj Mathew, MD FCCP MCCM

Reference as: Mathew M. June 2014 Phoenix pulmonary journal club: new therapies for IPF and EBUS for sardoidosis. Southwest J Pulm Crit Care. 2014;8(6):340-2. doi: http://dx.doi.org/10.13175/swjpcc078-14 PDF

Thursday
Mar152012

February 2012 Pulmonary Journal Club

Lee JS, Ryu JH, Elicker BM, Lydell CP, Jones KD, Wolters PJ, King TE Jr, Collard HR. Gastroesophageal reflux therapy is associated with longer survival in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2011;184:1390-4. (Click here for the abstract)

The relationship between gastroesophageal reflux disease (GERD) and idiopathic pulmonary fibrosis (IPF) remains a mystery. Although there is little contestation that the two entities often coexist, the cause and effect nature of GERD causing IPF remains unproven. The prevalence of GERD in IPF has been reported to be in the range of 67-88%. This study looks to see if treating this highly prevalent condition (GERD) impacts disease progression and mortality in patents with IPF.

This study was a prospective cohort study done at 2 institutions between 2001 and 2008. Patients with IPF were diagnosed based on radiographic and or histopathologic criteria. The presence of GERD was identified based on symptoms, uses of GERD medications or prior history of Nissen Fundoplication.

A total of 204 patients participated in the study. The results showed that the presence of GERD, treatment of GERD and history of Nissen Fundoplication were all associated with longer survival times when compared to patients with IPF and no GERD diagnosis. The strength of the study was that it reinforced prior studies that demonstrated that GERD treatment is beneficial in stabilizing IPF progression. The study was limited by its lack of randomization, blinding, and inclusion of smokers in the study group especially since cigarette smoking has been shown to be a risk factor in the development and progression of IPF.

This study reinforces that the prevalence of GERD in IPF is high. It further validates the benefit of treating GERD in patients with IPF. It still remains unclear as to whether GERD serves as a causal factor in the development of IPF. Of note, this study showed that patients with untreated GERD had improved survival (896 days) when compared to patients with IPF and no GERD symptoms (941days). The rationalization of this remains unclear, especially if we are to believe that GERD is a causal factor.  Our review of the study yielded us to concede that treating GERD in patients with IPF is likely to be beneficial and that further randomized controlled trials looking into the causal nature of GERD in IPF need to be done.

Manoj Mathew, MD FCCP, MCCM

Associate Editor, Pulmonary Journal Club

Reference as: Mathew M. February 2012 pulmonary journal club. Southwest J Pulm Crit Care 2012;4:57. (Click here for a PDF version of the journal club)