Spontaneous Pneumothorax: Why Anger Management is Important

Paragonvet.comImaging.consult.comStudyhealth.comSPONTANEOUSPNEUMOTHORAX: WHYANGER MANAGEMENT ISMeddean.luc.eduIMPORTANTVicki Wilke, DVM, PhD, DACVS,Alycen Lundberg, Kristy Metivier, DVM, MS,http://www.glogster.com/media/1/4/21/16/4211699.jpgNicholas Robinson, BVSC, PhD, MACVSCVicki Wilke, DVM, PhD, DACVSNick Robinson, B.V.SC., PhD

Clinical Signs and Physical Exampetdoctors.co.ukdog-obedience-training-online.compets.webmd.comehow.comgimpydogblog.blogspot.comluluandchu.wordpress.comamandabout-town.blogspot.comiknow2.netnetwork.bestfriends.org

Radiographic Findingsvetstreamcanis.commypetslivewithavet.blogspot.comIncreased width of air-filled pleural spaceRetraction of lung margins (follow vascular patterns)Partial pulmonary collapseElevated cardiac silhouette (lateral view)Tension pneumothorax:mediastinal shiftflattening of diaphragm

Pulmonary Blebs vs. BullaePulmonary bleb (A), type 1bulla (B), type 2 bulla (C), and type 3 bulla (D).Note the accumulation of air between the layers of the visceral pleura in the pulmonary bleb andthe different connections to the underlying pulmonary parenchyma in B, C, and D.Lipscomb VL et al. Spontaneous Pneumothorax Caused by Pulmonary Blebs and Bullae in 12 Dogs. JAAHA 2003;39:435-445.

Treatment RecommendationsThoracocentesis:Mild pneumothorax, no continued leakage of airTube thoracostomy:>2 thoracocenteses within 24 hrs, thoracocentesis failsto resolve pneumothorax, or tension pneumothoraxThoracotomy:Failed tube thoracostomy, >2 recurrences, bullae notedFailed: pneumothorax persists > 48hrs and persistent clinical signsMedian sternotomy unless able to localizeLobectomy (focal) vs. pleurodesis (diffuse)

Alpha-1 Antitrypsin Major plasma serine protease inhibitorcbms.mq.edu.au Lack of exposes lung tissue to uncontrolled proteolyticattack from neutrophil elastase, culminating in alveolardestruction A1AT deficiency is one of the most common autosomalcodominant inherited disorder in Caucasians In people, specific genotypes are associated with serumlevels which are correlated with severity of emphysema Smoking and A1AT deficiency increase risk andprogression of emphysemaFregonese L et al. Alpha-1 antitrypsin Null mutations and severity of emphysema. Resp Med 2008:102;876-884.

ObjectivesObjective one Perform immunohistochemistry on lung samples fromdogs diagnosed with spontaneous pneumothoraxHypothesisQwickstep.com Lung tissue from dogs diagnosed with spontaneouspneumothorax would have abnormal stainingpattern for folliculin and/or alpha-1 antitrypsin

ObjectivesObjective two Perform DNA sequencing from dogs diagnosed withspontaneous pneumothoraxHypothesishttp://www.free-extras.com/images/siberian_husky_puppy-12926.htm Dogs diagnosed with spontaneous pneumothoraxwould have mutations in the folliculin and/or alpha-1 antitrypsin gene that were associated with thetrait

Materials and Methods Two portions of the studygraham.ces.ncsu.edu Retrospective evaluation for pathology cases of bullousemphysema (n=10) Prospective clinical spontaneous pneumothorax cases(n=5) Research hounds controls (n=6) Selection Criteria No history of trauma No obvious neoplasia or other identified cause ofpneumothorax

Histopathology H&E Trichrome Alpha-1 antitrypsin Folliculinaffected a1at HE - emphysema-early bullaaffected a1at -subpleural trichrome

Candidate Gene Analyses Folliculin Alpha one antitrypsinAGACACACTGTCCCACTCATCCTGCACTGCCATGGAAAGTTTCACAACTGGGTGTTTGAGAATATTTTTGGATGTTTTTGTGGGAAATAGCTCAGGCCGGTGTTGCAACCTTACCTTTAAAGAAAATGTAATTCACCAGAGCGAAAACTGTGTCTTCGTCAAGATCTTTGACCAAATCCACAATTTTTCCTTGGGTTCCCTTCTCTACATAATTGTTGATCTGTTTCTTGGCCTCTTCAGTGTGCCTGAAGTTGATGGTGAAGGCTTCTGAGTGGTACAGKTTCCGACATCCTCTAAAAACTTATTCAGTAGTTTTATGGTGTCGTTGATGAACAGACCGCTGCCGGTGGTCAGCTGCAGCTGGTTGTCTGGCTGGTTGAGGATGCTGAGGAGTTGATGGAAGCCTTGGTGGACTTCCCTCTCTGCTCTCTCAGTGAGGTTGAAACCGAGGCCTTGCATGATCTGGGTGTGGGTGTCCCCCTTGGTGCCCAGAGAGAGCATCGCAAAGGCTGTAGCGATGCTCACGGGGGAGAAGAAGATGTTGGTGGTATTGGACTCTTGGGCCACCTGGCGGTACAAGCTGAAGGCAAAGTCAGCCAexon 5, rs24483703A 4-bp deletion in exon 4 of the FLCN gene. A, Exon4 sequence. The deletion is underlined. B, Unaffected control sequence.C, Affected sequence, showing the wild-type and c.733delTCGG alleles.

ResultsBreeds Husky 4 Golden Retriever 3 Labrador Retriever 2 Collie English Springer Spaniel German Shepherd Gordon Setter Great Dane Lhasa ApsoSex8 females, spayed7 males, neuteredAge 6.7 years, range 3 to 9.7WeightOcpets.ocregister.com 33.2 kgs, range 11.4 to 47.9

Recurrence, 4/15= 27% 5.8 yo, M/N, Mixed Breed, 6 months later 9 yo, F/S, German Shepherd, 38 months later 7 yo, F/S Labrador, 2 weeks later 7 yo, M/N, Siberian husky, 10.5 months laterhttp://www.google.com/imgres?imgurl=http://www.pluspets.net/wpcontent/uploads/2010/05/siberian-huskey1.jpg&imgrefurl=http://www.pluspets.net/siberian-husky-true-winterdog/&h=495&w=612&sz=63&tbnid=Mt_ICMC2_ovF6M:&tbnh=110&tbnw=136&prev=/images%3Fq%3Dsiberian%2Bhusky&zoom=1&q=siberian+husky&usg=__cpHxuaggtjYLcuaMQmKlczf0C68=&sa=X&ei=QbOgTIrgAsPwnge1tLifDQ&ved=0CDIQ9QEwAw

Histopathology (7/15 multifocal bulla) Emphysema: focal, diffuse, multifocal Fibrosis: subpleural > interstitium, milddiffuse/multifocal, moderate diffuse/multifocal,minimally different from controls Folliculin: only slight increase in staining intensity inbronchiole epithelium, slight decrease in pleura, nodifference in cell distributionjmg.bmj.com

Alpha 1 Antitrypsin IHCa1at sub-pleural peribronchial perivascular intralveolarp value 0.0000002943 0.8185399304 0.1166711774 0.3473323796affected a1at - subpleuralcontrol a1at - subpleural

Genotyping Resultsgene status no. animals/genotype Chi-squarevalue, probAllelefrequency1,1 1,2 2,2 1 2Chi-squarevalue, probA1AT N 6 0 0 3.75, 0.153 12 0 1.13, 0.288A 2 2 0 6 2FLCN N 6 0 012 0monomorphicA 4 0 0 8 0monomorphicCases: 2 Labradors, 1 Golden retriever, 1 Alaskan husky

Conclusions Focal to multifocal or diffuse emphysema No difference in folliculin staining Decreased subpleural staining for alpha-1antitrypsin In the mutations studied, no association with the trait

Future Work Gene expression analyses qRT-PCR lung samples, folliculin and alpha-1 antitrypsin Serum levels of A1AT Correlate with degree of emphysema CT lung densitometry Evaluate treatment options for SPOcpets.ocregister.comerj.ersjournals.com

Recommendations for SP Surgery vs. medical management Higher success rates Lower recurrence rates Lower mortality rates Shorter hospitalization timesOcpets.ocregister.com Median sternotomy: multifocal bullae common Thoracoscopy Pleurodesis for diffuse disease? STOP Smoking!!!! Stress management

ReferencesAu JJ et al. Use of CT for evaluation of lung lesions associated with SP in dogs: 12 cases(1999-2002). JAVMA 2006;228(5):733-7.Fregonese L et al. Alpha-1 antitrypsin Null mutations and severity of emphysema. Resp Med2008;102:876-884. Holtsinger RH et al. Spontaneous Pneumothorax in the Dog: A Retrospective Analysis of 21cases. JAAHA 1993;29:195-208.Lee SH et al. Association between anger and first-onset primary spontaneous pneumothorax.General Hospital Psychiatry 2008;30(4):331-336. Lipscomb VL et al. Spontaneous Pneumothorax Caused by Pulmonary Blebs and Bullae in 12Dogs. JAAHA 2003;39:435-445. Peuerto DA et al. Surgical and nonsurgical mgmt of and selected risk factors for SP in dogs: 64cases (1986-1999). JAVMA 2002;220(11):670-4. Valentine A et al. Spontaneous Pneumothorax in Dog. Compendium 1996;18(1):53-63.