Pulmonary ABIM Cerficaon Exam Review Course

Leslie Zimmerman, MD Professor of Clinical Medicine, UCSF ICU Director, SFVAMC

Conflict of Interest/Disclosures n None

1 Relave Value? n Medical Content • CV 14% • Pulmonary 10% • ID 9% • GI 9% n Cross Content • Critical Care 10% • Geriatrics 10% • Prevention 6% • Women’s Health 6%

Relave Value? n Pulmonary: • Obstructive disease: 20% • Pulmonary vascular disease: 12% • Pneumonia: 10% • Pleural Disease: 10% • Restrictive & Interstitial: 10% • 0-2 questions on: ARDS, Sleep, lung cancer, bronchiectasis…

2 Lecture Outline

n Sleep n COPD/Asthma n ILDs n PVD n Solitary Pulmonary Nodule n Etc.

Queson 1 A 65 year-old man with daytime sleepiness is evaluated for sleep apnea. His Epworth sleepiness scale is 11/24.

The polysomnogram reveals an overall apnea-hyponea index (AHI) of 24 (12 events/hour when on his side and 55 events/hour when supine). Lowest oxygen saturation was 86%. He had occasional leg jerks with sleep stage transition; he has no leg symptoms during day.

3 Queson 1 65 yom with overall AHI of 24 (12 on side & 55 when supine). Nadir O2 sat’n = 86%. Occasional leg jerks with sleep stage transition; no leg symptoms during day. He should be offered: A. Screening for iron deficiency B. Modafinil C. Nighttime oxygen D. APAP E. BPAP-ST

Sleep Disorders: Office Visits

www.nhlbi.nih.gov/about/factbook-05/chapter4.htm

4 Classic paent with OSA

Obesity = #1 risk factor

Genetics Upper airway/facial abnormalities (nasal congestion)

Tonsils! en.wikipedia.org Post-menopause Hypothyroidism/ Acromegaly Deeper stages of sleep, neural input to upper airway declines, decreased airway tone, tongue falls back.

Not Obese?

http://tonsillectomyrecovery.com/swollen-tonsils/

http://www.sublimis.com

5 OSA Disruption in sleep causes daytime sleepiness

Epworth Scale can estimate “sleepiness” 10 = Sleepy 18 = Very sleepy

http//:epworthsleepinessscale.com

(Respiratory Disturbance OSA Index) RDI = AHI + milder hyponeas that don’t meet criteria but disrupt sleep 10 seconds 10 seconds

Air flow

“Hyponea” requires 4% desaturation

Apneas + Hyponeas/hour = AHI

6 OSA and Death

Untreated severe OSA (AHI > 30/hour) 3-6 fold increased risk of all-cause mortality compared to individuals without OSA.

IN CONTRAST: Patients with untreated mild OSA may not be at increased risk for mortality compared to individuals without OSA.

Marin JM et al. Lancet 2005;365(9464):1046.

If AHI of 5-15 and OSA • Asymptomatic Severity • Low Epworth • No HTN/CAD/CVA Mild: AHI 5-15 • Not “mission critical” Moderate: AHI 15-30 Many would not treat Severe: > 30 TREAT Medicare reimbursement AHI > 5 if symptoms (sleepiness, fatigue), signs of disturbed sleep (snoring, restless sleep, respiratory pauses), or HTN/CAD/CVA, or job requires Rx AHI > 15 in everyone

7 Mandibular Advance Device If AHI < 15, sleepy & can’t tolerate mask à MAD

We use them for symptomatic patients with mild disease who can’t tolerate PAP Repeat sleep study Q. Severe OSA? (AHI > 30) with device to check Wrong answer is MAD for efficacy

Our paent AHI of 24 = moderate sleep apnea Nadir O2 sat’n = 86%. Occasional leg jerks with sleep stage transition; no leg symptoms during day. He should be offered: A. Screening for iron deficiency He just has myoclonic B. Modafinil jerks with C. Nighttime oxygen falling asleep, D. APAP no RLS or E. BPAP-ST PLMD Treatment for narcolepsy

8 Our paent AHI of 24 = moderate sleep apnea Nadir O2 sat’n = 86%. He should be offered: C. Nighttime oxygen Improves desaturation but D. APAP not AHI, not daytime E. BPAP-ST sleepiness, & not BP in HTN patients* * N Engl J Med 2014; 370:2276-2285 WON’T ASK: CPAP vs. APAP vs. BPAP for the average person with OSA à No study shown superiority

Posive Airway Pressure Machines • Simplest CPAP • Set pressure to bring AHI < 5/hr • Set mid point @ level to bring AHI < 5/ hr +/- 3 or 4 above and below APAP • Can check average pressure needed at next visit (can be used to do “titration”)

• Set EPAP to bring Apneas < 5/hr; IPAP until AHI/RDI < 5/hr • USE: BPAP • Comfort if required pressure high • Supports Tidal Volume à essentially “pressure support ventilation”

9 BPAP

BPAP-S* (Regular) BPAP-ST** • OSA needing • Central Sleep Apnea high pressures • Obesity Hypoventilation (comfort) • NM disease • Chronic respiratory failure

*S= Spontaneous **ST = Spontaneous • No effort, no breath + Timed delivery if no effort

Basically a Non-invasive Ventilator

Our paent AHI of 24 = moderate sleep apnea Nadir O2 sat’n = 86%. He should be offered: D. APAP Given his big difference between E. BPAP-ST side and supine, compliance may be better with APAP (but CPAP would be correct answer as well)

No report of: • Obesity Hypoventilation • Central Sleep Apnea • NM disease • Chronic respiratory failure

10 What were those OSA numbers?

n AHI 5-15 & symptoms or HTN/CAD/CVA à PAP (MAD if can’t comply with f/u sleep study to prove efficacy). If “mission critical” job à PAP because only way to monitor compliance! n AHI 15-30à PAP n AHI > 30 and esp. if < 70 years old, clearly at increased CV mortality if not treated (so we really encourage use!)

Queson 2 A 59 year old man comes to the ED with a COPD exacerbation triggered by nearby forest fires. There is no increase in cough or purulence. He is on home tiotropium, formoterol, ICS and as needed albuterol. He is wheezy but responds to albuterol/ipatropium neb and you anticipate that he will be able to go home. O2 saturation is 91%. You add: A. Home O2 by NC at 2 LPM B. Azithromycin 250 mg daily C. Roflumilast daily D. Theophylline daily E. Prednisone 40 mg x 5 days F. Doxycycline x 7 days

11 2004: Worldwide Leading Causes of Death

Affects 9% of World Population By 2020, will move to 3rd leading cause of

Millions death

http://www.who.int/mediacentre/factsheets/fs310_2008.pdf

In US, only common disease with RISING mortality

Percent Change in Age-Adjusted Death In US, h Rates, US, 1965-1998 (proportion of 1965) in COPD deaths is driven by 3.0 CAD CVA Other COPD All very large CVD Other h in 2.5 women. In 2000, 2.0 for 1st time, more 1.5 women

1.0 died of COPD 0.5 than men - 59% - 64% - 35% +163% - 7% in US. 0

http://www.goldcopd.org

12 COPD Pathogenesis: Aging + Genes + Noxious Smuli

Lung Aging

Healthy

COPD

Lung Mature Total dysfunction Lungfunctionalveoli) (FEV1; 18-25 years 130-140 years Chest 2009;135:173. In US, 15-20% of COPD caused in part by occupational exposures (esp. dusts)

In non-smokers, environmental exposure is primary risk factor

World Health Organization

http://www.who.int/heli/risks/indoorair/en/webiapmap.jpg

Indoor smoke from biomass solid fuels à Contribute up to 35% of COPD in above countries

13 Diagnosis: PFTs n Low FEV1/FVC = diagnosis of obstructive disease (Asthma, chronic bronchitis, emphysema) n FEV1 = severity of obstruction n TLC ↑TLC supports obstructive ↓TLC diagnoses restrictive disease disease

Especially emphysema Also long-standing poorly controlled asthma

n DLCO: low in “airsac” disease and PVD, not asthma

CT: Map of the lungs?

Can diagnose emphysema (not asthma or chronic bronchitis). Not (yet) able to predict FEV1, but More emphysema on CT à higher mortality

Ann Intern Med 2014;161:863

14 Queson 2 A 59 year old man comes to the ED with a COPD exacerbation triggered by nearby forest fires. There is no increase in cough or purulence. He is on home tiotropium, formoterol, ICS and as needed albuterol. He is wheezy but responds to albuterol/ipatropium neb and you anticipate that he will be able to go home. O2 saturation is 91%. You add: A. Home O2 by NC at 2 LPM < 88% or PaO2 < 55 or < 59 if ↑ Hct or RHF B. Azithromycin 250 mg daily C. Roflumilast daily D. Theophylline daily E. Prednisone 40 mg x 5 days F. Doxycycline x 7 days

Queson 2 A 59 yom with a COPD exacerbation triggered by nearby forest fires. No increase in cough or purulence. On home tiotropium, formoterol, ICS prn albuterol. Wheezy but responds to albuterol and you anticipate that he will be able to go home. O2 saturation is 91%. You add: E. Prednisone 40 mg x 5 days

JAMA. 2013;309:2223-2231.

40 mg x 5 days 40 mg x 14 days

Just as good for average COPDer

15 COPD: Acute Exacerbaon Rx Not much new n Short-acting albuterol = mainstay n Alternative or add short-acting ipratropium n Prednisone n Antibiotics: • Early rx à better outcome in hospitalized patients JAMA. 2010;303(20):2035 • Decrease risk of next exacerbation Eur Respir J. 2009;33(2):282 • MILD exacerbation (no hospitalization needed & only 0-1 of increased dyspnea, sputum purulence, or sputum production): Recommendation àno antibiotic

COPD: Maintenance Rx Tiotropium: n Improves function & decreases exacerbations (UPLIFT trial: Lancet 2009; 374:1171.) n UPLIFT trial: No increase in CV events n TIOSPIR trial: mist vs dry powder no diff in CV events, but they excluded active CAD (recent MI, Vtach, and CHF patients) (NEJM 2013;369:1491) (vs. smaller BMJ. 2011;342:d3215.) n Overall CV risk seems small n Increase in urinary retention in some

16 COPD: Maintenance Rx LABA + Inhaled corticosteroids: improved lung function & decreased exacerbations

(TORCH trial NEJM 2007;356:775). Inhaled corticosteroids: decrease exacerbations but may increase risk of CAP Arch Intern Med. 2009;169:219 Compare to asthma, in which ICS are mainstay. Statins, Vit D: Duds Sildenifil for P HTN and COPD: BAD! Worse oxygenation (AJRCCM. 2010;181: 270.) Our order: prn Albuterol or Combivent, add LAMA (change Combivent to albuterol), add LABA, if asthma component or still having exacerbations add combo LABA/ICS

Queson 2 A 59 yom with a COPD exacerbation triggered by nearby forest fires. No increase in cough or purulence. On home tiotropium, formoterol, ICS prn albuterol. Wheezy but responds to albuterol and you anticipate that he will be able to go home. O2 saturation is 91%. You add: B. Azithromycin 250 mg daily Beyond “triple C. Roflumilast daily therapy”…Can other D. Theophylline daily chronic therapies reduce recurrent E. Prednisone 40 mg x 5 days exacerbations?

You need help with recovery for this exacerbation

17 COPD Exacerbaons Recurrent exacerbations are bad

More exacerbations LungFunction à Faster decline in FEV1

Lung function over lifetime with COPD

Can Azithromycin Help? Albert RK et al. “Azithromycin for Prevention of Exacerbations of COPD” NEJM 2011; 365:689. nAzithromycin (250 mg daily) vs. placebo x 1 year.

Fewer exacerbations Macrolides have (modest) immunomodulatory, anti-inflammatory, and anti-bacterial effects

Exacerbations Exacerbations 5% hearing loss Proportion free of Proportion (NNH =20) days

18 Azithromycin Saga…. Wayne RA, et al. NEJM 2012; 366:1881 nPrescriptions for azithromycin in Tennessee Medicaid registry & sudden death within 10 days – slight increase in sudden death (compared to amoxicillin prescriptions) Vs. Svanström H, et al. NEJM 2013; 368:1704-1712. n Mostly young/middle aged adults à no increased risk.

Original article: Albert RK et al. NEJM 2011; 365:689. nExcluded if Long QTc, other meds that can prolong QT or associated with torsades.

Azithromycin Saga…. RESERVE for: “Carefully selected patients, such as those who continue to have frequent exacerbations in spite of optimal therapy for their COPD with bronchodilators and anti-inflammatory agents.”

After: LAMA, LABA, ICS Check baseline ECG and repeat ECG after starting!

19 Roflumilast

Phosphodiesterase-4 (PDE-4) inhibition n Smooth muscle relaxation n Anti-inflammatory? n Targeted to those with > 2 hospitalized exacerbations/year n No head to head comparison with Azithromycin n Diarrhea/ wt loss problems

Theophylline?

LOW (half) DOSE @ 100 -200 mg twice/day for levels 6-8 mcg/mL (half traditional target) nBenefit as anti-inflammatory medication (not as smooth muscle relaxer – that you likely need full dose)

20 Queson 2 A 59 yom with a COPD exacerbation triggered by nearby forest fires. No increase in cough or purulence. On home tiotropium, formoterol, ICS prn albuterol. Wheezy but responds to albuterol and you anticipate that he will be able to go home. O2 saturation is 91%. You add: B. Azithromycin 250 mg daily C. Roflumilast daily D. Theophylline daily Save for severe COPD - Check for asthma component (trigger control) - Still smoking?

Queson 3

All of the following are risk factors for COPD exacerbations EXCEPT? A. Prior exacerbations B. Lower FEV1 C. Male sex D. History of asthma

21 COPD: Lots of variability in course Exacerbations are bad – more inflammation, more airway remodeling à more rapid decline in FEV1 But who gets exacerbations? v Prior exacerbations v Lower FEV1 (worse you are, the worse you are…) v Women v History of asthma Phenotypes of frequent and infrequent “exacebators”

NEJM 2010;363:1128.

COPD & Asthma

COPD ASTHMA • Older, esp. smokers • Any age, esp. children • Slowly progressive • Episodic • Neutrophils • Eosinophils • Partially reversible • May be fully reversible • Airway remodeling & • Airway remodeling Lung destruction

10% overlap

Manage similar to asthma (ck for allergic triggers, ICS mainstay)

22 Queson 4 A 45 year-old ex-smoker with 5 years of progressive DOE has the following CXR

And CT scan of Lung Bases

23 Queson 4 Testing reveals that he has very low levels of alpha-1-antitrypsin (PiZZ variant). Treatment with replacement therapy has been shown to:

A. Decrease risk of lung cancer B. Decrease number of exacerbations/year C. Improve oxygenation D. Prevent liver disease E. Slow decline of FEV1

Alpha 1 An-trypsin Deficiency Panacinar Neutrophil Elastase A1AT n Normal: PiMM n Heterozygotes make enough to be protective n Homozygous PiZZ, PiZnull, PiNullNull elastase unchecked àearly emphysema in smokers, though RARE that lifetime non- smokers get emphysema

24 Liver Disease? n A1AT made in the liver à ZZ variant, it is made but can’t get out of the ER of the hepatocyte à liver damage à cirrhosis n PiNullNull – makes NO A1AT – they do not get the liver disease n IV Augmentation doesn’t help liver

Augmentaon with A1AT n Cost: $60,000 to $150,000/ year n Approved by the FDA if level below the protective level (PiZZ, PiZnull) & COPD n Not in heterozygotes n Not if still smoking n Not if asymptomatic n NIH registry: augmentation decreases rate of decline of lung function & mortality (NOT A RANDOMIZED TRIAL)

25 Queson 4 Testing reveals that he has very low levels of alpha-1-antitrypsin (PiZZ variant). Treatment with replacement therapy has been shown to: Increased risk in A1AT deficiency, but A. Decrease risk of lung cancer no decrease with Rx B. Decrease number of exacerbations/year

C. Improve oxygenation Adding normal D. Prevent liver disease A1AT won’t hurt; but won’t help E. Slow decline of FEV1

Queson 4 Testing reveals that he has very low levels of alpha-1-antitrypsin (PiZZ variant). Treatment with replacement therapy has been shown to:

“ ” Air sac disease, not airway disease B. Decrease number of exacerbations/year C. Improve oxygenation No therapy will improve function, hope to just limit continued damage E. Slow decline of FEV1

26 Queson 5

A 34-year-old woman has Normal periodic shortness of breath despite albuterol, formoterol, high dose inhaled steroids. Spirometry during an episode is Exhalation shown. O2 sat’n during episode is 96%.

The next best step is: Flow A. Check ABPA serology B. ENT evaluation

C. HRCT Inhalation D. Start Montelukast Volume E. Start Pantoprazole

Flow-volume Loops

Normal Exhalation Exhalation Flow Flow Flow Flow Normal Obstruction Inhalation Inhalation Volume Volume

Normal Normal

Restriction Severe Flow Flow Flow Flow Obstruction

Volume Volume

27 Flow-volume Loops Upper Airway Obstrucon Exhalation Exhalation Exhalation Exhalation Exhalation Exhalation Flow Flow Flow Flow Flow Flow Inhalation Inhalation Inhalation Inhalation Inhalation Inhalation Volume Volume Volume

Fixed Variable Variable Large Airway Extrathoracic Intrathoracic

+ -

+ -

Flow-volume Loops Variable Extrathoracic Obstrucon from Vocal Cord Dysfuncon • Psychogenic • Most commonly in women, ages 20 - 40 Normal • May present with respiratory distress

Exhalation Exhalation and dramatic inspiratory stridor

Flow Flow • Loudest noise at throat • Normal ABGs and A-a gradient Inhalation Inhalation Volume • Resolves when asleep • Minimal response to aggressive asthma treatment • Really hard when co-exists with asthma • Diagnosis by endoscopy

28 FV loop Queson 5

The next best step is: A. Check ABPA serology B. ENT evaluation C. HRCT D. Start Montelukast E. Start Pantoprazole Vs. Difficult to control asthma: • Consider: Tiotropium, • Compliance Leukotriene blocker • Allergy trigger review • ABPA serology (steroids & • Smoking cessation itra or voriconazole) • Weight loss if obese • IgE levels (Anti-IgE rx?) • Treat allergic rhinitis • Future: Anti IL5, IL13, IL17 • Check for GERD (PPI)

Queson 6 A 23 year-old woman has increasingly use of prn albuterol for her asthma. Spirometry supports diagnosis. She has asthma symptoms approximately 3x a week and is awakened at night about 3x a month. Afebrile, BP 120/75, RR 16/min. Lungs: no wheezes.

Her peak flow is 400 liters per minute (her best value is 450 LPM).

29 Queson 6 Which of the following asthma medications would be the most appropriate addition to the treatment regimen at this time?

A. Oral proton pump inhibitor B. Oral theophylline C. Low-dose inhaled corticosteroid D. Long-acting beta 2-agonist E. Leukotriene modifier

Management of Asthma Inial Assessment

STEPS 5 & 6

STEP 4 Severe Persistent STEP 3 Moderate Persistent STEP 2 Mild Persistent STEP 1 Mild Intermittent

30 Management of Asthma A Step-Wise Approach

Symptoms Nocturnal STEP 4, 5, 6 Continual symptoms Frequent Severe persistent Limited physical activity Frequent exacerbations STEP 3 Daily symptoms > one/wk Moderate persistent Daily use of inhaler Exacerbations affect activity Exacerbations ≥ 2 times/wk STEP 2 Symptoms >2 times/wk,<1/day >2/mo Mild persistent Exacerbations may affect activity STEP 1 Symptoms ≤ 2 times/wk ≤2/mo Mild intermittent Asymptomatic between exacerbations Exacerbations brief

Management of Asthma Inial Assessment Quick-relief Long-term

High-dose Consider STEP Inhaled steroids Anti -IgE 5 & 6

Med-dose STEP 4 inhaled steroids Severe Persist.

Low-med dose* Long-acting STEP 3 inhaled steroids beta-2 agonist Moderate Persistent

Low-dose* STEP 2 inhaled steroids Mild Persistent

Short-acting prn STEP 1 beta-2 agonist Mild Intermittent Patient education & environmental control at each step

* Alternatives: leukotriene modifiers, cromolyn, nedocromil, theophylline

31 Management of Asthma Inial Assessment Quick-relief Long-term

High-dose Consider STEP Inhaled steroids Anti -IgE 5 & 6

Med-dose STEP 4 inhaled steroids Severe Persist.

STEP 3 Low-med dose* Long-acting TiotropiumModerate Persistent inhaled steroids beta-2 agonist

Low-dose* STEP 2 inhaled steroids Mild Persistent

Short-acting prn STEP 1 beta-2 agonist Mild Intermittent Patient education & environmental control at each step

* Alternatives: leukotriene modifiers, cromolyn, nedocromil, theophylline

Asthma- Tiotropium in moderate to severe asthma NEJM 2012;367:1198 In asthma patients poorly controlled with standard therapy. Tiotropium vs. placebo • Improved lung function • Decreased time to exacerbation • Decreased # of severe exacerbations • No increase in adverse events

Not a sub, but an “add-on”

32 Take home points

n If patient moves from intermittent à mild persistent, add controller medication (best for most = inhaled corticosteroid) n If poor control on ICS: increase ICS or add long acting b-agonist (deals with concerns about safety of LABA) n Long acting b-agonist without a controller medication is always the wrong answer n For emergency rescue, short acting b-agonist always the right answer

LABA- Safety? n Lots of large studies with mixed results of the potential for increased mortality with LABA in a small number of patients n Related to LABA or non-compliance with ICS? Studies are so far insufficient to tell

THIS IS NOT AN ISSUE WITH COPD

33 Queson 6 Which of the following asthma medications would be the most appropriate addition to regimen at this time (only on short acting b-agonists)? Not in asymptomatic A. Oral proton pump inhibitor pts B. Oral theophylline C. Low-dose inhaled corticosteroid D. Long-acting beta 2-agonist E. Leukotriene modifier

All acceptable by guidelines, in practiceà like ICS; Caveat: some young people w/ exercise induced asthma do well on LT agents. Smokers have blunted response to ICS.

Queson 7 A 32 year old patient has poorly controlled asthma despite inhaled steroids, LABA, LTR-Blocker. Which of the following would predict a good response to Anti-IgE therapy? A. Eosinophilia B. Extremely high IgE levels (>2000 IU) C. Latex allergy D. Sensitization to dust mites

34 An-IgE (Omalizumab)

n Consider for Steps 5 & 6 (difficult to control asthma) n Binds IgE à complex cleared n Rx: fewer exacerbations & less steroid needed; no change in baseline FEV1

An-IgE (Omalizumab) n Need to get IgE to extremely low levels for it to work (very low levels trigger mast cell degranulation) n Baseline serum IgE should be High, but not between 30 - 700 IU/mL TOO HIGH n + Skin test or RAST to a perennial aeroallergen (e.g., dust mite, animal danders, cockroach, molds) n Sq each 2-4 weeks n Anaphylaxis 1:1,000 n Minimum dose $12,000/year

35 Queson 7 A 32 year old patient has poorly controlled asthma despite inhaled steroids, LABA, LTR-Blocker. Which of the following would predict a good response to Anti-IgE therapy? A. Eosinophilia Though usually a partner B. Extremely high IgE levels (>2000 IU) TOO high C. Latex allergy Best with aeroallergen D. Sensitization to dust mites

Queson 8 30 year-old woman was exposed to chlorine gas 2 months ago at work & now has a persistent cough & mild SOB. At exposure, she noted irritation of her eyes and mucus membranes. Immediately after the exposure, she developed a cough. A chest x-ray was normal. No treatment was given. The patient has no history of asthma, but since this, has been wheezing at night.

Exam is unremarkable with clear lungs. Spirometry: FVC of 89% of predicted

FEV1 of 84% of predicted FEV1/FVC 73% Methacholine challenge + for bronchial hyperresponsiveness

36 Queson 8 Which of the following is the most likely diagnosis?

A. Cryptogenic organizing pneumonitis (COP) B. Hypersensitivity pneumonitis C. Diffuse panbronchiolitis D. Reactive airways dysfunction syndrome

Occupaonal Asthma 20-30% of new onset adult asthma = occupational!

Occupational Acquired sensitization asthma in the workplace Irritant-induced asthma Multiple exposures to irritant Reactive airways Single big exposure to dysfunction irritant

Non-immunologic

37 Reacve Airways Dysfuncon Diagnosc Criteria n Exposure to irritant in high concentration n Onset of symptoms after single exposure within 24 hrs; persist for at least 3 months and sometimes years! n Symptoms of asthma n PFTs +/- airflow obstruction, but Methacholine test positive

Brooks SM et al. Chest 1985;88:376

RADS Take home points n “Big Bang” à big exposure, symptoms right away n + methacholine challenge n Rx like asthma, though typically harder to control n CHLORINE! (Including mixing household cleaners) n Gulf War à sulfur mustard gas

38 Queson 8 Typically slower onset; HRCT scan + Which of the following is the most likely diagnosis?

A. COP B. Hypersensitivity pneumonitis C. Diffuse panbronchiolitis D. Reactive airways dysfunction syndrome

Japanese (Specific HLA), chronic sinusitis, productive cough, diffuse lung nodules à Rx Erythromycin x 6-24 months

Crytogenic Organizing Pneumonis n Former Bronchiolitis Obliternans Organizing Pneumonitis “BOOP” n Like the flu that keeps coming back n Fevers, infiltrates that come and go n Biopsy n Treat with steroids

39 Queson 9 77 year old man has progressive dyspnea x 2 years. No sputum, hemoptysis, weight loss, or sweats. He previously smoked 1 ppd for 40 years, quit 15 years ago. PMH: HTN and peptic ulcer disease. Meds: lisinopril and omeprazole Exam: afebrile, RR 16, SaO2 92% RA Crackles bilaterally at bases + Clubbing Labs: negative serology for rheumatologic dz

Chest X-ray

40 HRCT

PFTS FVC 67% predicted FEV1 72% predicted TLC 74% predicted DLCO 55% predicted

Oxygen saturation is 92% at rest and 87% after ambulation

41 Queson 9 77 yom former smoker with progressive dyspnea and restriction on PFTs. In addition to oxygen, which of the following is most appropriate at this time? A. VATS lung biopsy B. Listing for single lung transplant C. Prednisone D. Pirfenidone E. Sildenafil

IPF – What DOESN’T work “Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis” NEJM 2012;366:1968. n Stopped early because of INCREASED death in steroid patients! PREDNISONE SHOULD NOT BE USED FOR IPF

“Randomized Trial of Acetylcysteine in Idiopathic Pulmonary Fibrosis” NEJM 2014; 370:2093 nNo benefit

42 Nintedanib and Pirfenidone Won’t ask you to choose Nintedanib Pirfenidone NEJM 2014; 370:2071 NEJM 2014; 370:2083 $$$ $$$ Receptor blocker of Antifibrotic agent that multiple tyrosine kinases inhibits TGF-b-stimulated collagen synthesis Follow LFTs Follow LFTs Rumbly gut Rumbly gut MDC Conference MDC Conference Slows decline Slows decline

Queson 9 77 yom former smoker with progressive dyspnea and restriction on PFTs. In addition to oxygen, which of the following is most appropriate at this time? A. VATS lung biopsy Biopsy for confusing cases, not classic IPF B. Listing for SLT by CT, symptoms, C. Prednisone demographics. IPF D. Pirfenidone flare can be triggered by lung & non lung E. Sildenafil surgery Definite NO

43 HRCT: Classic for IPF Bilateral, lower lobe predominant

Traction Subpleural bronchiectasis honeycombing

Consider other dx: - Age < 55 - Productive cough - Extensive GGOs

IPF

End stage Honeycombing No drug will ever fix this part

44 Queson 9 77 yom former smoker with progressive dyspnea and restriction on PFTs. In addition to oxygen, which of the following is most appropriate at this time? B. Listing for SLT Age doesn’t rule out D. Pirfenidone (but old), but DLT better outcomes, & E. Sildenafil track decline to see if might benefit Echo if DLCO < 35% to check for pulmonary HTN

IPF – Exacerbaon IPF exacerbation: 75% mortality n Think about CHF n Think about PE n HRCT to look for classic GGO n BAL (if you can) to look for infection n Antibiotics unless confident no infection n Prednisone 1 mg/kg per day orally or methylprednisolone 1 to 2 g per day intravenously

45 IPF-Summary Some bad options à Steroids only for exacerbations, otherwise NO STEROIDS Symptomatic but not end stage, consider referral for Nintedanib or Pirfenidone N or P WILL NOT IMPROVE, only slows decline (not useful for severely debilitated) No data to chose between the 2 Sildenafil if Pulmonary HTN Exacerbation? Call for help

Queson 10 34 year old man has DOE x 6 months and cough productive of yellow sputum. No fever, chills, or hemoptysis. HIV negative. Exam is normal. Sputum smears are negative for AFB. He has had a pet pigeon for the past 2 years. Pulmonary function tests: FEV1/FVC 83% predicted ABG 7.49/30/60 TLC 68% predicted DLCO 50% predicted

46 Chest X-ray

Chest CT Scan

47 Lung Biopsy

Queson 10 Which of the following is the most likely diagnosis? A. Idiopathic pulmonary fibrosis B. Lymphangioleiomyomatosis C. Mycobacterium Avium Complex (MAC) infection D. Hypersensitivity pneumonitis

48 Intersal Lung Diseases

n Characterized by restriction (low TLC) on PFTs with low diffusion capacity and desaturation with exercise (or if bad à hypoxemia at rest) n High resolution Chest CT scan is almost always the right answer to “what to do next” if hasn’t been ordered • Some ILDs have classic findings • Shows where to biopsy

“Mosiac” Paern on HRCT Inspiration Expiration Vs.

If small airways inflamed, air Could be “perfusion” can’t exit with exhalation. On CT issue: scan, involved lung areas remain - PE black. Mosaic suggests of small - CHF airway (bronchiolar) disease: HP, Or not a perfusion Sarcoidosis, RB-ILD… BUT problem à just patchy SOMETHING WRONG! alveolar infiltrates

49 Ground Glass = acve alveolis

HRCT What to order? Get inspiratory and expiratory views (small airway disease) Plus prone & supine images. Can open up atelectasis that can be confused with an ILD

50 Hypersensivity Pneumonis Chronic granulomatous inflammation after repeated inhalation of environmental antigens n Can present as acute, subacute or chronic dz n No single test is diagnostic: + serology just tells exposure n Suspect when there is a • History of recurrent “pneumonias” • Symptoms develop after moving to a new job or home or birds or water damage/visible mold in work/home • Improvement in symptoms when away from work/home • No eosinophilia

ILD: HP Hypersensitivity pneumonitis: centrilobular nodules, ground glass opacities, and air trapping (mosiac pattern) on expiratory views

51 Lung Biopsy

Granulomas a bit less well formed than sarcoid But will not ask for diagnosis based just on biopsy

How many of these ILDs do you need to know? My Picks are: n Hypersensitivity Pneumonitis • Because non-drug intervention can cure (i.e., removing the antigen) n Sarcoid • Common and distinguishing HRCT n IPF • Common and distinguishing HRCT, new Rx

52 Sarcoid

Sarcoid on HRCT Sarcoid: adenopathy and nodular thickening of bronchovascular bundles (lumpy- bumpy), centrilobular nodules.

53 ILD: Sarcoid Disease @ bronchovascular bundles

MAC infecon

Clear increase in prevalence “Tree-in-bud” in past few decades = infection

54 MAC Infecon Spectrum n HIV n COPD – older men, upper lobe, cavitary n In prior bronchiectasis (CF patients) n Healthy women in 50s: diffuse infiltrates à cause bronchiectasis • This subgroup à some have hypersensitivity reaction to MAC; removal from exposure may

help. Biofilm in Hot Tubs and shower heads. Want hot water > 130oF

Mycobacterium avium Lung If smear + or 3-4 Disease + cultures àmore Diagnostic criteria: likely to progress Symptoms + x-ray (nodules, cavities, or bronchiectasis) with: n Positive cultures from at least 2 separate sputum samples OR n Positive culture from at least 1 bronchial wash OR n Transbronchial or other lung biopsy with characteristic histology and positive culture on either biopsy or sputum Am J Resp Crit Care Med 2007;175:367

55 Treatment of Mycobacterium avium Lung Disease Check for macrolide resistance: at start, and if fails to respond at 6 months, or if relapse post Rx n For nodular/bronchiectasis: macrolide (clari or azithro), ethambutol, & rifamycin (rifampin or rifabutin) 3 times weekly n For cavitary disease : same drugs given daily +/- streptomycin or amikacin n Goal: 12 months of negative sputum cultures while on therapy--total duration is often 14-18 months

Am J Resp Crit Care Med 2007;175:367

Proliferation of atypical pulmonary LAM interstitial smooth muscle with cyst formation

Classic LAM story: 35 year old woman with dyspnea and pneumothorax or chylothorax

56 Queson 10 34 yo man with a bird. Which of the following is the most likely diagnosis? Too young Young women; A. Idiopathic pulmonary fibrosis obstruction not restriction on B. Lymphangioleiomyomatosis PFTs C. Mycobacterium Avium Complex (MAC) infection Should have tree-in D. Hypersensitivity pneumonitis bud on CT scan; productive cough Typical HRCT, bird exposure favor HP Diagnosis important – need to remove antigen (bird)!

Queson 11 33 year-old woman presents with intermittent fever, night sweats, migratory joint pain, and red, painful nodules on her shins. She has no pulmonary symptoms. Chest x-ray:

57 Queson 11 Bronchoscopy with transbronchial biopsy: non- caseating granulomas. Stains and cultures for fungi and mycobacteria were negative.

Queson 11 Which best describes the status of her lung disease in 2 years? A. Progression to advanced obstructive lung disease B. Progression to advanced interstitial lung disease with fibrosis C. Progression to pulmonary hypertension D. Normal lung function

58 Overview of Sarcoidosis n Multisystem granulomatous disorder of unknown etiology characterized by non-caseating granulomas in involved organs n Incidence varies geographically; much more common in African-Americans (lifetime risk of 2.4%) n Usually presents ages 10 - 40, half detected by CXR without symptoms n Any organ can be involved, lungs most frequent (90%)

Should you bx asymptomatic pts with hilar adenopathy? Won’t ask

Sarcoidosis-Staging n Stage I Bilateral hilar adenopathy n Stage II Above + interstitial infiltrates (upper>lower lung zones) n Stage III Interstitial disease with shrinking hilar nodes n Stage IV Advanced fibrosis

Extra-pulmonary disease-skin (E. nodosum, lupus pernio), eyes, liver, lymph nodes most frequent

59 Sarcoidosis: Dx & Rx n Histology = granulomas, must exclude infection! n Usual indications for treatment are: worsening pulmonary symptoms, lung function, progressive radiographic changes, cardiac, eye, neuro, disfiguring skin lesions, high calcium n Therapy is NOT indicated in • Asymptomatic stage I disease patientsLove to ask! • Asymptomatic patients with stage II and mildly abnormal lung function n Follow first for 3-6 months (some say 6-12, even with mild-moderate) and document impairment of Won’t ask lung function

Sarcoidosis

n No drug has been shown to change the course n Steroids treat granulomatous disease which can cause symptoms but won’t change fibrotic disease • EXAMPLE: hypercalcemia very responsive! n Inhaled corticosteroids ? Most experts don’t give n Lupus pernio skin changes= rare to have remission, but seems to be better with infliximab

n If severe lung disease by PFTs or need for Oxygen à get Echo to check for pulm HTN

60 Queson 11

Her lung disease in 2 years? She has Stage I CXR, but lots of symptoms. She had Lofgren's syndrome: “Acute” sarcoid with abrupt onset with erythema nodosum, hilar adenopathy, migratory polyarthralgias, and fever seen primarily in women. • Strongly associated with HLA-DQB1*0201 • Good prognosis and spontaneous remission in 85-95%. Rx only if painful arthritis.

Queson 12 46 year old woman has 4 weeks of fever, night sweats, cough, and 10 lb weight loss. She also has arthralgias, epistaxis, nasal congestion. 2 weeks of clarithromycin did not relieve her symptoms. Now has hemoptysis. Exam: 99.7, RR 24/min, crackles right chest, 1+ edema WBC 6800/mm3 Hgb 10.3 Platelets 568,000/mm3 Creatinine 1.3 mg/dL Urinalysis: 2+ protein, 0 WBCs, rare RBC casts

61 X-ray

American Journal of Roentgenology. 2009;192:676-682

Queson 12 Which of the following is the best diagnostic step? A. Serum angiotensin-converting enzyme B. Rheumatoid factor C. Antineutrophil cytoplasmic antibodies D. Culture of bronchoalveolar lavage fluid E. Percutaneous needle biopsy of the lung

62 Pulmonary-Renal Syndromes

Systemic vasculitis ANCA? Wegener’s granulomatosis C-ANCA 80% P-ANCA 10% Microscopic polyangiitis P-ANCA 70% Pauci-immune GN Most P-ANCA Churg-Strauss (allergic angiitis ½ ANCA and granulomatosis) Goodpastures syndrome P-ANCA 10-40% Systemic lupus erythematosus Some + Henoch-Schonlein purpura Infection Post-streptococcal glomerulonephritis, endocarditis

Any + ANCA= bad news. You may not know which vasculitis it is…., but always abnormal.

Approach to Pulmonary-Renal Syndromes n Serologic tests: ORDER • Anti-GBM Abs, anti-neutrophil cytoplasmic Abs (ANCA), ANA n ANCAs are positive in 90% of those with generalized Wegener’s (PR3-ANCA or “C- ANCA”) n Tissue should be obtained to provide evidence of vasculitis • Skin (easy), Kidney, or lung (surgical biopsy) • If Anti-GBM possible, kidney better to bx than lung

63 Sarcoid is not pulm-renal Queson 12 syndrome Which of the following is the best diagnostic step? A. Serum angiotensin-converting enzyme B. Measure rheumatoid factor Lupus not RA C. Antineutrophil cytoplasmic antibodies D. Culture of bronchoalveolar lavage fluid E. Percutaneous needle biopsy of the lung

Reasonable, but Not enough tissue fungi, TB can not to see vessel explain GN

Queson 13 30 year old man has increasing dyspnea with exercise and chronic daily productive cough since adolescence. He also reports frequent bronchial and sinus infections, treated with multiple courses of antibiotics. Twice he was admitted for pneumonia. He has a 20-pack year history of smoking. No other medical problems or prior surgeries. He works in an office. Exam: SaO2 86%, diffuse crackles, and digital clubbing.

64 Chest X-ray

Chest CT Scan

65 Queson 13 Which of the following should be ordered to establish the most likely diagnosis? A. Serum IgG and IgE for Aspergillus B. Serum IgA and IgG levels C. Sweat chloride measurement D. Nasal brushing for EM analysis

E. Serum α1-antitrypsin level

Bronchiectasis: Causes • Bronchopulmonary infections – Bacterial, fungal, mycobacterial • Bronchial obstruction

– Foreign-body, tumors, lymph nodes • Immunodeficiency states – IgA, IgG deficiency • Hereditary abnormalities – Cystic fibrosis, ciliary dyskinesia, α-1 antitrypsin deficiency • Miscellaneous: Rheumatoid, Sjogren’s

66 Bronchiectasis work-up in adults Blood Imaging Other CBC HRCT Spirometry IgA, IgE, RF Sinus CT Sputum - Aspergillus - MAC

IgG Sweat chloride subclasses Nasal brush for EM Bronchoscopy

Primary Ciliary Dyskinesia n Chronic cough, rhinitis, and sinusitis n Cilia do not beat normally n Triad of situs inversus, chronic sinusitis, and bronchiectasis = Kartagener’s syndrome n Situs inversus is present in 50% of patients with primary ciliary dyskinesia

67 Queson 13 Which of the following should be ordered to establish the most likely diagnosis? A. Serum IgG and IgE for Aspergillus ABPA B. Serum IgA and IgG levels C. Sweat chloride measurement D. Nasal mucosal biopsy

E. Serum α1-antitrypsin level All can cause bronchiectasis with purulent sputum and all part of an adult work-up, but with situs inversus, start with evaluation of cilia

Queson 14

65 year old man with a history of TB has intermittent hemoptysis but no fevers/chills/ weight loss.

Recent spirometry: FEV1 1.0L (40%), FVC 1.5L. Today he coughs up 200 mL of bright red blood. Exam: afebrile, BP 145/82, pulse 104, RR 18, SaO2 93% on air. Bronchoscopy: blood coming from the left upper lobe bronchus.

68 Chest X-ray

Chest CT Scan

69 Queson 14

What is the best management option for this patient at the present time? A. Bronchial arteriography with embolization B. Four first-line drugs for tuberculosis C. Intravenous Amphotericin B D. Left upper lobe resection

Causes and Management of Massive Hemoptysis Massive usually means > 200 mL in 24hrs Most common causes include: 1) TB (active or inactive disease) 2) Bronchiectasis More commonly 3) Lung cancer à chronic mild 4) Mycetoma hemoptysis 5) Immunologic diseases (ANCA- associated vasculitis, Goodpasture’s, SLE)

70 Management of Massive Hemoptysis n First, protect the airway n Bronchoscopy can localize; make some diagnoses n Majority of massive bleeds have bronchial circulation à Bronchial arteriography with embolization next step. 85% successful especially with bronchiectasis and mycetomas. Less so with cancer n Surgery is definitive, but high M&M if done urgently

Our patient has a mycetoma, and actively bleeding→ arteriography and embolization successful

Queson 14

What is the best management option for this patient at the present time? A. Bronchial arteriography with embolization B. Four first-line drugs for tuberculosis C. Intravenous Amphotericin B

D. Left upper lobe resection Old cavity; looks like a classic Doesn’t penetrate fungus ball well; fungal mycetoma Itraconazole may

71 Queson 15

Which of the following are used in the routine treatment of patients with idiopathic pulmonary arterial hypertension? A. Calcium channel blocker B. Digoxin C. Epoprostenol D. Nitric oxide E. Warfarin

Pulmonary Hypertension

Endothelial Cell Endothelin NO Prostacyclin ET-R Smooth Muscle Smooth muscle Cell contraction Smooth muscle relaxation Endothelin is also smooth muscle mitogen

72 Pulmonary Hypertension- RX

Endothelin receptor-blockers Prostanoids: Bosentan (Oral) Prostacyclin =Epoprostenol Ambrisentan (Flolan) continuous IV Iloprost (Inhaled) • Hepatotoxicity Treprostinil (IV or sq)

Phosphodiesterase Smooth muscle Calcium Channel inhibitors: relaxation Blockers Prolong NO action: Only 5-10% Sildenafil & Vardenifil respond

Pulmonary Hypertension- RX

General recommendations: n Treat primary cause if there is one n Oxygen if desaturates n Anticoagulation in chronic PE (mainstay) and in IPAH n Diuretics if needed n Advanced therapy guided by PA catheter Love to ask

73 Queson 15 Only 5% with sustained Which of the following are used in benefit, never do without R the routine treatment of heart cath to prove efficacy patients with IPAH? OK if LV failure A. Calcium channel blocker B. Digoxin C. Epoprostenol If severe D. Nitric oxide E. Warfarin No portable system yet

Endothelial disruption: in-situ clotting, even small clots can tip a patient over Better outcomes: Circ 2014; 129(1): 57-65. BUT ONLY IN IDIOPATHIC PAH.

Queson 16 A 62 year old patient with COPD complains of SOB and has a negative CTA for PE, but the CT scan shows

5 mm

Nodule is not visible on Chest x-ray and there are no prior CT scans. PFTs with FEV1 of 65%.

74 Queson 16

You recommend: A. Bronchoscopy B. PET scan C. Repeat Chest CT in 6 months D. Transthoracic needle aspirate E. Surgical resection

Solitary Pulmonary Nodule FLEISCHNER SOCIETY 2005 Recommendations F/U & Management of Incidental Nodules Detected at Nonscreening CT Nodule Size Low-Risk Patient High-risk Patient (Smoker, radon (mm) asbestos, uranium, 1st degree relative or spiculated nodules)

< or = 4 mm No f/u needed F/u CT 12 mo; if (risk < 1 %) unchanged, no further f/u

>4-6 mm F/u CT 12 mo; F/u CT 6-12 mo then if unchanged, no f/u 18-24 mo if no change

>6-8 mm F/u CT 6-12 mo, then F/u CT 3-6 mos, then 9-12 18-24 mo if no change and 24 mo if no change

>8 mm F/u CT 3, 9, and 24 mo F/u CT 3, 9, and 24 mo if NOT changing if NOT changing vs. PET, FNA, resection vs. PET, FNA, resection

75 Solitary Pulmonary Nodule FLEISCHNER SOCIETY 2005 Recommendations F/U & Management of Incidental Nodules Detected at Nonscreening CT Nodule Size Low-Risk Patient High-risk Patient (mm)

Translation: ü Bigger nodules more worrisome ü F/u CT at “3, 9, 24 months” means from the 1st CT (not 9 months after the 3 month CT) ü > 8 mm, we tend to work up now rather than watch CT scans unless other significant morbidities ü 2 year stability works for most solid nodules ü For “ground glass” nodules, don’t know – we use 3 years of stability

Queson 16 Unless central mass – yield You recommend: of bronch low. Yield of FNA high (80% but A. Bronchoscopy with 20% risk of PTX); B. PET scan harder if close to diaphragm! C. Repeat Chest CT in 6 months D. Transthoracic needle aspirate E. Surgical resection

Too small (1 cm is quoted size cut-off, we see + at 8mm), though if < 1 cm and neg, more false neg, still need to follow

76 Solitary persistent GGO “Sub-Solid Nodules is oen BAC (“adenocarcinoma in situ”) Naidich DP et al. Recommendations for the Mangement of Subsolid Pulmonary Nodules Detected at CT: A Statement from the Fleischner Society”. Radiology 2013;266:304. PURE GGO § < 5 mm no f/u § > 5 mm, CT scan at 3 months (many disappear), then if no change CT scan q 1 year x 3 years MIXED GGO & solid § CT scan 3 months, if persistent à esp. if solid Smoking history less important component is > 5 mm: think cancer!

Screening for Lung Cancer

n Know criteria from National Lung Screening Trial: • Age: 55-74 • Smoking: 30 pk years • Quit < 15 years n Positive LDCT = > 4 mm nodule n 20% decrease in lung cancer deaths

77 The End!

Extra Quesons for fun at home… Queson A.

50 year old man presents for evaluation of a nonproductive cough and chest pain increasing for the past 3 months. He denies weight loss but notes weakness. Exam reveals a mild bilateral ptosis and is otherwise normal. Labs: mild normocytic anemia.

78 Chest X-ray

Lateral Chest X-ray

79 Chest CT Scan

Queson A

What is the most likely diagnosis? A. Bronchogenic cyst B. Intrathoracic thyroid C. Lymphoma D. Teratoma E. Thymoma

80 Queson A

What is the most likely diagnosis? A. Bronchogenic cyst B. Intrathoracic thyroid C. Lymphoma D. Teratoma E. Thymoma

Mediasnal Masses Differenal Diagnosis First, localize to anterior, middle, or posterior mediastinum Anterior Mediastinum Middle Posterior “The 4 Ts” Bronchogenic cyst Neurogenic cyst Thymoma Pericardial cyst Esophagus Thyroid Lymph nodes Teratoma “Terrible” lymphoma

81 Thymomas

Pearl: Disease of “35s” #1 anterior mediastinal mass in those > 35 35% are malignant 35% are associated with myasthenia 35% have a paraneoplastic syndrome -Pure red blood cell aplasia -Hypogammaglobulinemia -Cushing’s syndrome

Queson A

What is the most likely diagnosis? A. Bronchogenic cyst B. Intrathoracic thyroid C. Lymphoma D. Teratoma Asymptomatic E. Thymoma until infected

All anterior mediastinal, but most have CT scan characteristics; clue here was anemia, myasthenia symptoms

82 Queson B

52 year old man with alcoholic cirrhosis with prior variceal bleeding has new onset of dyspnea x 3 days. Denies chest pain, fever, or sputum production. Has gained 5 pounds over the past month.

Meds: propranolol.

Chest X-ray

83 Lateral Decubitus

Right side

Queson B Thoracentesis reveals a transudate. What is the optimal management in this case? A. Large volume thoracentesis B. Chest tube insertion C. Pleurx catheter insertion D. Pleurodesis E. Diuretics

84 Queson B Thoracentesis reveals a transudate. What is the optimal management in this case? A. Large volume thoracentesis B. Chest tube insertion C. Pleurx catheter insertion D. Pleurodesis E. Diuretics

Pleural Effusions in Paents with Liver Disease n Hepatohydrothorax: Effusions usually when ascitic fluid is present, but not always n Fluid passes from peritoneum to pleural space via diaphragmatic pores & possibly lymphatic channels. Negative pleural pressure draws fluid up. n Fluid is transudative with very low protein n Typically free-flowing

85 Pleural Effusions in Paents with Liver Disease n Management: decrease ascites formation • Low salt diet • Diuretics • TIPS if refractory

Queson B What is the optimal management in this case? Just keeps A. Large volume thoracentesis draining; B. Chest tube insertion reserve large volume C. Pleurx catheter thoracentesis D. Pleurodesis for acute dyspnea relief E. Diuretics

Can’t get pleural surfaces to meet

86 Queson B cont’d What is preferred management for malignant pleural effusions? Pleurx catheter vs. Pleurodesis

Institution dependent, tend to favor Pleurx for shorter length of stay, comfort

87