Download CSIM – 3 things not to miss in Respirology 13:00

CSIM – 3 things not to
miss in Respirology
13:00-16:00
Meredith Chiasson, MD, FRCPC
Respirologist, Department of Medicine
Assistant Professor, Capital Health (Nova Scotia)
Associate Staff, University Health Network (Ontario)
October 14, 2015
Disclosure of Potential for
Conflict of Interest
• No disclosures
Learning Objectives
• Identify and start initial management of drug
induced interstitial lung disease
• Identify and start initial management of
immunocompromised patients with
opportunistic infections
• Identify and start initial management of
pulmonary embolisms, submassive with RV
strain
Identify and start initial management
of drug induced interstitial lung
disease
Case
• 29yo female, non-smoker
• “unresolving pneumonia” with SOB & cough
unresponsive to 3 courses of antibiotics over a
period of 2 months.
• PMHx: ulcerative colitis. No previous
respiratory history.
• MEDICATIONS: 5-ASA
• ALLERGIES: none
5-asa (pneumotox)
Bronchoscopy (lavage) – 56% eosinophils
Drug Induced ILD
Which drugs?
• www.pneumotox.com
• Common culprits (MTX, Amiodarone,
Nitrofurantoin, Bleomycin)
• Be vigilant!
ILD - Classification
Known etiology:
• Drug induced
• Pneumoconiosis
• Hypersensitivity
pneumonitis
• Post infectious
Unknown etiology:
• Sarcoid
• CTD related
• Major IIPs
– IPF (UIP)
– Idiopathic NSIP
– RB-ILD
– DIP
– COP
– AIP
• Rare IIPs
– Idiopathic LIP
– pleuroparenchymal fibroelastosis
ATS & ERS, 2013
• Unclassifiable IIPs
Presentation
History:
• Insidious onset
• Shortness of breath
• Cough (dry in the beginning, then can develop
traction bronchiectasis and productive cough)
• Exercise intolerance
Physical exam:
• Depends on the ILD that is developing
• Velcro crackles – usually basal (NSIP, UIP)
All good, but…..
• ?? Not even thinking about drug induced ILD
• Anyone with NEW SOB +/- cough that is
persisting over months should have CXR +
full PFTs (early ILD may only have ↓DLCO)
regardless of what you hear on exam (how
do I know how many rock concerts you have
been to?)
• May need CT thorax
• Should not need lung biopsy
Screening?
• There is evidence that pts with
pre-existing ILD may be at
increased risk of worsening ILD
with the start of amiodarone,
methotrexate
• Baseline CXR recommended
• High amounts of FiO2 can
potentiate worsening of ILD in
those on Amiodarone &
bleomycin
Am Fam Physician. 2000 Oct 1;62(7):1607-1612
No screening….. but
• Routine screening not
recommended: pulmonary
toxicity can be acute in
onset
• Do not be falsely lulled by
the normal CXR or PFT
from 6 months ago
• Any SOB +/- cough needs
to be investigated
Can Respir J v.16(2); 2009 Feb
PFT - ILD
ILD on imaging, now what??
• Any patient with newly diagnosed ILD needs a
thorough medication review
www.pneumotox.com
• Pattern on CT = known pattern caused by
drug… strongly consider stopping the drug
• Most literature states that the drug should be
stopped and steroids started.
Summary
• Be aware of which drugs have the highest risk
of ILD associated with them. Consider using a
different medication if the patient already has
ILD (do baseline CXR)
• Any patient with non-resolving SOB +/- cough
deserves a CXR and PFTs
• If there is an ILD pattern do a thorough
medication review & strongly consider stopping
the drug
• Prednisone should be used as needed.
Identify and start initial management
of immunocompromised patients
with opportunistic infections
Case
• 58yo woman with recurrent pneumonia (CXR
confirmed)
• Staphylococcus aureus grown from
bronchoscopy
• Work up for immunodeficiency revealed an IgG2
deficiency
• SCIVIg started with resolution of the
pneumonias (>1 year)
Who is at risk?
• Primary (>100):
– Structural (cyliary dysfunction)
– Humeral (B cell, T cell, complement..)
• Secondary:
– Infections (HIV)
– Drugs (Corticosteroids, Azathioprine, MTX,
cyclosporine, tacrolimus, biologics, etc)
– Medical condition (Cancer, Diabetes, asplenia)
Merck, online – Accessed October 10, 2015
Symptoms
• Recurrent infections (upper or lower
respiratory tract).
• May also get recurrent infections of the mouth,
eyes, & digestive tract.
• Thrush
• Fevers, chills, weight loss
Medscape, April, 2015
Risk from medications
• Neutropenia: bacterial, yeast & fungal infections
• Corticosteroids: bacterial, PJP, nocardia, VZV
• Inhaled corticosteroids: thrush, community
acquired pneumonia
• TNF inhibitors: TB, NTM (MAC), HSV
encephalitis, histoplasmosis, listeria
Medscape, April, 2015
Work up for suspected immunodeficiency
• B cells:
– Ig levels (IgG subclass levels)
– Isohemagglutinins
– Lymphocyte subpopulations (CD19/CD20)
– Antibody production (pneumococcus, tetanus)
• T cells:
– Lymphocyte subpopulations
– Delayed-type hypersensitivity reactions
– Mitogen-stimulation assays
• Phagocyte numbers/function:
– Absolute neutrophil count
– CD11a, CD11b, CD11c, CD18 beta receptor
– Assay for chronic granulomatous disease
• Complement status:
– C3/4
Medscape, April, 2015
Work up for suspected immunodeficiency
• Pulmonary function
– Asthma
– COPD
• Radiology:
– CXR
– CT thorax
Medscape, April, 2015
IgG subclass deficiency
• Consider if recurrent chest & sinus infections
• IgG may be normal in the situation of a subclass
deficiency
• IgG2 is the most common deficiency in adults
• Usually well in between episodes of infection
• Can present with bronchopneumonia,
bronchiectasis, bronchitis, obstructive lung
disease, & hyper-reactive airways (" asthma.“)
Agarwal S. Ann Allergy Asthma Immunol. 2007 Sep. 99(3):281-3
Yong PF. Immunol Allergy Clin North Am. 2008 Nov. 28(4):691-713
IgG sublclass - Treatment
• Treat the acute infection with antibiotics (S
pneumonia & H influenzae)
• Prophylax with IgG replacement.
• Prevent or treat pulmonary disease
PJP (causing PCP)
Who is at risk?
• Drugs (immunosuppressants)
• Infections (HIV)
Prophylaxis (PJP) – Septra M-W-F
Prednisone Monotherapy:
• >20mg/day x ≥4 weeks
≥ immunosuppressants:
• Imuran, MTx..
HIV:
• When CD4<200 cells/mm3, or if history of
oralpharyngeal candidiasis
• Alternative: Dapsone
PCP - symptoms
• Progressing over weeks to months (slower in
HIV)
– SOB
– Cough
– Fever
– Physical exam may be normal or may have
fine crackles
PCP
Treating PCP (Moderate-severe)
Preferred Therapy (21 days)
• TMP-SMX: (TMP 15–20mg, SMX 75–100mg/kg/ day
IV q6h or q8h, switch to PO after clinical improvement.
• If PaO2<70mmHg, then add corticosteroids.
Alternative Therapy:
• Pentamidine 4 mg/kg IV daily (over min 60 mins; can
use 3 mg/kg IV daily because of toxicities.
• Primaquineb 30 mg PO daily + Clindamycin IV 600
q6h or 900 mg q8h or po 450 mg q6h or 600 mg q8h]).
http://aidsinfo.nih.gov/guidelines on 10/7/2015
Treating PCP
Mild to Moderate PCP (21 days):
• Preferred Therapy:
• TMP-SMX: (TMP 15–20 mg/kg/day, SMX 75–100
mg/kg/day), PO in 3 divided doses
• TMP-SMX DS - 2 tablets TID.
• Alternative Therapy:
• Dapsoneb 100 mg PO daily + TMP 15 mg/kg/day PO
(3 divided doses)
• Primaquineb 30 mg (base) PO daily + Clindamycin
PO (450 mg q6h or 600 mg q8h)
• Atovaquone 750 mg PO BID with food
Adjunctive Corticosteroids
• Moderate - Severe PCP:
– PaO2 <70 mmHg at room air or
• Dosing Schedule:
• Prednisone (start w/in 72 hrs of PCP therapy):
• IV methylprednisolone can be given as 75% of
prednisone dose
http://aidsinfo.nih.gov/guidelines on 10/7/2015
Summary
• Think of immune system defects in patients with
recurrent infections (IgG subclasses)
• Treatment is to reduce the immunosuppression
as able, treat the infection at hand, correct the
underlying defect if able.
• Be vigilant for PCP, treat aggressively & ensure
you prophylax if ongoing risk
Identify and start initial management
of pulmonary embolisms,
submassive with RV strain
Case
• 49yo man with acute onset SOB and pleuritic
chest pain
• SpO2 92% (R/A, at rest), HR 120, RR 24, BP
108/70, afebrile
• Nil on physical exam, save desaturation to the
mid 80’s with minimal movement.
• Nil on blood work or CXR
What next?
• CT thorax showed saddle embolus with
evidence of RV strain
Do you or do you not thrombolise?
Criteria for lysis?
• Is it only patients with refractory hypotension
and hypoxemia??
Submassive PE’s
Acute PE w/o hypotension (SBP>90 mmHg) & either
1. RV dysfunction (≥1):
– RV dilation or systolic dysfunction on echo
– RV dilation on CT
– ↑BNP(>90pg/mL) or N-term pro-BNP (>500pg/mL)
– ECG (new complete/incomplete RBBB, antero
septal ST ↑/↓, or anteroseptal T-wave inversion)
2. Myocardial necrosis:
– ↑ Tn I (>0.4 ng/mL) or Tn T (>0.1 ng/mL)
Circulation, 2011; 123: 1788-1830
Submassive PE
• If normotensive <3% mortality (therefore not
going to see mortality benefit even if lysis very
effective)
• Better RVSP, 6MWD, NYHA when treated with
Alteplase
Circulation, 2011; 123: 1788-1830
Who might benefit from lysis?
Circulatory or respiratory insufficiency:
• ↓BP (ever) or Persistent shock index (HR/SBP >1)
• SpO2<95% (R/A) + resp distress or BORG>8
Evidence of moderate/severe RV injury:
• Echo: RV hypokinesis, McConnell’s sign (RV akinesis
of mid free wall, normal motion at apex), inter
ventricular septal shift/bowing, or RVSP 40 mmHg.
• Biomarker: major elevation of Tn or BNP
Low bleeding risk
Circulation, 2011; 123: 1788-1830
Summary
• Lyse massive PE’s (hemodynamic instability)
• Lyse submassive PE’s with cardiovascular or
respiratory compromise with high risk of poor
long term outcome, if low bleeding risk (still
controversial)
• Ongoing studies looking at lysis (systemic and
catheter based) for submassive PE’s
ENJOY PEI
References
• Circulation, 2011; 123: 1788-1830
• http://aidsinfo.nih.gov/guidelines on 10/7/2015