Practical Application: Case Reviews

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Practical ApplicationCase Reviews
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51-Year-Old Man with IPF and Worsening Dyspnea
History

• Obese white male with IPF (thoracoscopic lung
  biopsy)
• Remote smoking history
• Minimal GERD symptoms
• No occupational exposure
• No family history of IPF
• No CTD symptoms

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Tests at Presentation (2005)

• PFTs
• FVC 69 predicted
• TLC 64 predicted
• DLCO 61 predicted
• FEV1/FVC ratio 82
• RA ABG pH 7.42 pCO2 37 mmHg pO2 88 mmHg
• 6MWT desaturation to 91 on room air
• 6MWD 1250 feet
• Echocardiogram normal RV and LV function but
  tricuspid regurgitation inadequate to determine
  RVSP

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HRCT at Presentation
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Clinical Course

• Late 2006
• Initial Treatment pred/AZA, NAC
• Increased dyspnea
• FVC 60 predicted
• DLCO 49 predicted
• Desaturation to 78 on 6MWT
• Therapy with mycophenolate initiated
• 20072008
• PFTs stabilized
• No significant change in dyspnea
• ECHO 1/08 RVSP 44 mmHg
• Bosentan started without improvement,
  discontinued 4/08

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Clinical Course June 2008

• Worsening dyspnea (now at rest) over 2 weeks
• No fever, chills, or night sweats
• Admitted to a local hospital
• O2 saturation 9091 on 100 O2
• BIPAP
• Used to maintain oxygenation
• Initially on room air, later with O2
  supplementation
• Patient remained afebrile over 48h after
  admission
• Blood and sputum cultures negative
• Treatment high dose steroids, diuretics, and
  antibiotics
• Bronchoscopy not performed due to severity of
  illness
• Transferred to regional center on day 9 of
  hospitalization

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HRCT On Admission
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Clinical Course

• Nitric oxide given on day 2 after transfer with
  minimal improvement in oxygenation
• Transplant re-evaluation
• Evaluation completed in 48h
• Double lung transplant 24h later
• Extubated on POD 2
• On room air POD 5
• Back to work in 6 months on room air

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Usual Interstitial Pneumonia
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Explant Lung Pathology
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Potential Patterns of Acute Exacerbation in IPF
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Pathology Summary

• Acute exacerbation in IPF appears to be part of
  the natural history of the disease
• The acute disease usually has features of DAD or
  organizing pneumonia OP tends to be steroid
  responsive
• Acute on chronic lung disease manifestations
  are not restricted to IPF

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Clinical Features of AE of IPF

• May occur at any time during course of IPF
• New or worsening dyspnea within 30 days
  (typically 2-4 weeks)
• Low-grade fever, worsening cough, flu-like
  symptoms
• Presentation with severe hypoxemia and
  respiratory failure

Akira M, et al. Am J Respir. 1997168-179. Ambrosi
ni V, et al. Eur Respir J. 200322821-826.
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Take Home Messages AE of IPF

• Definition clinical worsening (typically over
  2-4 weeks) not associated with an identifiable
  cause
• Deterioration characterized by
• Fever
• Worsening cough, dyspnea, and gas exchange
• New bilateral GGO consolidation on HRCT
• In the absence of a specific diagnosis, pulse
  steroids and broad spectrum antibiotics should be
  considered immunosuppression may be subsequently
  considered
• Patients requiring mechanical ventilation for
  hypoxemic respiratory failure have high mortality
• Transplantation is an option

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66-Year-Old Man with UIP History

• In spring of 2001, increased dyspnea on exertion,
  worse with stairs and minimal dry cough
• Dyspnea not associated with chest pain,
  lightheadedness, dizziness, palpitations, or
  diaphoresis
• Medical History
• Left adrenal mass
• Obstructive sleep apnea
• Insomnia
• Allergic rhinitis
• Coronary artery disease
• Hypertension
• Diabetes
• Tracheostomy at age 7 for strep throat
• RCA stent placement in 1999
• No known allergies

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History

• Family History
• Significant for CAD
• Patient's mother died at age of 79 of CHF
• 1 sibling and 3 children and are healthy, no
  respiratory disease
• Social History
• Patient owns a wholesale bakery
• Very active gardener
• Lately unable to maintain his tomato garden due
  to his lung disease
• Patient denies any smoking history
• Occasional alcohol
• Married for 42 years with 3 adult children
• No pets or birds
• Born and raised in California, lived in the SF
  Bay Area since 1994
• Review of systems
• Symptoms consistent with GERD

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Clinical Course Diagnosis and Treatment

• Patient was evaluated at regional pulmonary
  center February 2004
• Thoracoscopic lung biopsy May 2004
• Pathology consistent with the usual interstitial
  pneumonia (UIP)
• Clinical mild-to-moderate disease, and the
  patient was referred for pulmonary rehabilitation
  
• Initially treated with prednisone and
  azathioprine, but he did not tolerate prednisone,
  ie, weight gain, irritability
• Symptoms progressed despite therapy
• Mycophenolate mofetil initiated April 2005,
  increased to 1.5 g bid prednisone was tapered to
  zero
• Patient has done quite well on mycophenolate
  mofetil
• Stabilization of his PFTs
• Increased energy
• PFTs and HRCT suggest only mild progression of
  disease
• Mr. U had an initial pre-transplant evaluation
  but disease was too mild to become viable LT
  candidate

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Current Medications

• Mycophenolate mofetil 1500 mg bid
• Sulfamethoxazole and trimethoprim 5 days per
  week
• Furosemide 20 mg daily
• Cetirizine 10 mg daily
• Isosorbide 30 mg daily
• Atorvastatin 20 mg daily
• Diltiazem 180 mg daily
• Valsartan 80 mg daily
• Zolpidem 10 mg nightly
• Rabeprazole 20 mg bid
• Aspirin 325 mg daily
• Ibuprofen 200 mg daily
• Acetaminophen 650 mg daily
• N-Acetylcysteine 600 mg tid

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Clinical Course Sleep

• Mr. U. was diagnosed with OSA by a sleep study at
  a community hospital
• Patient likes to sleep on his stomach and has not
  been able to find an acceptable CPAP mask
• Weight loss and nocturnal oxygen saturation study
  recommended

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Clinical Exam

• General Appearance mildly obese
• HEENT
• Normocephalic and atraumatic
• Extraocular movements intact
• Pupils equal, round, and reactive
• Sclerae anicteric
• Oropharynx clear
• Nose was within normal limits
• Neck
• Thick and short, collar size 17
• Supple, no thyromegaly
• Nodes No cervical or axillary lymphadenopathy
• Back No costovertebral angle tenderness
• Lungs
• Bilateral air entry
• Few bibasilar rales

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Clinical Exam (cont)

• Cardiac
• Regular rhythm
• Regular heart rate 100 bpm
• Blood pressure 120/66
• No jugular venous distention
• No murmurs or gallops are appreciated
• Breasts No masses or nipple discharge
• Abdomen
• Soft, obese, and nontender
• Normal bowel sounds present
• No palpable organomegaly
• Extremities
• No cyanosis at rest
• 1 clubbing
• No edema
• Distal pulses were equal and intact
• Neurologic and Psychiatric
• Patient was alert and oriented
• Cranial nerves II through XII intact

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HRCT
8/04
5/09

• Subpleural reticulation with a basal and
  posterior predominance
• Minimal progression of abnormalities

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Change in HRCT

• Stable enlargement of pretracheal, precarinal,
  and subcarinal lymph nodes
• Lymphadenopathy
• No evidence of axillary or hilar
• Stable mediastinal
• Coronary artery calcification is noted
• No pleural or pericardial effusions
• Re-evaluation of lung parenchyma reveals area of
  subpleural reticulation and ground-glass opacity
  with architectural distortion and traction
  bronchiectasis
• Small hiatal hernia detected no evidence of
  suspicious lytic or sclerotic bony lesions
• Minimal worsening of fibrosis on 5/09 compared
  with 8/04

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Clinical Course

• PFT Interpretation
• Moderate restrictive ventilatory defect
• Severe reduction in DLCO in July 2004
• Improved in 2005
• Progressed in 2009
• ECHO, 3/07
• LVH with normal RV function
• Estimated RVSP-35 mm Hg, mild PH
• Laboratory Data
• Comprehensive metabolic panel, CBC, PT, and INR
  unremarkable
• Only abnormality noted was rheumatoid factor,
  positive (22)

PFT Changes
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Case Summary

• Mr. U is a 66-year-old gentleman with ILD
• Lung biopsy is consistent with UIP, but HRCT and
  clinical course are not typical of IPF
• Ground glass opacities but no honeycombing on
  HRCT
• Initial clinical improvement and then
  stabilization on mycophenolate mofetil
• Non-specific interstitial pneumonia (NSIP) can be
  more responsive to immunosuppressive therapy and
  has a better prognosis than UIP/IPF

Management Plan

• Continue medications
• Mycophenolate mofetil for immunosuppression
• Sulfamethoxazole and trimethoprim DS TIW for PCP
  prophylaxis
• Rabeprazole for reflux
• Repeat sleep study
• Follow-up visit with transplant team in 6 months
• Right heart catheterization to evaluate for
  pulmonary hypertension

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Take Home Messages

• All that is UIP is not IPF
• UIP is a pathological diagnosis, not a clinical
  one
• Need to look at entire body of data, ie, HRCT,
  clinical presentation and response to therapy,
  and progression of disease
• IPF itself is heterogeneous so Mr. U could still
  have an atypical variant of IPF
• Although patients with UIP on biopsy and atypical
  HRCTs are known to have a better prognosis than
  patients with a concordant diagnosis, more
  research and studies are needed to determine the
  prevalence and significance of this entity