Transcript Pulmonary Issues - Scleroderma Association of Manitoba

Living with Pulmonary Fibrosis
Gerard Cox
FIRH – SJHH
McMaster University
Sept 2013
What is pulmonary fibrosis?
Interstitium
• Literally what is between (air)spaces
– Alveolar walls
– Walls of lobules = septae (septal lines)
– Lymphatic vessels
• Bronchovascular tissues
– Blood vessels
– Airways
• Fissures
Anatomy Lung: Alveoli-Interstitium-Vasculature
Collagen network in the lung
Lung collapsed
Lung inflated
Toshima et al, ArchHistolCytol 2004
What is Pulmonary Fibrosis?
• Scarring of the lung
• Interstitial
• Idiopathic
Characteristics of ILD
• Sub-acute to chronic
• Interference with lung function
– Airways less involved (↓FEV due to ↓VC)
– Stiffer lungs = lower VC
– Blocked blood vessels = impaired oxygenation
• Symptoms
– Stiff and small lungs = dyspnea
– Cough
• Sputum – less frequent (no bronchitis)
• Pain – no pain receptors in lung tissue
How to Recognize ILD
• Symptoms
– Chronic, non-variable, (dyspnea and cough)
• Signs
– Bilateral basal crackles (cave sine)
– Clubbing (<25%)
• Radiology
– Increased markings (linear or nodular)
• Breathing test results
– Small lungs, no obstruction, ↓gas exchange
Pulmonary Function
• Small lungs
↓ TLC and ↓ VC
• No obstruction
↓ FEV ≡ ↓ VC
• ↓ Gas exchange
↓ Diffusing capacity
↓ SpO2
[xs]
• ↓ Exercise capacity
CPET or 6MW
What you need to know
• How you feel
• Vital capacity – expressed as % predicted
• Oxygen – home oximeter
• Exercise capacity
What can I expect
• Diagnosis
• Treatment
• Secondary illnesses
• Lung transplantation
Pulmonary Fibrosis
Diagnostic Process
Is there interstitial lung disease?
Chest Xray – [exclude CHF, trial of diuretic]
High Resolution CT scan – [nature and extent]
Is there impairment?
Pulmonary Function Test - VC, TLC, DCO reduced
Exercise Test - cardiopulmonary, O2, tolerance
Is it getting worse? [?MCID? and ?Interval?]
Symptoms, Radiology, Physiology
Pulmonary Fibrosis in SSc
Diagnostic Process
If there is interstitial lung disease:
- typical (NSIP or UIP)
- due to another cause
Does it need to be treated?
Can it be treated? - Risk/Benefit
(Risk = 25% incidence of serious side-effect)
Management - ?2’ary?
Is disease present?
Typical or not?
Is it causing a problem?
Is it getting worse?
Primary (idiopathic) or
secondary?
Remove cause or
Treat =
immunosuppression
Clx, Xray, HRCT, PFT
Ditto
Symptoms, PFT, CPET
Change in Sx or tests
History, blood tests
Drugs, dusts, GERD
Cyclophosphamide
or Azt or MMP +/- pred
Organ Specific Mortality
Treatment of PF in SSc
• CYC has been shown to be superior to
placebo in SSC-ILD ….D Khanna
– Clin Exp Rheum 2010;28:S52-S62
• 2 prospective randomized studies failed to
show a major benefit …. Bussone G
– Autoimmunity Reviews 2010
Scleroderma-Related
Interstitial Lung Disease (ILD)
• Pulmonary involvement, including ILD and pulmonary HTN,
develops in 80% of patients with SSc, and is currently the leading
cause of death in these patients
• 40% of all patients with SSc develop moderate restrictive ventilatory
impairment, and 15% develop severe restrictive associated with a
10-year survival rate of only 40-50%
• NSIP is much more prevalent (76%) than UIP (11%) in SScassociated ILD – COP, CLP, PVOD, HsPn
• NSIP has a longer course, lower rate of decline in pulmonary
function and a better response to therapy than UIP (non-SSc)
Treatment of SSc-Related ILD
• Collagen accumulation results from abnormal interactions between
endothelial cells, mononuclear cells leading to production of fibrosisinducing cytokines and stimulation of fibroblasts
• Maybe vascular hyperreactivity, obstruction and tissue hypoxia
Beware
of using steroids alone
• Inflammatory cells in BAL fluid in SSc-ILD reflects inflammation in
the lungs - ?pathogenic?
• Corticosteroids and immunosuppressive therapy have been used to
treat SSc-associated ILD
• No documented efficacy of corticosteroids in placebo-controlled
trials: concerns of an increased risk of scleroderma renal crisis
(Steen et al. Arthiritis Rheum 1998 41: p1613-19)
Adverse Events
Table 3
Change in Values from Baseline to Month 12
Table 2
Absolute
difference in
TLC (4.09;
p=0.026)
favoring CYC
TDI improved
by 1.4±0.23 in
CYC group and
worsened in
placebo group 1.5±0.43
(p˂0.001)
Absolute
Difference in
FVC (2.53%;
p˂0.03)
favoring CYC
Absolute
difference in
HAQ-DI (-0.16;
p=0.009)
favoring CYC
Combined
endpoint of time
to death plus
FVC at 12
months favoring
CYC (p=0.04)
Adjusted FVC at 24 Months
P=0.364
Tashkin et al. Am J Respir Crit Care Med 2007 176: p1026-1034
Adjusted Mahler TDI at 24 Months
P=0.074
Tashkin et al. Am J Respir Crit Care Med 2007 176: p1026-1034
Adjusted Rodnan Skin Score
at 24 Months
P=0.23
Tashkin et al. Am J Respir Crit Care Med 2007 176: p1026-1034
What that means is…
• Little or no prednisone
• Cyclophosphamide slows deterioration
• If not tolerated, try another drug
• You never know…..
HRCT – BW - 2006
HRCT – BW - 2007
2011
2013
Lung transplantation
• Before kidney
• 3 – 6 months to assess
• 10% per yr
GERD and PF
• Pepsin and bile salts
• Found in BAL
• Reported in patients post-transplant
– Associated with rejection
• Frequently found
• Abstract at ATS 2011
Assymmetric PF
• Tcherakian et al
• Thorax 2011;66:226-231
• Progression of IPF: lessons from
asymmetric disease
• 32 vs 64 matched controls; R>L ⅔
• GERD 62 vs 31%
• Acute exacerbations 47 vs 17%
• Similar survival (!)
JC
JC
JC
JC
Pulmonary Hypertension
• Screen (CSRG)
• Wonder if declining function but breahing
tests stable
• Definitive test - catheterization
• Treat – benefits
• Seek specialized care
Where are we now?
• More aware – community + medics
– Advocacy, SSO, CSRG data
• Multi-disciplinary teams – Rheumatology+
– Kidney, heart, stomach, lung
• New drugs
– GI, pirfenidone,
• We are in this together
VC
VC
VC
VC