Collagen vascular disease in the lungs

COLLAGEN VASCULAR
DISEASE IN THE LUNGS:
CURRENT VIEWS
Gillian Ainslie
UCT Lung Institute &
Respiratory Clinic, Groote Schuur Hospital

Screening for Lung Disease in CVD
Should be routine
• lung disease in CVD very common (20-85% in diff diseases & series)
• major prognostic role
• can pick up early potentially treatable disease
• to have baseline if using potentially toxic drugs
Methods:
• Clinical
• Imaging (CXR, HRCT)
• PFTs
• Lung biopsy (TBLBx, SLBx)

Forms of Lung Disease in CVD
• Interstitial (ILD) e.g. NSIP, UIP, LIP, DIP, AIP, OP
• Airways e.g. bronchiectasis, bronchiolitis
• Vascular e.g. pulm hypertension, PTE, alveolar
haemorrhage
• Pleural e.g. effusions, thickening
• Muscular/diaphragmatic e.g. restriction,
atelectasis, Shrinking Lung Syndrome

Wells. Sem Resp Crit Care Med 2007; 28: 379-88

ILD IN COLLAGEN
VASCULAR DISEASE
(CVD)

CXR Infiltrates in CVD
Causes other than CVD-ILD:
• Infections
• bacterial
• PCP
• fungal
• Aspiration (esp. SSc, PM/DM)
• Fluid overload
• cardiac
• renal
• Drug reactions
• methotrexate (0.5-12% of RA patients)
• cyclophosphamide
• MoAbs
• Malignancy
• Lung cancer (esp. BAC)
• Lymphoma ( esp. NHL)

Antoniou et al. ERJ 2009; 33: 882-96

Kim et al. Chest 2009; 136: 1397-1405

NSIP: CXR
• Bilateral
• Fine reticular
• Ground glass

UIP: CXR
• Bilateral
• Mainly reticular
• Mainly basal
• Peripheral
• Volume loss

HRCT: UIP vs. NSIP

Kim et al. Chest 2009; 136: 1397-1405

Mean survivals of patients:
HRCT diagnosis of NSIP: 160 mths
HRCT diagnosis of UIP: 42 mths
NSIP
alt diagnosis
UIP

ILD IN SYSTEMIC
SCLEROSIS (SSc)

Background
ILD common in SSc: 75% (significant in 25% &
severe in 13%)
>50% have oesophageal abnormality - ? aspiration
role in ILD
Despite better prognosis than IPF, ILD still main
cause of death in SSc
Difficult to predict the minority with progressive
disease
Most likely to deteriorate in first 4 yrs of
presentation
Antoniou et al. ERJ 2009; 33: 882-96

Background
Has better prognosis than IPF:
NSIP more common than UIP
SSc-UIP has better prognosis than IPF
Antoniou et al. ERJ 2009; 33: 882-96
Kim et al. Chest 2009; 136: 1397-405
Park et al. AJRCCM 2007; 175: 705-11

CXR
Limited value
Imaging
HRCT
Very sensitive (25-50% abnormal in diff series)
NSIP pattern commonest
Good correlation with pathology (although GGO can occur
with fine fibrosis, esp. if traction bronchiectasis)
Extent of disease (but not GGO) good predictor of outcome
Often very limited disease (mean 13% of lung volume, esp. in
lower 1/3 of lungs)
HRCT: 50% of those with GGO HC over 5 yrs, rest stable
Antoniou et al. ERJ 2009; 33: 882-96
Desai et al. Radiology 2004; 232: 560-7
Launay et al. J Rheum 2006; 33: 1789-801
Devaraj et al. Sem Resp Crit Care Med 2007; 28: 389-97

FVC
• in 25% of SSc
Baseline PFTs
• in FVC

Serial PFTs & Prognosis: IPF
Bad Prognostic Factors:
• DLCO >15% on 12 mths FU
• FVC >10% on 6 & 12 mths FU
>2x t
Latsi P et al. AJRCCM 2003; 168: 531-7
Collard H et al. AJRCCM 2003; 168: 538-42
Flaherty K et al. AJRCCM 2003; 168: 543-8
Jegal Y et al. AJRCCM 2005; 171: 639-44

Serial PFTs: SSc-ILD
Must exclude other causes of PFTs:
• muscle
• joint
• cardiac
• pleural
• COPD
• drug reactions
May need to correlation with ILD on HRCT
mortality if DLCO at 3 years (indolent disease)
DLCO & FVC over time: indication to Rx
Serial FVC more reliable than DLCO (Rx studies)
Gilson et al. ERJ 2010; 35: 112-7
Bouros et al. AJRCCM 2002; 165: 1581-6
Wells. Sem Resp Crit Care Med 2007; 28: 379-88

Prognostic Algorithm
Used 215 SSc-ILD patients to
construct a prognostic algorithm
integrating PFTs & HRCT
? more accurate than either alone
Goh et al. AJRCCM 2008; 177: 1248-54

Prognostic Algorithm
Easy to apply in clinical practice
Still needs to be validated
HR 3.5 vs. 2.5 (HRCT)or 2.1 (FVC)
Goh et al. AJRCCM 2008; 177: 1248-54

6MWT & Prognosis: IPF
• Safe
• Simple, convenient & inexpensive
• Reproducible
• Strong & independent predictor of survival time
• NB. desaturation to

SSc: 6MWT
Conflicting data on reproducibility
Prognostic value unproven
Wells. Sem Resp Crit Care Med 2007; 28: 379-88
Khanna et al. Curr Rheum Rev 2010; 6: 138-44

SSc: Exercise Testing
CPEX has been validated:
>2x t
Swigris et al. Thorax 2009; 64: 626-30

Seldom needed
Lung Biopsy
• HRCT predictive of pathology
• little difference in 5YS UIP (82%) vs. NSIP (91%)
Antoniou et al. ERJ 2009; 33: 882-96
Bouros et al. AJRCCM 2002; 165: 1581-6
Park et al. AJRCCM 2007; 175: 705-11

Therapy
1) Prednisone
?? renal crisis if use >15mg/day of prednisone (Steen)
Usually only if severe skin disease (DeMarco)
But can occur even on low doses (7.5mg)
2) Cyclophosphamide
Has best data (SLS) *
Usually only achieves stabilisation of PFTs & symptoms
Awaiting data:
• Mycophenolate mofetil
• Anti-IL13
• Tyrosine kinase inhibitors (Imatinib, Dasatinib)
Ineffective :
• Bosentan (BUILD-2)
Antoniou et al. ERJ 2009; 33: 882-96
Khanna et al. Curr Rheum Rev 2010; 6: 138-44

Scleroderma Lung Study
158 SS patients, FVC m 68% pred, DLCO m 47% pred
Cyclophos vs. P x 1 yr
1 yr: mean diff FVC 2.5 % pred. C vs. P (95% CL 0.28 - 4.79 %, p

RHEUMATOID
ARTHRITIS (RA)

Background
ILD prevalence in RA very variable: 7-68%
Lung disease causes 10-20% of deaths in RA
ILD may coexist with airways disease
Antoniou et al. ERJ 2009; 33: 882-96
Kim et al. ERJ 2010; 35: 1322-8

RA-ILD worse prognosis than other CVD-ILD:
UIP more common than NSIP in RA
RA-UIP similar prognosis to IPF
Bad Prognosis:
• UIP pattern on HRCT
• if lung disease presents early
• younger patients
• smokers
Kim et al. Chest 2009; 136: 1397-405
Kim et al. ERJ 2010; 35: 1322-8

Imaging
UIP
CXR
Limited value
HRCT
Very sensitive (19-56% of RA)
Good predictor of pathology
Patterns:
• UIP (commonest): peripheral reticular + HC
• NSIP: reticular + GGO
• OP (organising pneumonia): patchy GGO
May see coexisting airways disease
NSIP
OP
Antoniou et al. ERJ 2009; 33: 882-96
Akira et al. JCAT 1999; 23: 941-8
Tanaka et al. Radiology 2004; 232: 81-91
Devaraj et al. Sem Resp Crit Care Med 2007; 28: 389-97

PFTs
Good at picking up lung disease
• FVC
• DLCO
• most sensitive
•

Lung Biopsy
Seldom needed
HRCT predictive of pathology & prognosis
May do if atypical or suspect OP:
Plugs of loose proliferating granulation
tissue (“Masson bodies”) within lumen of
bronchioles (“bronchiolitis obliterans”) &
extending into alveolar ducts & spaces
(“organising pneumonia”)
Patchy distribution (often peribronchial)
Normal lung architecture
Antoniou et al. ERJ 2009; 33: 882-96

Therapy
No randomised controlled trials, thus empiric use
1) Prednisone
Not useful in UIP but very effective in OP:
• Most are steroid sensitive, usually within days
• Prednisone (0.5-1mg/kg) x 1-3 months, then 10-20mg daily/alternate
daily x 6-12 mths
• Good prognosis but can relapse
2) Immunosuppressive Rx
• Azathioprine
• Cyclophosphamide
• Methotrexate
• Cyclosporin A
• MoAbs (esp. Infliximab)
NB. can cause hypersensitivity pneumonitis
Antoniou et al. ERJ 2009; 33: 882-96

SYSTEMIC LUPUS
ERYTHEMATOSUS
(SLE)

ILD uncommon in SLE:
Background
• Chronic interstitial pneumonia (CIP): 3-8%
• Acute lupus pneumonitis (ALP): 1-4%
• Diffuse alveolar haemorrhage (DAH): 50%)
CIP ALP DAH
Antoniou et al. ERJ 2009; 33: 882-96

HRCT
More sensitive than CXR
CIP:
Imaging
Can pick up mild changes in 1/3
Poor correlation with clinical S&S, CXR & PFTs
Patterns:
• NSIP + interlobular fissure thickening, esp. basal: commonest
• OP
• LIP
• Shrinking Lung Syndrome
ALP & DAH:
Similar pattern: patchy GGO esp. LZs
? resolves to NSIP
Antoniou et al. ERJ 2009; 33: 882-96
Fenton et al. AJR 1996; 166: 301-7
Bankier et al. Radiology 1995; 196: 835-40
Devaraj et al. Sem Resp Crit Care Med 2007; 28: 389-97

Lung Biopsy
Not often done
CIP:
NSIP pattern: non-specific interstitial
mononuclear infiltration & fibrosis
ALP:
Non-specific DAD with necrosis, hyaline
membranes, haemorrhage & cellular
infiltrate
DAH:
Neutrophilic capillaritis
Antoniou et al. ERJ 2009; 33: 882-96
Devaraj et al. Sem Resp Crit Care Med 2007; 28: 389-97

Therapy
Empiric
1) ALP:
Pulse medrol x 3 days ± cyclophosphamide
2) DAH:
Pulse medrol x 3 d ± cyclophosphamide ± plasmaphoresis
3) CIIP:
Prednisone ± azathioprine or cyclophosphamide
Antoniou et al. ERJ 2009; 33: 882-96

Pulmonary Approach to CVD Patients
Kim et al. Chest 2009; 136: 1397-1405