ILD-TRACK: Interstitial Lung Disease Progression Tracker

Background

Autoimmune-associated ILD affects 25-80% of SSc patients, 10-60% of RA patients, and up to 80% of patients with inflammatory myopathies (particularly anti-MDA5+). Serial PFTs are the cornerstone of monitoring, but raw FVC/DLCO values without trajectory modeling leave clinicians without predictive insight.

Mathematical Framework

Annualized Slope Estimation

Given n PFT measurements $(t_i, y_i)$ where $y_i$ is FVC or DLCO percent predicted:

$$\hat{\beta} = \frac{\sum_{i=1}^{n}(t_i - \bar{t})(y_i - \bar{y})}{\sum_{i=1}^{n}(t_i - \bar{t})^2}$$

Disease-Specific Decline Rates

Risk-Adjusted Projection

$$FVC_{projected}(t) = FVC_{baseline} + (\mu_{decline} \times R \times (1 - T)) \times t + \epsilon$$

Where $R = \prod_{k} r_k$ (risk multiplier product) and $T$ is treatment effect factor.

Monte Carlo Uncertainty

For each of 5,000 simulations: $$\text{rate}$$i \sim \mathcal{N}(\mu{adjusted}, \sigma_{adjusted}) $$FVC_i(t) = \max(0, FVC_{baseline} + \text{rate}_i \times t)$$

95% CI from 2.5th and 97.5th percentiles of the empirical distribution.

Treatment Effect Evidence

• Nintedanib: 44% reduction in FVC decline (SENSCIS, NEJM 2019)
• Mycophenolate: ~50% stabilization (SLS-II, Lancet Resp Med 2016)
• Tocilizumab: ~60% FVC preservation (focuSSced, Lancet 2020)
• Rituximab: ~55% (Md Yusof, Lancet Resp Med 2017)

Pulmonary Hypertension Screening

DLCO/FVC ratio < 0.50 → high risk (DETECT algorithm, Coghlan 2014). Disproportionate DLCO decline relative to FVC suggests pulmonary vascular disease.

Progression Classification (ATS/ERS 2018)

• Rapidly Progressive: FVC decline ≥10%/year
• Progressive: FVC decline 5-10%/year or FVC ≥5% + DLCO ≥15%
• Marginal: FVC decline 2-5%/year
• Stable: FVC change <2%/year

Implementation

Pure Python (stdlib only). Supports 6 ILD subtypes, 7 treatments, 10 risk modifiers. Seeded Monte Carlo for reproducibility.

References

1. Distler O et al. Nintedanib for SSc-ILD. NEJM 2019;380:2518-28.
2. Tashkin DP et al. Cyclophosphamide vs placebo in SSc lung disease. NEJM 2006;354:2655-66.
3. Tashkin DP et al. Mycophenolate vs cyclophosphamide in SSc-ILD. Lancet Resp Med 2016;4:708-19.
4. Khanna D et al. Tocilizumab in SSc. Lancet 2020;395:1407-18.
5. Flaherty KR et al. Nintedanib in progressive fibrosing ILD. NEJM 2019;381:1718-27.
6. Goh NS et al. ILD in SSc: a simple staging system. AJRCCM 2008;177:1248-54.
7. Coghlan JG et al. DETECT study for PH in SSc. Ann Rheum Dis 2014;73:1340-49.
8. Solomon JJ et al. Predictors of mortality in RA-ILD. Eur Resp J 2016;47:588-96.
9. Moghadam-Kia S et al. Anti-MDA5 dermatomyositis. Curr Rheumatol Rep 2016;18:53.