Table 2.
Adjusted Cox regression models to determine the association of pulmonary IPF microbiome to disease progression defined as death, acute exacerbation, lung transplant, or decline in FVC of 10% or DLCO of 15%. In model 2A, microbiome is represented in the model by Principal Components (PC) 1 and 2*. In model 2B, the strongest drivers of PC1 and PC2, Streptococcus OTU 1345 and Staphylococcus 1348 represent the microbiome component of the model. In model 2C, as opposed to using the relative abundance of Streptococcus and Staphylococcus as continuous covariates as was done in 2B, we determined thresholds for the relative abundance of Streptococcus OTU 1345 and Staphylococcus 1348 that simulataneously optimized the model. This approach best optimizes the model as is indicated by the index of concordance.
| Table 2A. | |||
|---|---|---|---|
| Variable | Relative Risk | 95% Confidence Interval | P-value |
| Age (per 10 years) | 0·83 | 0·.41,1·67 | 0·60 |
| Male | 0·70 | 0·30,1·65 | 0·42 |
| Ever Smoker | 2·20 | 0·89,5·40 | 0·09 |
| FVC (per 10%) | 1·26 | 0·92,1·73 | 0·14 |
| DLCO (per 10%) | 0·87 | 0·52,1·46 | 0·59 |
| Desaturation <88% | 4·18 | 1·4,12·42 | 0·01* |
| Gastroesophageal reflux | 3·05 | 1·19,7·83 | 0·02* |
| Principal Component 1 | 1·80 | 1·21,2·68 | 0·003* |
| Principal Component 2 | 1·72 | 1·16,2·56 | 0·007* |
| Shannon Diversity Index | 0·67 | 0·44,1·01 | 0·06 |
| Concordance Index | 0·71 | ||
| Table 2B. | |||
|---|---|---|---|
| Variable | Relative Risk | 95% Confidence Interval | P-value |
| Age (per 10 years) | 0·82 | 0·41,1·64 | 0·57 |
| Male | 0·72 | 0·31,1·69 | 0·45 |
| Ever Smoker | 2·17 | 0·89,5·32 | 0·09 |
| FVC (per 10%) | 1·27 | 0·93,1·74 | 0·13 |
| DLCO (per 10%) | 0·87 | 0·52,1·47 | 0·61 |
| Desaturation <88% | 4·33 | 1·44,12·95 | 0·009* |
| Gastroesophageal reflux | 3·05 | 1·19,7·82 | 0·02* |
| Streptococcus OTU 1345 % relative abundance | 1·11 | 1·04,1·18 | 0·0009* |
| Staphylococcus OTU 1348 % relative abundance | 1·16 | 1·03, 1·31 | 0·01* |
| Shannon Diversity Index | 0·68 | 0·45,1·02 | 0·06 |
| Concordance Index | 0·72 | ||
| Table 2C. | |||
|---|---|---|---|
| Variable | Relative Risk | 95% Confidence Interval | P-value |
| Age (per 10 years) | 0·71 | 0·35, 1·43 | 0·33 |
| Male | 0·87 | 0·36, 2·12 | 0·77 |
| Ever Smoker | 1·54 | 0.67, 3·52 | 0·31 |
| FVC (per 10%) | 1·30 | 0·94, 1·79 | 0·11 |
| DLCO (per 10%) | 0·99 | 0·60, 1·64 | 0·99 |
| Desaturation <88% | 7·13 | 2·25, 22·5 | 0·0008* |
| Gastroesophageal reflux | 3·41 | 1·28, 9·08 | 0·01* |
| Streptococcus OTU 1345 >threshold (3.9% relative abundance) | 10·19 | 2·94, 35·35 | 0·0002* |
| Staphylococcus OTU 1348 >threshold (1.8% relative abundance) | 5·06 | 1·71,14·93 | 0·003* |
| Shannon Diversity Index | 0·53 | 0·33, 0·84 | 0·007* |
| Concordance Index | 0·77 | ||
Prior to building these models, in order to identify OTUs associated with disease progression, we first conducted Cox regression analyses adjusted for factors known to influence survival: age, gender, smoking status and desaturation during six minute walk testing. Forty-three OTUs met p<0·10 significance in a Cox proportional hazards analysis associated with the combined endpoint. These OTUs were then used to construct principal components.