Table 2:
Predictors of CLAD development or death in the 500 days after 1-year post-transplant surveillance
| Univariable |
Multivariable |
|||
|---|---|---|---|---|
| HR (95% CI) | p value* | HR (95% CI) | p value* | |
| Age, per 1-year increase | 1·00 (0·97–1·03) | 0·91 | ·· | ·· |
| Female sex | 1·62 (0·73–3·61) | 0·24 | ·· | ·· |
| Pretransplant diagnosis | ||||
| Chronic obstructive pulmonary disease | 1 (ref) | ·· | 1 (ref) | ·· |
| Interstitial lung disease | 0·93 (0·42–2·07) | 0·86 | 1·16 (0·42–3·20) | 0·77 |
| Cystic fibrosis | 0·33 (0·09–1·17) | 0·086 | 0·27 (0·07–1·10) | 0·068 |
| Other | 0·44 (0·10–1·95) | 0·28 | 0·68 (0·12–3·68) | 0·65 |
| Double lung transplant | 0·82 (0·37–1·81) | 0·63 | ·· | ·· |
| Mean FEV1, per 1-L increase | 0·81 (0·11–5·98) | 0·83 | ·· | ·· |
| Induction Immunosuppression | ||||
| No induction | 1 (ref) | ·· | 1 (ref) | ·· |
| Basiliximab | 0·58 (0·08–4·33) | 0·60 | 0·45 (0·04–4·89) | 0·51 |
| Calcineurin inhibition | ||||
| Cyclosporine | 1 (ref) | ·· | ·· | ·· |
| Tacrolimus | 0·70 (0·31–1·58) | 0·39 | ·· | ·· |
| Antiproliferative immunosuppression | ||||
| Azathioprine | 1 (ref) | ·· | 1 (ref) | ·· |
| Mycophenylate | 0·43 (0·18–0·99) | 0·049 | 0·30 (0·11–0·85) | 0·022 |
| None or held | 1·92 (0·77–4·82) | 0·16 | 2·24 (0·53–9·39) | 0·27 |
| Primary graft dysfunction immediately (<24 h) after transplant | ||||
| Grade 0 | 1 (ref) | ·· | 1 (ref) | ·· |
| Grade 1 | 0·82 (0·28–2·41) | 0·72 | 1·03 (0·28–3·83) | 0·96 |
| Grade 2 | 0·55 (0·17–1·74) | 0·31 | 0·40 (0·11–1·44) | 0·16 |
| Grade 3 | 1·09 (0·46–2·63) | 0·84 | 1·52 (0·57–4·11) | 0·40 |
| Cumulative A rejection score, per 1-point increase | 1·01 (0·40–2·54) | 0·98 | 0·53 (0·17–1·67) | 0·28 |
| Cumulative B rejection score, per 1-point increase | 0·57 (0·07–4·40) | 0·59 | 0·44 (0·04–4·34) | 0·48 |
| DSA present† | 1·33 (0·47–3·78) | 0·59 | 1·29 (0·40–4·15) | 0·67 |
| BALF neutrophil percentage, per 10% increase‡ | 1·03 (0·83–1·27) | 0·79 | ·· | ·· |
| BALF lymphocyte percentage, per 10% increase‡ | 1·25 (0·93–1·68) | 0·14 | ·· | ·· |
| BALF bacterial culture | ||||
| Negative; no growth | 1 (ref) | ·· | 1 (ref) | ·· |
| Oral flora | 1·53 (0·61–3·86) | 0·37 | 0·94 (0·34–2·60) | 0·91 |
| Positive; speciated result | 2·02 (0·62–6·61) | 0·25 | 0·73 (0·17–3·06) | 0·66 |
| Number of previous positive BALF bacterial cultures | ||||
| None | 1 (ref) | ·· | ·· | ·· |
| One | 0·50 (0·11–2·25) | 0·37 | ·· | ·· |
| Two or more | 1·29 (0·56–2·98) | 0·55 | ·· | ·· |
| History of community-acquired respiratory viral infection§ | 1·87 (0·56–6·18) | 0·31 | 0·72 (0·11–4·62) | 0·73 |
| History of CMV pneumonitis | 1·14 (0·34–3·75) | 0·84 | 1·82 (0·39–8·54) | 0·45 |
| Antibiotics in the 30 days before bronchoscopy | 0·75 (0·23–2·48) | 0·64 | ·· | ·· |
| Azithromycin for CLAD prevention | 0·81 (0·11–5·98) | 0·83 | ·· | ·· |
| Lung bacterial burden, per log10 increase¶ | 1·89 (1·30–2·75) | 0·0008 | 2·49 (1·38–4·48) | 0·0024 |
| Lung bacterial burden tertiles¶ | ||||
| Lowest bacterial burden tertile | 1 (ref) | ·· | 1 (ref) | ·· |
| Middle bacterial burden tertile | 4·06 (1·13–14·54) | 0·032 | 4·94 (1·25–19·42) | 0·022 |
| Highest bacterial burden tertile | 5·98 (1·73–20·68) | 0·0047 | 10·56 (2·53–44·08) | 0·0012 |
The multivariable model included known risk factors for CLAD and variables associated with either our primary outcome or bacterial burden in univariable analyses (appendix p 4). HR=hazard ratio. DSA=donor-specific antibodies. BALF=bronchoalveolar lavage fluid. CMV=cytomegalovirus. CLAD=chronic lung allograft dysfunction.
Calculated with Cox proportional hazards regression models.
64 patients had no DSA information available and were analysed as a unique category (not reported).
Five patients had no BALF cell count information available and were analysed as a unique category (not reported).
Among 55 patients without respiratory viral PCR results at the 1-year surveillance bronchoscopy, 53 had no evidence of a CARV within the first year and two had a previous CARV that cleared by 1 year; no patients with excluded or analysed as missing for this variable.
Distinct multivariable analyses were done for bacterial burden as a continuous variable and bacterial burden tertiles as categorical variables.