Table 2.
Patients with DAH, no plausible cause identified (“idiopathic pulmonary hemorrhage”, IPH; n = 34): Suggested disease entities, observation time, outcome and performed diagnostics.
| Number of performed diagnostic tests/ missing diagnostic tests/ tests with pathological results respectively positive findings for pulmonary hemorrhage | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Suggested disease entity | Observation time (years; mean (min/ max)) | Long-term course (healthy/ sick-better/ sick-same/ sick-worse/ dead) | Autoantibodies ANA/ ANCA (except tTG- autoantibodies) | tTG-auto-antibodies | Screening for immunodeficiency | Chest CT scan | Bronchoscopy and bronchoalveolar lavage | Lung biopsy | Targeted genetic testing for COPA-mutation (exon 8,9) |
| IPH associated with autoimmune features (n = 9) | 3.8 (0/ 10.7) | 3/ 2/ 1/ 2/ 1 (9y) | 9/ 0/ 9 | 5/ 4/ 1** | 8/ 1/ 1 | 9/ 0/ 9 | 5/ 4/ 5 | 4/ 5/ 4 | 6, +1 WES/ 2/ 0 |
| IPH associated with eosinophilia (n = 5) | 3.2 (0/ 6.7) | 3/ 0/ 1/ 1/ 0 | 5/ 0/ 0 | 3/ 2/ 0 | 5/ 0/ 0 | 5/ 0/ 5 | 4/ 1/ 4 | 1/ 4/ 1 | 4/ 1/ 0 |
| IPH associated with renal disease (n = 3) | 4.2 (2.1/ 7.2) | 0/ 2/ 0/ 1/ 0 | 3/ 0/ 1 | 1/ 2/ 0 | 3/ 0/ 0 | 3/ 0/ 3 | 3/ 0/ 2 | 1/ 2/ 1 | 2, +1 WES/ 0/ 0 |
| IPH associated with multi-organ involvement, suspected undetermined systemic disease (n = 3) | 2 (0.4/ 1.1) | 0/ 2/ 0/ 1/ 0 | 2/ 1/ 0 | 0/ 3/ 0 | 3/ 0/ 1 | 3/ 0/ 3 | 3/ 0/ 3 | 2/ 1/ 2 | 1/ 2/ 0 |
| IPH, no further classification (n = 14) | 4.4 (0.3/ 17.7) | 4/ 7/ 2/ 1/ 0 | 10/ 1, 3*/ 0 | 4/ 10/ 0 | 13/ 1/ 1 | 12/ 2/ 12 | 13/ 1/ 12 | 4/ 10/ 4 | 8, +2 WES/ 4/ 0 |
| All (n = 34) | 4.3 (0/ 17.7) | 10/ 13/ 4/ 6/ 1 | 29/ 2, 3*/ 10 | 13/ 21/ 1 | 32/ 2/ 3 | 32/ 2/ 34 | 28/ 6/ 26 | 12/ 22/ 12 | 25/ 9/ 0 |
| Missing diagnostics (%) | 15 % | 62 % | 6 % | 6 % | 18 % | 65 % | 26 % | ||
incomplete: either ANA or ANCA missing;
at this time, the patient had a normal gut biopsy under gluten-containing diet
WES: whole exome sequencing; tTG: tissues transglutaminase
“sick-better” is defined as signs or symptoms of the disease having weakened in intensity and/or number, ”sick-same” is defined as signs or symptoms with same intensity and number, “sick-worse” is defined as signs or symptom having increased in intensity and/ or number compared to baseline (52).
Note: Patients showed elevated ANCAs in only two cases in the cluster of IPH associated with autoimmune features (isolated elevation of ANCAs) and in one case in the cluster of IPH associated with renal disease (elevation of ANCAs as well as ANAs).