Adult case reports and series | | | | | |
SFTPC p.I73T | Adult with CPFE | Prednisone | No effect | No effect | [55] |
SFTPA2 p.G231V | 1 adult with hypersensitivity pneumonitis | Prednisone and avoidance of birds | Improvement | 1 improvement/1 no effect | [7] |
1 adult with pulmonary fibrosis and bronchoalveolar carcinoma | Prednisone | No effect |
ABCA3 p.G964D | Adult with pulmonary fibrosis | Antibiotics | No effect | Stabilisation | [10] |
Prednisone and azithromycin | Stabilisation |
ABCA3 p.G964D | Adult with restrictive lung disease | Steroids and azithromycin | (Short-term) improvement | Stabilisation | [85] |
HPS# | Adult with HPS | Antibiotics and oxygen inhalation | No effect | No effect | [92] |
HPS1 IVS5+5 G>A | Adult with HPS | Prednisolone, cyclosporine A | No effect | | [91] |
+ pirfenidone | Short-term stabilisation | Short-term stabilisation |
HPS4 p.Q620X | Adult with HPS | Corticosteroids, pirfenidone | Stabilisation | Stabilisation | [90] |
HPS1 p.L668P | Adult with HPS | Prednisolone, pirfenidone, azathioprine | No effect | No effect | [93] |
HPS# | Adult with HPS | Oral corticosteroids | No effect | No effect | [94] |
HPS4 p.685delC | Adult with HPS | High-dose steroids and azathioprine | No effect | No effect | [95] |
HPS# | Adult with HPS and pulmonary sarcoidosis | Prednisone | Improvement | Improvement | [89] |
HPS# | Adult with HPS | Prednisolone and pirfenidone | No effect | No effect | [96] |
Paediatric case reports/series with SFTPC mutations | | | | | |
SFTPC p.I73T p.I38F, p.V39L | 4 children with DIP, 1 child with chronic interstitial pneumonitis (p.V39L) | 1/5 systemic steroids | No effect | 2 short-term improvement/3 improvement | [36] |
5/5 hydroxychloroquine | 2 short-term improvement, 3 improvement |
SFTPC p.A116D | Child with NSIP | Hydroxychloroquine and supplemental oxygen | Improvement | Improvement | [37] |
SFTPC p.I73T | Child with ILD | Corticosteroids and supplemental oxygen | Improvement | Improvement | [55] |
SFTPC c.460+1 G → A | Child with cellular or NSIP | Corticosteroids and supplemental oxygen | Improvement | Improvement | [5] |
SFTPC p.I73T | 5 children with chronic ILD | 5/5 methylprednisolone, 4/5 hydroxychloroquine, 5/5 supplemental oxygen | 5 improvement | 5 improvement | [38] |
Different SFTPC BRICHOS/non-BRICHOS | 17 children with ILD (NSIP, PAP or DIP) | 14/17 hydroxychloroquine | 12/14 improvement 2/14 no effect | 7 improvement/7 stabilisation/3 no effect | [39] |
15/17 systemic steroids | 14/15 improvement 1/15 no effect |
7/17 surfactant | 2/7 improvement, 5/7 no effect |
3/17 colchicine | 3 no effect |
SFTPC 14 non-BRICHOS, 6 BRICHOS | 22 children with chronic ILD at diagnosis | 18/22 methylprednisolone, 11/22 hydroxychloroquine, 5/22 azithromycin, 20/22 supplemental oxygen | 6/22 no effect, 16/22 improvement | 16 improvement/6 no effect | [40] |
SFTPC p.G97S | Child with CPI pattern with globular alveolar proteinosis | Home ventilator support, oxygen, pulse methylprednisolone, azithromycin, hydroxychloroquine | Improvement | Improvement | [41] |
SFTPC p.I73T, p.I38F | 2 children with CPI | Hydroxychloroquine, prednisone, ranitidine, TMP-SMX; 2 months after therapy began, pulse therapy of methylprednisolone; later, hydroxychloroquine alone | 2 improvement | 2 improvement | [42] |
SFTPC p.I73T | Child with CPI, pneumatoceles after biopsy | Methylprednisolone, hydroxychloroquine, azithromycin | Improvement | Improvement | [43] |
SFTPC p.I73T | Child with ILD | Hydroxychloroquine, oxygen supplementation | Improvement | 1 improvement/1 stabilisation/1 no effect | [44] |
Child with ARDS/DIP | Supplemental oxygen and steroids | No effect |
Steroids pulse therapy | Short-term improvement |
Hydroxychloroquine | Improvement |
Hydroxychloroquine replaced by azithromycin | Stabilisation |
Child with DIP | Hydroxychloroquine and steroids | No effect |
SFTPC p.I73T | Child with chILD | Bronchodilators, inhaled corticosteroids and antileukotrienes, azathioprine, hydroxychloroquine and i.v. immunoglobulins, exogenous surfactant | No effect | No effect | [52] |
SFTPC p.I73T | Child with PAP and NSIP | Supplemental oxygen, whole-lung lavages, systemic corticosteroids and azathioprine | Short-term improvement | Short-term improvement | [45] |
Additional corticosteroid pulse therapy plus azathioprine | No effect |
SFTPC Δexon 4 | Child with respiratory distress | Oral and i.v. corticosteroids, hydroxychloroquine, supplemental oxygen | Improvement | Improvement | [51] |
SFTPC p.E66K, p.I73T, p.V102M, p.A155P | 8 children with idiopathic diffuse lung diseases | 2 children supplemental oxygen, pulse steroids and hydroxychloroquine | 2 limited effect | 2 limited effect/6 stabilisation | [46] |
Supplemental oxygen, pulse steroids, hydroxychloroquine | Stabilisation |
Supplemental oxygen, hydroxychloroquine | Stabilisation |
Supplemental oxygen, steroids, hydroxychloroquine, azithromycin | Stabilisation |
Supplemental oxygen, pulse steroids, hydroxychloroquine | Stabilisation |
Supplemental oxygen, pulse steroids, bronchodilators, antibiotics | Stabilisation |
Steroids, supplemental oxygen | Stabilisation |
SFTPC p.L188Q | 2 children with respiratory distress (NSIP-like pattern) | Methylprednisolone and hydroxychloroquine | 2 no effect | 2 no effect | [53] |
SFTPC# | Child with CPI | Corticosteroids, hydroxychloroquine and continuous oxygen | Short-term improvement | Short-term improvement | [47] |
SFTPC p.I73T | Child with NSIP/PAP | Supplemental oxygen, antibiotics and oral corticosteroids | No effect | No effect | [54] |
SFTPC p.I73T | Child with PAP/ILD | Whole-lung lavages, systemic corticosteroids and azathioprine | Improvement | Improvement | [48] |
SFTPC p.G182R, p.L188Q, p.C189W | 1 child with PAP/NSIP | Clearance, steroids, hydroxychloroquine, mechanical ventilation | Improvement | 3 improvement | [49] |
1 child with respiratory failure | Clearance, steroids, azathioprine, mechanical ventilation | Improvement |
1 child with respiratory failure | Steroids, azithromycin, hydroxychloroquine, mechanical ventilation | Improvement |
SFTPC p.L81V | Child with surfactant protein C deficiency | Hydroxychloroquine, oxygen therapy | Improvement | Improvement | [87] |
SFTPC# | Child with NSIP | Systemic steroids, azathioprine, hydroxychloroquine | Improvement | Improvement | [88] |
Different SFTPC mutations | 15 children with interstitial chronic lung disease | All methylprednisolone 5/15 azithromycin 8/15 hydroxychloroquine | 11 no effect/4 improvement | 11 no effect/4 improvement | [50] |
Paediatric case reports/series with ABCA3 mutations | | | | | |
ABCA3#/SFTPC | Child with DPLD/surfactant dysfunction | Surfactant | Improvement | 2 short-term improvement/1 no effect | [88] |
Systemic steroids | No effect |
ABCA3# | Child with CPI | Systemic steroids, surfactant | Improvement |
Chloroquine | No effect |
Child with DIP | Systemic steroids, hydroxychloroquine | No effect |
ABCA3 c.358_359del | Child with ABCA3 deficiency | Methylprednisolone, oxygen therapy | Limited effect | Limited effect | [87] |
ABCA3 p.W1148X and p.T1114A | Child with PAP-like features | Methylprednisolone, antibiotics, antivirals and antifungals, oxygen, mechanical ventilation | No effect | Improvement | [76] |
BAL with bovine surfactant | Improvement |
Hydroxychloroquine | Improvement |
ABCA3 p.G964D | Child with (possible) IPF | Prednisone and macrolides | Improvement | Improvement | [10] |
ABCA3 p.A307V | Child with respiratory distress | Dexamethasone and surfactant, CPAP | Short-term improvement | Improvement | [75] |
Methylprednisolone, azithromycin, hydroxychloroquine | Improvement |
ABCA3 p.Y1515X | Child with RDS | Pulse steroids, antibiotics | No effect | No effect | [77] |
ABCA3 p.R194G and V1615GfsX15 | 2 children with IRDS | CPAP, corticosteroids and hydroxychloroquine | 2 limited effect | 2 limited effect | [78] |
ABCA3 p.D253H | Child with DPLD | Methylprednisolone, oral prednisone, oxygen therapy | No effect | Improvement | [74] |
Azithromycin | Improvement |
ABCA3 p.R280C and p.E690G | Child with DIP | Oxygen supplementation, surfactant therapy, corticosteroids | No effect | Improvement | [73] |
Hydroxychloroquine | Improvement |
ABCA3 p.D507del CA Ter 508, p.D696N | Child with DIP | Dexamethasone, supplemental oxygen, surfactant therapy | Short-term improvement | Improvement | [72] |
Methylprednisolone, azithromycin, hydroxychloroquine | Improvement |
ABCA3 p.K914R, p.L1238_E1239insGG | Child with ILD | Methylprednisolone, antibiotics | Limited effect | Improvement | [71] |
+ hydroxychloroquine | Improvement |
ABCA3 c.59G>T and c.2646_2647insC | Child with severe RDS | Home ventilator, methylprednisolone, hydroxychloroquine, azithromycin | Improvement | Improvement | [70] |
ABCA3 p.H778R, p.L1252P | Child with DIP-like pattern | Methylprednisolone, prednisone and hydroxychloroquine, clarithromycin | Improvement | Improvement | [69] |
Different ABCA3 mutations | 9 children with PAP pattern, DIP pattern and NSIP pattern | All corticosteroids, 7/9 hydroxychloroquine | 4 no effect, 2 stabilisation, 3 improvement | 4 no effect, 2 stabilisation, 3 improvement | [68] |
ABCA3, p.L798P, p.R1612P | Child with DIP | Antibiotics, supplemental oxygen, exogenous surfactant, methylprednisolone, hydroxychloroquine | No effect | No effect | [79] |
ABCA3 p.R1561Stop | Child with respiratory distress with cyanosis | Antibiotics, surfactant, dexamethasone, inhaled nitric oxide, methylprednisolone, hydroxychloroquine | Short-term improvement | Short-term improvement | [67] |
ABCA3 large deletion exon 2–5 | Child with IRDS | N-CPAP, surfactant therapy, dexamethasone | No effect | No effect | [80] |
ABCA3 ΔF1203 and c.1375ins15 | Child with IRDS | Supplemental oxygen and systemic corticosteroids and diuretics | No effect | No effect | [81] |
ABCA3 p.R20L and c.4483del25 | Child with ILD | Prednisolone and supplemental oxygen | No effect | No effect | [82] |
ABCA3 heterozygous p.E292V | Child with cerebropulmonary dysgenetic syndrome | CPAP, mechanical ventilation and antibiotics | No effect | No effect | [84] |
ABCA3 p.S1116F | Child with RDS | Supplemental oxygen, mechanical ventilation, exogenous surfactant, antibiotics and inhaled nitric oxide | No effect | No effect | [83] |
ABCA3 mutation# | 19 children (14 RDS, 4 RDS/PAP, 1 PAP) | 16/19 surfactant | 7 no effect, 9 improvement/short-term improvement | 29 no effect/3 improvement/3 stabilisation | [85] |
19/19 systemic steroids | 14 no effect, 5 improvement/short-term improvement |
9/19 hydroxychloroquine | 5 no effect, 4 improvement/short-term improvement |
2/19 azithromycin | 2 no effect |
Heterozygous ABCA3 mutation# | 16 children (9 with RDS, 4 with RDS/PAP, 1 PAP, 2 chILD) | 12/16 surfactant | 8 no effect, 4 improvement/short term improvement |
12/16 systemic steroids | 8 no effect, 4 improvement/short-term improvement |
8/16 hydroxychloroquine | 3 no effect, 5 improvement/short-term improvement |
ABCA3 p.M1227R and Ins1510fs/ter1519 | Child with DIP | Macrolides, dexamethasone, mechanical ventilation | No effect | Short-term improvement | [66] |
Surfactant | Short-term improvement |
ABCA3 heterozygous R288K (7 patients) p.R43L, R288K + c.4751delT (1 patient), R288K, P766S (heterozygous, 1 patient), R288K, S693L (heterozygous, 1 patient), R288K, Q215K (1 patient) | 11 children with ILD | 5/11 prednisolone, surfactant, oxygen or corticosteroids | No effect | 5 no effect/6 improvement | [65] |
6/11 oxygen, aspirin, surfactant, dexamethasone, montelukast, salbutamol, steroids, hydroxychloroquine, azathioprine, azithromycin or antibiotics | Improvement | | |
Paediatric case report with AP3B1 mutation | | | | | |
AP3B1 p.R509X and p.E659X | Child with HPS2 | Oxygen, systemic corticosteroids, G-CSF | Stabilisation | Stabilisation | [13] |
Clinical trials | | | | | |
HPS1¶ | 21 adults with HPS | 11 treated with pirfenidone, 10 placebo | Pirfenidone superior to placebo: ΔFVC of 0.46% per month (p=0.587) Restricted group including only patients with initial FVC values >50% pred: difference in pulmonary function ∼0.7% per month (p=0.02) | [97] |
HPS1 or 4+ | 35 adults with HPS | 23 treated with pirfenidone, 12 placebo | No statistically significant difference in lung function | [98] |