TABLE 1.
Presentation and treatment of four children with autoimmune pulmonary alveolar proteinosis (PAP)
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | |
| Age at presentation | 14 years | 14 years | 10 years | 15 years |
| Sex | Female | Male | Female | Male |
| Age at last follow-up | 14 years, 8 months | 16 years | 10 years, 6 months | 17 years |
| Previous history | Progressive dyspnoea on exertion for 7 months, two episodes of presumptive “community-acquired pneumonia” with fever, parenchymal lung infiltrates and dyspnoea during the past 18 months | Progressive dyspnoea with exercise for 1.5 years, weight loss, no appetite | No previous respiratory complaints. For 1 year, progressive dyspnoea on exertion, dry cough starting with a lower respiratory tract infection with fever over 2 weeks. Weight loss (3–4 kg). For 6 months, inhaled steroids, long-acting β-agonists | No previous relevant respiratory or other symptoms 3 months of progressive asthenia (very low weight: body mass index 15 kg·m−2; <3rd percentile), dry cough and dyspnoea |
| Initial presentation | 37.9°C, progressive dyspnoea, SpO2 89% in ambient air at rest, 94% on 4 L·min−1 oxygen, 25 breaths·min−1, expiratory crackles | No fever, no infections, pale, acrocyanosis, SpO2 at rest 88%, with slight movements <85% | No fever, no infections, pale, tachydyspnoea, SpO2 89% in ambient air at rest, inspiratory crackles | No fever, significant retractions, tachypnoea, inspiratory crackles SpO2 <89% |
| CT scan with crazy-paving pattern | Yes | Yes | Yes | Yes |
| BAL with milky appearance and cytology with acellular debris, no pathogenic organisms | Yes | Yes | Yes | Yes |
| Anti-GM-CSF antibody level (µg·mL−1) (reference <3 µg·mL−1) | 25.5 | 21.2 | Positive (Berlin and Hannover, Germany; not quantified) | Highly positive (Cambridge, UK; not quantified) |
| LDH (U·mL−1) at diagnosis (fold upper limit) | 1.6 | 1.3 | 0.9 | 0.5 |
| FVC (% pred) initial/last | 50/60 | 35/32 | 16.5/35 | 32/28 |
| DLCO (% pred) | 31 | Not done | Not done (55.3 after first WLL) | 20.4 |
| SARS-CoV-2 PCR test | Negative | Severe COVID-19 at age 15.3 years; 6 days hospitalisation, dexamethasone, 5 days NIV, increased oxygen need | Negative | Not done |
| SARS-CoV-2 serum antibody level (U·mL−1) | Not done | 228 (ref. <0.8) | Not done | Not done |
| WLL number (time period) | None | 13 (within 1 year) | 3 (within 5 months) | 6 (within 8 months) prior to rituximab/plasmapheresis over 1 month, followed by 1 WLL after 8 months |
| Inhaled GM-CSF (dose, duration) | Sargramostim (Leukine) 250 μg daily via an LC-STAR nebuliser with a manual interrupter valve connected to a PARI Turbo BOY compressor | Limited approval by insurance after 1 year of application and a court hearing | Sargramostim (Leukine) 250 μg daily via an e-flow nebuliser | Not available |
| Plasmapheresis-scheme, rituximab | Not done | Not done | Not done | 10 sessions of plasmapheresis followed by two doses of rituximab 375 mg·m−2 per dose; clinical improvement with less dyspnoea and need of oxygen |
| Overall outcome of PAP | Gradual improvement, complete remission of respiratory failure at rest at the end of the first month of treatment. Treatment was tapered to 4 days on, 1 day off at 3 months of further improvement. At 4 months after treatment initiation, CT of the chest demonstrated amelioration of the radiological findings and PFTs showed an increase of FVC to 58% predicted and DLCO to 49% predicted | With monthly WLL, just stable; deterioration to baseline before next WLL | Improved after first lung lavage (no oxygen dependency since then) and initiation of GM-CSF inhalation. No dyspnoea at rest or low physical activity, but no reconstitution of lung function since first WLL | WLL insufficiently treating respiratory failure; invasive off-label plasmapheresis and rituximab resulted in less dyspnoea, need of oxygen and WLL. CT and lung function improved, but did not normalise |
CT: computed tomography; BAL: bronchoalveolar lavage; GM-CSF: granulocyte–macrophage colony-stimulating factor; LDH: lactate dehydrogenase; FVC: forced vital capacity; DLCO: diffusing capacity of the lung for carbon monoxide; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; WLL: whole-lung lavage; SpO2: peripheral oxygen saturation; COVID-19: coronavirus disease 2019; NIV: noninvasive ventilation; PFT: pulmonary function test.