Although pulmonary complications are frequent in patients suffering from hematological diseases, secondary pulmonary alveolar proteinosis is a very rare complication of myelofibrosis. We describe the case of a 65-year-old male patient treated by Ruxolitinib for myelofibrosis who developed a secondary pulmonary alveolar proteinosis complicated by a Mycobacterium avium infection. We believe that this respiratory complication might be related to the myelofibrosis and to the initiation of the Ruxolitinib according to its temporal relationship. Pulmonologists should be aware that respiratory symptoms in myelofibrosis patients taking Ruxolitinib may be related to pulmonary alveolar proteinosis.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a special clinical presentation mostly associated with autoimmune disorders. Here we report a rare case of PAP secondary to infection of Bacillus megaterium.
METHODS: A 58-year-old woman presented with intermittent cough and dyspnea for half a year. Chest CT scan showed \"crazy paving\" pattern. B. megaterium was identified by percutaneous CT-guided needle biopsy. She continuously received antimicrobial treatment since the diagnosis and follow-up examination suggested great improvement.
CONCLUSIONS: To our knowledge, this is the first case of B. megaterium infection presented with PAP pattern in healthy individuals. Attention should be paid on the secondary causes including rare pathogen infection when patients presented with PAP syndrome.

What is this summary about? This is a plain language summary of a late-stage clinical trial called IMPALA, originally reported in The New England Journal of Medicine. The IMPALA trial studied a drug called molgramostim nebulizer solution (molgramostim) to see how well it worked and how safe it was in patients with autoimmune pulmonary alveolar proteinosis (aPAP). Normally, tiny air sacs (alveoli) in the lungs are covered by a thin layer of an oily substance called surfactant that helps to keep them open. In aPAP, surfactant builds up and clogs alveoli making it difficult to breathe. Inhaled molgramostim helps to reduce the amount of surfactant clogging the alveoli.What were the results of the trial? After 24 weeks of treatment, patients who received molgramostim every day had better oxygen transfer into blood than patients who received an inactive substance (placebo). Patients’ sense of well-being and quality of life was improved more with daily molgramostim than placebo. The amount of surfactant in the lungs measured using scans and the number of whole-lung lavages (lung washes) patients required were lower with daily molgramostim than placebo. The number of medical problems (adverse events) was similar in patients who received molgramostim and placebo except for chest pain, which was more common with molgramostim.What do the results of the trial mean? The IMPALA trial demonstrated that molgramostim is a promising treatment option for people with aPAP.

Pulmonary alveolar proteinosis (PAP) is a syndrome that results from the accumulation of lipoproteinaceous material in the alveolar space. According to the underlying pathogenetic mechanisms, three different forms have been identified, namely primary, secondary and congenital. Primary PAP is caused by disruption of granulocyte-macrophage colony-stimulating factor (GM-CSF) signalling due to the presence of neutralising autoantibodies (autoimmune PAP) or GM-CSF receptor genetic defects (hereditary PAP), which results in dysfunctional alveolar macrophages with reduced phagocytic clearance of particles, cholesterol and surfactant. The serum level of GM-CSF autoantibody is the only disease-specific biomarker of autoimmune PAP, although it does not correlate with disease severity. In PAP patients with normal serum GM-CSF autoantibody levels, elevated serum GM-CSF levels is highly suspicious for hereditary PAP. Several biomarkers have been correlated with disease severity, although they are not specific for PAP. These include lactate dehydrogenase, cytokeratin 19 fragment 21.1, carcinoembryonic antigen, neuron-specific enolase, surfactant proteins, Krebs von Lungen 6, chitinase-3-like protein 1 and monocyte chemotactic proteins. Finally, increased awareness of the disease mechanisms has led to the development of pathogenesis-based treatments, such as GM-CSF augmentation and cholesterol-targeting therapies.

OBJECTIVE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are implicated in the pathogenesis of Cryptococcus gattii (C. gattii) infection and pulmonary alveolar proteinosis (PAP). Their presence has also been noted in nocardiosis cases, particularly those with disseminated disease. This study delineates a case series characterizing clinical features and specificity of anti-GM-CSF Abs in nocardiosis patients.
METHODS: In this study, eight patients were recruited to determine the presence or absence of anti-GM-CSF Abs. In addition to the detailed description of the clinical course, we thoroughly investigated the autoantibodies regarding the characteristics, isotypes, subclasses, titers, and neutralizing capacities by utilizing the plasma samples from patients.
RESULTS: Of eight patients, five tested positive for anti-GM-CSF Abs, all with central nervous system (CNS) involvement; patients negative for these antibodies did not develop CNS nocardiosis. Distinct from previously documented cases, none of our patients with anti-GM-CSF Abs exhibited PAP symptoms. The titer and neutralizing activity of anti-GM-CSF Abs in our cohort did not significantly deviate from those found in C. gattii cryptococcosis and PAP patients. Uniquely, one individual (Patient 3) showed a minimal titer and neutralizing action of anti-GM-CSF Abs, with no relation to disease severity. Moreover, IgM autoantibodies were notably present in all CNS nocardiosis cases investigated.
CONCLUSIONS: The presence of anti-GM-CSF Abs suggests an intrinsic immunodeficiency predisposing individuals toward CNS nocardiosis. The presence of anti-GM-CSF Abs helps to elucidate vulnerability to CNS nocardiosis, even with low titer of autoantibodies. Consequently, systematic screening for anti-GM-CSF Abs should be considered a crucial diagnostic step for nocardiosis patients.

A rare and challenging case of a preterm neonate with clinical and radiological signs of respiratory distress syndrome (RDS) since the first hour of life but was refractory to its standard treatment regimes like surfactant therapy and ventilation. Postmortem lung biopsy led us to the diagnosis of congenital pulmonary alveolar proteinosis (PAP). It occurs due to the aggregation of abnormal surfactant proteins and lipids in the alveoli, which hampers gas diffusion across the alveoli. It presents as respiratory distress at birth, and its diagnosis is often missed due to its resemblance with RDS. Although the exact etiology remains elusive, mutations in genes encoding surfactant and granulocyte-macrophage colony-stimulating factor (GM-CSF) pathway components have been implicated in the pathogenesis of PAP. Treatment options are limited and only supportive. Among all these, whole-lung lavage is the most widely used management modality but with limited success in neonates.

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Pulmonary alveolar proteinosis (PAP) is an ultra-rare disease caused by impaired pulmonary surfactant clearance due to the dysfunction of alveolar macrophages or their signaling pathways. PAP is categorized into autoimmune, congenital, and secondary PAP, with autoimmune PAP being the most prevalent. This article aims to present a comprehensive review of PAP classification, pathogenesis, clinical presentation, diagnostics, and treatment. The literature search was conducted using the PubMed database and a total of 67 articles were selected. The PAP diagnosis is usually based on clinical symptoms, radiological imaging, and bronchoalveolar lavage, with additional GM-CSF antibody tests. The gold standard for PAP treatment is whole-lung lavage. This review presents a summary of the most recent findings concerning pulmonary alveolar proteinosis, pointing out specific features that require further investigation.

UNASSIGNED: Lysinuric protein intolerance (LPI) is a rare genetic disorder caused by mutations in the solute carrier family 7A member 7 (SLC7A7) gene.
UNASSIGNED: We presented two siblings with LPI, carrying novel mutations of c.776delT (p.L259Rfs*18) and c.155G>T (p.G52V) in SLC7A7. The younger sibling, preferring protein-rich foods, showed severe symptoms, including alveolar proteinosis, macrophage activation syndrome, severe diarrhea, and disturbance of consciousness with involuntary movements. In contrast, the elder sibling only had mild symptoms, likely due to aversion to protein-rich food since toddler age.
UNASSIGNED: LPI is a congenital genetic metabolic disease with multi-system involvement. Initiating appropriate protein-restricted diet therapy as soon as possible could help prevent the progression of LPI.

Secondary pulmonary alveolar proteinosis (SPAP) is one of the diffuse parenchymal lung diseases, and the utility and safety of transbronchial lung cryobiopsy (TBLC) for diagnosing SPAP are unknown. A case of SPAP diagnosed by TBLC is presented. Specimens that were useful for diagnosis were collected, and there was no adverse event following TBLC. The usefulness of TBLC for interstitial lung disease has been widely reported, but there are few reports of SPAP. We present the clinical course of TBLC in the diagnosis of SPAP.