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“Crazy paving” on CT images refers to the superimposition of ground‐glass opacity and linear pattern resembling irregularly shaped paving stones. Initially, “crazy paving” was described as a pathognomonic sign of alveolar proteinosis. Subsequently, this pattern has been reported in a variety of disorders of the lung. We demonstrated CT images of lung adenocarcinoma demonstrating both solid and crazy‐paving appearances.

We report the first case of autoimmune pulmonary alveolar proteinosis (PAP) associated with and preceding myelodysplastic syndrome. A 74‐year‐old female with a history of polymyalgia rheumatica presented with six months history of progressive exertional breathlessness. Examination revealed bilateral chest crackles and exertional desaturation. A diagnosis of autoimmune PAP was made based on the presence of autoantibodies to granulocyte‐macrophage colony‐stimulating factor and characteristic findings on chest computed tomography, bronchoalveolar lavage, and transbronchial biopsies. Bilateral whole lung lavage was performed with prompt improvement in symptoms. Fourteen months later, she presented with new breathlessness and was diagnosed with myelodysplasia on bone marrow biopsy. No recurrence of alveolar proteinosis was detected. This case highlights the importance of follow‐up and screening of patients with autoimmune PAP for haematological conditions., We report the first case of autoimmune pulmonary alveolar proteinosis associated with and preceding myelodysplastic syndrome.

PAP is a rare disease characterized by the accumulation of surfactant materials in the alveolar spaces due to the imbalance of surfactant homeostasis (production and clearance). We herein report a case of an 8-year-old girl who developed PAP after BMT from her mother for the treatment of DBA. The anemia was improved by BMT; however, respiratory dysfunction due to graft-versus-host disease gradually progressed. She eventually underwent right single LDLLT from her mother when she was 14 years old. A pathological examination of the excised lung confirmed the finding of diffuse bronchiolitis obliterans and unexpectedly revealed widespread alveolar proteinosis. Interestingly, the GGO of her native left lung on chest X-ray was improved after LDLLT. We present the very unique clinical course of this patient and discuss the mechanisms underlying the development of PAP after BMT and its improvement after LDLLT from the same donor.

Occupational lung disease secondary to inhalation of silica particles is variable and potentially life-threatening. As the artificial stone industry has grown over the last two decades, the development of silicosis has been seen to accelerate and behave differently to chronic silicosis. In this case report, we present two patients who underwent lung transplantation for silicosis at the Alfred Hospital, both with predominantly artificial stone masonry exposure. We have identified the presence of both fibrotic/nodular silicosis and conspicuous alveolar proteinosis within the same lung parenchyma of both patients. We then demonstrate the radiological and histopathological correlates of disease; the first time this has been shown clearly in the literature.

Background and objective: The aim of the present study was to report the features of five patients with concurrent histopathological features of pulmonary alveolar proteinosis (PAP) and hypersensitivity pneumonitis (HP) and their high-resolution CT (HRCT) appearances. Methods: Patients with histopathological features of both HP and PAP on surgical lung biopsy referred for tertiary review were retrospectively identified. The pathology and HRCT images were semi-quantitatively scored to evaluate the relative contribution to HP and PAP. Results: Five patients had histopathological features of HP and PAP but had varied HRCT appearances. All had imaging features of PAP to a varying degree with two patients also showing characteristics of HP but three patients had ill-defined thickened interlobular septa, not typical of either disease. Conclusions: We describe the coexistence of PAP and HP in five patients and discuss possible linkages between these two distinct pathologies.

Mutations in the surfactant protein (SP)-B gene are responsible for SP-B deficiency in congenital alveolar proteinosis (CAP) (Nogee et al. J Clin Invest 1994: 93: 1860-1883; Lin et al. Mol Genet Metab 1998: 64: 25-35; Klein et al. Pediatrics 1998: 132: 244-248; Ballard et al. Pediatrics 1995: 96: 1046-1052). The multigenerational consanguineous pedigree under study does not carry any of the known mutations, although this pedigree had 14 infant deaths following respiratory distress at birth. Immunostaining of the lungs from three such infants revealed decreased or absent SP-B. By sequencing of SP-B exons, exon-intron junctions, and the 5' and 3' flanking regions, nine polymorphisms were found in this pedigree, but none of them could explain the observed SP-B deficiency. Further analysis of SP-B mRNA by reverse transcription-polymerase chain reaction from paraffin-embedded lung tissue of CAP patients showed that SP-B mRNA is not intact. Although the sequence of mRNA from exon 1-exon 7 and from exon 8-exon 10 could be amplified, the region between exons 7 and 8 could not. From fluorescence in situ hybridization of the short arm of chromosome 2p, only 2 signals were identified, eliminating the possibility of translocation as the cause of the SP-B mRNA aberrance. Although the nature of the genetic basis of SP-B deficiency in this family is currently unknown, the existence of aberrant SP-B mRNA may, at least in part, be responsible for the SP-B deficiency in this pedigree.

Pulmonary complications are frequently encountered in patients with hematological malignancy. The optimal therapeutic decision including open lung biopsy (OLB) for such patients is uncertain. We herein examine the clinical impact of OLB on these patients. Seven patients with progressively diffuse pulmonary infiltrates despite aggressive medical treatment were examined. The underlying diseases, prior treatment for presumptive pneumonia, the change in therapeutic approach after operation, and clinical outcome were reviewed retrospectively. Diffuse pulmonary infiltrates were caused by infection in two patients and by noninfectious etiology such as alveolar proteinosis, idiopathic interstitial pneumonitis, leukemic involvement, and drug-induced alveolar damage in the others. Four patients who had serious underlying hematologic diseases such as myelodysplastic syndrome, acute and chronic myeloid leukemia, and T cell lymphoma died. Three patients with acute lymphoid leukemia survived. In two of these three, change of therapeutic strategies after OLB was created for the survival. OLB in patients with hematological malignancy may be useful in selected patients with a treatable hematologic disease who have treatable underlying causes of the pulmonary infiltrate.

Congenital alveolar proteinosis due to surfactant protein B deficiency is an inherited disease which results in severe respiratory failure in term infants soon after birth. The pathophysiologic basis of this disease is now known to be an inability to synthesise adequate quantities of normally functioning surfactant protein B. We report a male infant with fatal respiratory failure of neonatal onset, and histopathological features typical of those seen in congenital alveolar proteinosis. Molecular analysis of genomic DNA revealed two mutations, the 'common' 121ins2 mutation in exon 4, and a novel 2bp frameshift mutation in exon 5. We believe this is the first Australian case of surfactant protein B deficiency confirmed by molecular analysis.

A 32-year-old Japanese man with chronic granulocytic leukemia died of respiratory failure. Autopsy revealed alveolar proteinosis and pulmonary fibrosis, complicated by disseminated atypical mycobacteriosis. Epithelial hyperplasia caused by busulfan therapy was probably responsible for the induction of excessive surfactant production, resulting in alveolar proteinosis, and the immunosuppressive state due to chronic granulocytic leukemia was probably related to the induction of disseminated atypical mycobacteriosis.

We report on the DNA-based prenatal diagnosis of congenital pulmonary alveolar proteinosis in a family in which alveolar proteinosis was associated with surfactant protein B (SP-B) deficiency. The parents had lost an eight-week-old female child due to this fatal disorder. The affected child was homozygous and both parents were heterozygous for a frame-shift mutation in codon 121 of the surfactant protein B gene (SFTP3-gene). Chorionic villus sampling (CVS) was performed in two subsequent pregnancies. DNA analysis revealed homozygosity for the codon 121 mutation in the first fetus, and the pregnancy was terminated. Homozygosity for the parental wild-type alleles was detected in the following prenatal diagnosis, and a healthy child has been born. DNA-based prenatal diagnosis of congenital alveolar proteinosis is simple, fast and reliable, and can be performed much earlier in pregnancy than any other method, e.g. the direct measurement of SP-B in amniotic fluid. In families with a term infant who dies of unexplained respiratory failure, genetic testing of the parents should be evaluated, since the presence of the codon 121 mutation enables prenatal diagnosis in later pregnancies.

A case of alveolar proteinosis is reported which was treated by lung lavage. The technique requires a Robertshaw double-lumen tube to isolate each lung. Initial ventilation with 100% oxygen removes lung nitrogen and the first 500 ml of saline occupies part of the functional reserve capacity and is not recovered. Lavage is then continued with 500-ml aliquots until the washings become clear. Monitoring the oxygen--haemoglobin saturation by ear-oximetry showed changes of between 15 and 20%, falling during suction and rising during infusion of lavage fluid. At the end of lavage, gas exchange is severely impaired by retained saline and a variable period of controlled ventilation may be required.

Summary A patient with alveolar proteinosis develqed unexpected cardiovascular instability after broncho-alveolar lavage. He had received two bolus doses of etomidate within an 18-hour period. Serum cortisol concentrations were low and hydrocortisone replacement therapy was necessary to restore arterial pressure. Implications for management of critically ill patients who receive bolus doses of etomidate are discussed.